Results of resection of gastric cancer with distant metastases

BACKGROUND/AIMS: The present study was carried out in order to examine the outcome of resection in cases of gastric cancer with distant metastases. METHODOLOGY: The survival rates of two hundred and eighty-one patients who had undergone resection for primary carcinomas of the stomach, and who had distant metastases according to the TNM classification, were studied. RESULTS: The 5-year survival rates for patients with metastasis to the peritoneum or group 3 nodes were 8.9% and 15.3% respectively and were significantly higher than the survival rates for patients with metastasis to the liver (0%), to group 4 nodes (2.2%) or to more than one site among the liver, lymph nodes and peritoneum (3.5%). Moreover, the 5-year survival rates for patients with metastasis to the peritoneum and N3 nodes increased significantly to 29.4% and 24.2%, respectively, when curative surgery was performed. CONCLUSIONS: The findings of the present study suggests that metastases to the adjacent peritoneum or group 3 nodes have a greater chance of being cured using radical surgery, and that gastrectomy with extended lymphadenectomy (D2-D3) may be used for advanced gastric cancer if there is no gross evidence of metastasis to the distant peritoneum, liver or group 4 nodes.     

Modulation of cellular adhesion in bovine brain microvessel endothelial cells by a decapeptide

Immunohistochemical assessment was made of nm23 protein expression in pulmonary adenocarcinoma. Of the 147 adenocarcinomas 67% (99/147) were weakly and 33% (48/147) strongly positive for nm23 protein. nm23 protein expression in primary tumors was shown to correlate inversely with advancing pathologic stage and the degree of metastasis in regional lymph nodes (P < 0.05). The staining of tumors without nodal metastasis was more intense than with nodal metastasis (P < 0.02). Nodal metastasis was seen in 37% (55/147) cases examined. The immunoreactivity to nm23 protein in tumor cells of nodal metastasis was essentially the same as in those of primary tumors (P < 0.01). Significant correlation between patient prognosis and immunoreactivity for nm23 in primary tumors (P < 0.05) was demonstrated. But none could be found between immunoreactivity and other parameters such as histologic grading, distant metastasis, tumor size or disease-free survival. Neither was there any significant correlation between pathologic parameters examined and the expression of nm23 in any histologic subtype. Multivariate analysis using Cox's proportional hazards regression model with five variables indicated nm23 and lymph node metastasis to contribute to overall patient survival. Based on risk ratio disadvantageous state/advantageous states, the gravity of prognostic factors was assessed for lymph node metastasis as 9.25, nm23 expression as 2.06, distant metastasis as 1.23, pathologic stage as 0.78 and tumor size as 0.77. The results suggested that in pulmonary adenocarcinoma a reduced expression of nm23 protein was associated with lymph node metastasis and poor patient survival.     

T1a and T1b breast cancer: a twelve-year experience

To understand the prevalence of axillary node metastasis and survival of patients with T1a and T1b breast cancers, we reviewed the experience at a large community hospital. All patients in the William Beaumont Hospital tumor registry with breast cancer treated between January 1983 and November 1995 were evaluated for tumor size, age, cell type, and the presence or absence of axillary node disease. Long-term survival was evaluated in patients treated between 1983 and 1992. The patients were defined as premenopausal or postmenopausal based on age (49 years or less, premenopausal; 50 years or greater, postmenopausal). Of the 4590 patients treated for breast cancer from 1983 to 1995, 915 had tumors 1.0 cm or less in size. Of 181 patients who had T1a cancer, 27 were premenopausal, and 154 were postmenopausal. Twenty-three premenopausal patients had axillary lymph nodes examined, two (8.7%) had histologically positive lymph nodes. Of 118 postmenopausal patients who had axillary nodes examined, six (5.1%) had positive lymph nodes. In those with T1b tumors, 130 patients were premenopausal; 604 patients were postmenopausal. Of these, 119 premenopausal patients had axillary nodes examined, and 29 (24.4%) had positive lymph nodes. Of 464 postmenopausal patients who had axillary nodes examined, 66 (14.2%) had positive nodes. The overall, disease-free, and tumor-specific survival rates for patients with T1a tumors were 93.8, 87.5, and 93.8 per cent (premenopausal) and 86.2, 95.4, and 95.4 per cent (postmenopausal), respectively. These survival rates for patients with T1b tumors were 87.8, 87.8, and 91.1 per cent (premenopausal) and 82.9, 88.5, and 92.9 per cent (postmenopausal), respectively. Premenopausal T1b patients had a higher rate of nodal involvement than postmenopausal T1b patients (P = 0.011). Postmenopausal T1b patients had a higher nodal metastasis rate than postmenopausal T1a patients (P = 0.01). T1b patients had a higher rate of axillary involvement than did T1a patients (P = 0.0018). Based on the rate of axillary lymph node metastasis and survival statistics, there may be a role for axillary node dissection in select patients with tumors less than 1.0 cm. in size.     

Melanoma of unknown primary site: presentation, treatment, and prognosis--a single institution study. University of Pennsylvania Pigmented Lesion Study Group

BACKGROUND: A retrospective analysis of 40 patients diagnosed with melanoma of unknown primary site (MUP) was undertaken to analyze the etiology and clinical behavior of this presentation. METHODS: The patient records were located by a computer search of the Pigmented Lesion Clinic data base at the University of Pennsylvania. With the Cox proportional hazards model, the survival of the MUP patients with lymph node presentation was compared with that of patients with lymph node disease and a known concurrent primary melanoma. RESULTS: Sixty-five percent of the patients presented with lymph node metastasis only, 28% presented with visceral lesions, and 8% presented with subcutaneous nodules. The prevalence of dysplastic nevi was 22.5%. The overall 4-year survival rate for the 40 MUP patients was 55% +/- 9%. The 4-year survival (57% +/- 12%) of patients with lymph node presentation was compared with that of patients presenting with lymph node disease and a known concurrent primary melanoma (19 +/- 6%). Survival was significantly different between the groups (P = 0.008). This survival difference remained significant (P = 0.02) even after adjustments for number of positive lymph nodes, year of diagnosis, and age at diagnosis. CONCLUSIONS: This analysis revealed that MUP patients with lymph node metastasis survived significantly longer than patients diagnosed with lymph node metastasis concurrent with a known cutaneous primary melanoma. The prevalence of dysplastic nevi in the MUP patient series was intermediate between that reported among primary melanoma patients and that reported among population controls, suggesting the likelihood of a primary cutaneous origin for the metastatic melanoma.     

The value of lymphography for the TNM classification of renal carcinoma

Preoperative lymphography is a basic condition for uniform tumor classification of renal carcinoma, according to the T, N and M categories. The comparison of 148 lymphographic findings with 170 intraoperative and histopathological lymph node results showed a satisfactory correlation. The total frequency of lymph node metastasis was of 21.6%. Carcinomas with positive lymph nodes showed a significant increase of far distant metastasis up to 50%. Lymph node metastases have to be considered in 10% of all carcinomas of the T1 and T2 categories and in 15.5% of the cases with unclear preoperative lymphographic diagnosis. These results point out the necessity of a radical lymphadenectomy in all T categories.     

Dural puncture and activated protein C resistance: risk factors for cerebral venous sinus thrombosis

BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS: Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer specific survival was 94.0% for patients without lymph node metastasis, and 51.0% for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was -0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS: The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes.     

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.     

Lymph node harvest reporting in patients with carcinoma of the large bowel: a French population-based study

BACKGROUND: In patients with resected colorectal carcinoma, lymph node involvement has particular importance for patient prognosis and adjuvant therapy. The network of French cancer registries (FRANCIM) established a study aimed at analyzing the validity of lymph node harvest reporting in a population-based sample. METHODS: The study population was comprised of 1081 resected tumors without distant visceral metastasis and classified using the TNM system. Correlation between the number of examined lymph nodes and the staging of the tumor was examined by logistic regression analysis to establish an estimate of the minimum number of lymph nodes required to determine whether a tumor is lymph node negative. RESULTS: An average of 7.7 +/- 0.2 lymph nodes were examined per specimen in the 851 patients for whom the number of lymph nodes examined was known. The proportion of cases classified as N+ increased significantly with the number of examined lymph nodes (chi-square trend = 24.6; P < 0.0001). If the probability of correct lymph node status assessment is 1 in the reference group (comprised of pathology reports of specimens with > or = 16 examined lymph nodes), the probability of correct N+/N- dichotomization was significantly < 1 for the 1 to 3 lymph nodes group and the 4 to 7 lymph nodes group (i.e., 53.7% of cases). CONCLUSIONS: To comply with current rules for adjuvant chemotherapy, surgeons must provide pathologists with at least eight lymph nodes for optimal N+/N- dichotomization to reduce the risk of misclassification and understaging.     

Survival in patients with primary soft-tissue sarcomas treated within 6 years

Since 1988, treatment strategies for our sarcoma patients have been determined by the same team and operations performed by one surgeon. The aim of this study was to analyse prognostic data on local recurrence and survival of 101 consecutive patients who presented in our institution with the primary tumour manifestation. After a median follow-up of 35 months, the local recurrence rate was 13.5%, the mean survival time was 68 months and the 5-year survival rate was 83%. Besides positive lymph nodes (only 3 patients) the quality of resection significantly influenced local recurrences (P < 0.05). Univariate predictors of mortality were tumour grade (P < 0.01), tumour size (P < 0.05), distant metastases (P < 0.01), and resection quality (P < 0.01). Multivariate predictors of mortality consisted of grade (P < 0.0001), positive lymph nodes (P < 0.001) and resection quality (P < 0.01). In this homogeneous group of patients, excellent recurrence and survival rates could be achieved. An optimized surgical treatment not only reduces the rate of local recurrences but also augments survival time.     

Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status

BACKGROUND: Approximately 30% of the patients with primary breast cancer who have no axillary lymph node involvement (i.e., lymph node negative) at the time of surgery will relapse within 10 years; 10%-20% of the patients with distant metastases will be lymph node negative at surgery. Axillary lymph node dissection, as a surgical procedure, is associated with frequent complications. A possible alternative to nodal dissection in terms of prognosis may be the immunocytochemical detection of tumor cells in bone marrow. PURPOSE: In a prospective study, the value of tumor cell detection (TCD) in bone marrow was compared with axillary lymph node dissection in the prognosis of primary breast cancer after surgery. METHODS: Data from 727 patients with primary, operable breast cancer were included in the analysis. All patients had surgery, including axillary lymph node dissection, from May 1985 through July 1994 at the Women's Hospital of the University of Heidelberg (Federal Republic of Germany). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery while the patients were under general anesthesia. Most patients received some type of systemic adjuvant therapy. The monoclonal antibody 2E11, directed against the polymorphic epithelial mucin TAG12, was used to detect tumor cells in bone marrow samples. The association of TCD with recognized prognostic indicators was evaluated by means of chi-squared tests. Survival without the development of distant metastases (i.e., distant disease-free survival) and overall survival were estimated by use of the Kaplan-Meier method; the logrank test was used to compare survival curves. A multivariate Cox regression analysis with stratification according to adjuvant treatment type was used to assess the independent prognostic value of TCD in bone marrow in relation to other variables. Reported P values are two-sided. RESULTS: Tumor cells were detected in the bone marrow of 203 (55%) of 367 lymph node-positive patients and in 112 (31%) of 360 lymph node-negative patients. TCD was associated with larger tumors (P < .001), lymph node involvement (P = .001), and higher tumor grade (i.e., more undifferentiated) (P = .002). After a median follow-up of 36 months, patients with tumor cells in their bone marrow experienced reduced distant disease-free survival and overall survival (both P values < .001). TCD was an independent prognostic indicator for both distant disease-free survival and overall survival that was superior to axillary lymph node status, tumor stage, and tumor grade. Among patients with tumors less than 2 cm in diameter, TCD was the most powerful predictor of outcome. CONCLUSIONS AND IMPLICATIONS: TCD in the bone marrow of patients with breast cancer is a valuable prognostic tool associated with negligible morbidity. Prospective randomized studies should be performed to determine whether TCD might replace axillary lymph node dissection in a defined subgroup of patients with small tumors.     

Prognostic significance of lymph node dissection in gastric cancer

The results for 162 patients who underwent curative gastrectomy for gastric cancer from January 1988 to June 1994 were analysed statistically with special reference to the effect of lymph node dissection. Median survival was 69.3 months and the overall cumulative 5-year survival rate was 50.2 (95 per cent confidence interval (c.i.) 41.6-58.1) per cent. By univariate analysis age, histology, depth of tumour invasion, node involvement, number of metastatic lymph nodes and type of lymphadenectomy were found to be significant factors related to survival time. Multivariate analysis with the Cox model and stratified for tumour node metastasis stage revealed that only the number of metastatic nodes (P = 0.04) and the extent of lymphadenectomy (P = 0.003) affected survival independently. With respect to D1 lymphadenectomy, the relative risk associated with D2 and D4 lymphadenectomy was respectively 0.61 (95 per cent c.i. 0.34-1.10) and 0.26 (95 per cent c.i. 0.12-0.60). The 5-year survival rate was 28 per cent for patients who had a D1 dissection, 63 per cent for those who had D2 and 68 per cent for those who had D4. These results suggest that extended lymphadenectomy (D2) and especially superextended lymphadenectomy (D4) can improve survival in patients with gastric cancer.     

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.     

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.     

Lymph node dissection for T1 esophageal cancer

Proper mucosal cancer of esophagus of esophageal has no lymph node metastasis, and lymph node metastasis occurs when the tumor invades to muscularis mucosa. Submucosal cancer of esophagus has lymph node metastasis in the rate of 44.4% (40/90). The incidence and number of metastatic lymph node increase with the depth of invasion. Lymph node metastasis of esophageal cancer spreads widely to cervix, mediastinum and abdomen. It's same in submucosal cancer and first metastasis occurs also appears at everywhere from cervix to abdomen. There are high rate of lymph node metastasis in 101L, 105, 106rR, 106rL, 108, 110, 1, 2, 3, 7 lymph nodes. The cancer in upper thoracic esophagus has high rate of lymph node metastasis in cervix and upper mediastinum and lymph node metastasis of lower thoracic esophageal cancer is liable to appear in lower mediastinum and abdomen. Then the cancer in middle thoracic esophagus should be performed the lymph node dissection in cervix, mediastinum and abdomen, especially 101, 102m, 104, 105, 106r, 106t, 107, 108, 110, 1, 2, 3, 7 lymph nodes. On the other hand, cancers limited to proper mucosal layer should be treated with endoscopic mucosal resection. And its same as in the greater part of cancers invaded to muscularis mucosa and shallow layer of esophageal submucosa. The 5 year survival rate of T1 cancers of esophagus is 85.6%, which were performed surgical treatment.     

The significance of paracardiac lymph node enlargement in ovarian cancer

The computed tomography (CT) scans of 78 patients with stage II, stage III and relapsed stage I ovarian carcinoma were reviewed in order to identify the incidence of enlarged paracardiac lymph nodes in this disease, recognize their association, if any, with peritoneal metastases and establish whether they had any bearing on progression free interval and survival. Twenty-two patients (28%) were found to have enlarged paracardiac nodes, nine at initial presentation and a further 13 during the course of follow-up. The association between paracardiac node enlargement and peritoneal metastases was found to be highly significant. Thirty per cent of 27 patients with peritoneal metastases at presentation were found to have enlarged paracardiac nodes whereas of the 51 patients without peritoneal dissemination only 2% had enlarged paracardiac nodes (P < 0.001). In order to determine whether paracardiac nodal status had any independent prognostic value, multivariate analysis using Cox's regression was performed. When status at presentation was considered, the presence of enlarged paracardiac lymph nodes was found to be an independent predictor for survival. (Hazard ratio 3.70, 95% confidence interval (1.18-11.6), P < 0.04.) The hazard ratio for paracardiac nodal status with respect to progression free survival was not significant but in the expected direction. (Hazard ratio 1.85 (0.65-5.25).) When time-dependent covariate analysis was applied, paracardiac nodal status and peritoneal metastases status were found to be independent predictors for both progression free survival and overall survival. The presence of peritoneal metastases indicated a poorer prognosis than the presence of paracardiac lymph nodes, the hazards ratios for progression free survival were 12.9 and 2.58, respectively, and those for survival were 20.7 and 3.62, respectively. We have demonstrated that the presence of paracardiac lymph node enlargement is a significant adverse prognostic factor for both progression free interval and survival. The diagnosis of involved paracardiac lymph nodes is important as it can define patients having stage IV as opposed to stage III disease.     

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.     

Postoperative radiation for cervical cancer with pathologic risk factors

PURPOSE: To examine the efficacy of postoperative radiation therapy for early-stage cervical cancer with pathologic risk factors. METHODS AND MATERIALS: We reviewed the charts of 83 patients who received postoperative radiation therapy at our facility from March 1980 to November 1993 for early stage cervix cancer with positive surgical margins, positive pelvic or periaortic lymph nodes, lymphovascular space invasion, deep invasion, or for disease discovered incidently at simple hysterectomy. Twenty-eight patients received low dose rate (LDR) intracavitary radiation with or without external beam pelvic irradiation and 55 patients received external beam pelvic irradiation with high dose rate (HDR) intracavitary implants. Of these 83 patients, 66 were evaluable--20 LDR and 46 HDR patients. All patients received 45-50 Gy external beam irradiation and 20 Gy LDR equivalent intracavitary irradiation prescribed to 0.5 cm below the mucosa. Ninety percent of the LDR group and 92% of the HDR group completed treatment within < 56 days. Treatment-related toxicities were scored according to the GOG toxicity scale. Mean and median follow-up times were 101 months and 111 months (3-172 months) for the LDR group and 42 and 40 months (3-98 months) for the HDR group. RESULTS: The 5-year disease-free survival was 89% for the LDR group and 72% for the HDR group. Local control was observed in 90% (18 out of 20) of the LDR patients and 89% (41 out of 46) of the HDR patients for an overall local control rate of 89.5%. Two of 20 LDR patients (10%) experienced recurrence (two pelvic with distant metastasis). Nine of 46 HDR patients (22%) had recurrence of disease (three pelvic, four distant metastasis, and two pelvic with distant metastasis). In the HDR group, 6 out of 16 (38%) with positive lymph nodes died of disease whereas, 27 out of 30 (90%) of the patients with negative lymph nodes remain free of disease. Three of 20 (15%) LDR patients and 4 out of 46 (9%) HDR patients experienced Grade 2 or 3 late treatment- related complications. No patient in either group had Grade 4 or 5 complications. Pathologic risk factors were analyzed. Lymph node positivity and lymphovascular space invasion were found to be significant (p = 0.01 and p = 0.02). Positive margins, deep invasion, and age were not significant. CONCLUSION: Our results demonstrate the efficacy of postoperative irradiation for cervical cancer with pathologic risk factors. Overall, the local control rate was 89.5% The HDR results demonstrate that this method can be delivered safely and effectively.     

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.     

Disorders of magnesium balance

Early gastric cancer (EGC) is defined as a carcinoma limited to the mucosa or mucosa and submucosa, irrespective of whether metastasis to lymph nodes has occurred. EGC presents a much more favorable prognosis than advanced gastric carcinoma (AGC), with a 5-year survival rate between 88% and 96% for EGC versus 45% to 50% for AGC. Moreover, some gastric cancers appear as a more or less extended EGC with focal AGC (fAGC). The purpose of this study was to analyze prognostic factors in this intermediate group of tumors. From 1981 to 1992, among the 615 gastrectomy specimens with carcinoma examined at the Institute of Pathology of the University of Lausanne, only 19 tumors corresponded to the criteria of EGC with fAGC. Clinicopathologic features were studied, and a cytophotometric DNA analysis was performed. Our results show a 5-year survival rate for EGC with fAGC of 61% (11 of 18 patients alive), intermediate between that of EGC and AGC. No significant correlations were found between the most known predictive factors and prognosis. Most tumors analyzed (16 of 19) showed a diploid DNA content in the superficial as well as in the invasive areas. Contrary to the findings in the literature, which show a high-ploidy DNA pattern in most AGC, our cases show low-ploidy DNA even in the invasive portion of the tumors. In conclusion, we show that EGC with focal AGC represents a gastric cancer with an intermediate prognosis and, therefore, must be considered as a specific subtype of gastric carcinoma.