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.     

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.     

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.     

Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer

PURPOSE: This prospective study was designed to evaluate the prognostic relevance and biologic characteristics of a minimal lymphatic tumor load in non-small-cell lung cancer (NSCLC). METHODS: Frozen-tissue sections from 391 regional lymph nodes of 72 patients with completely resected NSCLCs, who were staged as free of metastases (pT1-3, pN0,M0,R0) by clinical tumor staging procedures and histopathologic examinations, were studied. For tumor-cell detection, we applied the alkaline phosphatase-antialkaline phosphatase (APAAP) immunostaining technique with monoclonal antibody Ber-Ep4 against two glycoproteins of 34 and 49 kd present of the surface and cytoplasm of epithelial cells. RESULTS: Individual Ber-Ep4-positive cells were detected in 11 of 72 (15.2%) cancer patients, while positive staining was consistently absent in all sections from control nodes of 24 noncarcinoma patients. No correlation between a positive lymph node finding and either the size or differentiation grade of the primary tumor or the presence of micrometastatic tumor cells in bone marrow assessed by immunocytochemistry with antikeratin monoclonal antibody CK2 was observed. Following a median observation time of 26.0 months (range, 15 to 39), patients with lymph node micrometastases showed a significantly shorter disease-free survival duration than node-negative patients (log-rank test, P = .005). The independence of this prognostic significance was demonstrated by a multivariate analysis (Cox regression model, P = .005). CONCLUSION: Our results provide evidence that the presence of single lung carcinoma cells in lymph nodes is an independent indicator of the disseminatory capacity of an individual primary tumor. Immunohistochemical assessment of micrometastases in lymph nodes is recommended for current tumor staging in NSCLC, as it might lead to better stratification of patients for adjuvant therapy.     

Angiogenin expression and prognosis in primary breast carcinoma

Angiogenin is a protein originally isolated as an inducer of new blood vessel growth, and it has been reported to be an effective substrate for tumor cell adhesion. To understand the role of angiogenin in cancer progression, we evaluated the expression of angiogenin in 459 cases with primary breast carcinoma and in 40 benign breast specimens using an immunoassay. Higher angiogenin concentrations were observed in carcinomas in comparison with fibrocystic disease (mean, 17.3 versus 10.9 ng/mg; P = 0.008), but not with fibroadenomas. We selected 5 ng/mg cytosol protein of angiogenin as the normal cutoff for primary breast carcinoma. Eighty-eight percent of carcinomas expressed elevated angiogenin levels and 12% had low levels. We observed an association between elevated levels of angiogenin and low/ moderate histological grade (P = 0.001) and small tumor size (P = 0.026), but not with age, menopausal status, lymph node status, stage of disease, or hormonal receptor status. With a median follow-up of 31 months, breast cancer patients with elevated angiogenin levels had significantly longer disease-free survival (DFS) than patients with low angiogenin (log-rank, P = 0.003). This effect was equally observed in node-negative and node-positive cases. In a multivariate analysis of DFS, only angiogenin, tumor size, and histological grade showed statistical significance. A multivariate analysis of overall survival showed that angiogenin and tumor size were the only significant variables. Serum samples from the breast cancer patients at the time of surgery were available in 194 cases. We evaluated the levels of circulating angiogenin using the same immunoassay as in tumor tissue. Serum angiogenin levels were higher in cancer patients than in 40 healthy controls (mean, 401.2 versus 206.0 ng/ml; P < 0.0001). In breast cancer patients, we observed no correlation between the serum concentrations and the tissue levels of angiogenin (r = 0.115; P = 0.110). In addition, serum levels of angiogenin did not have a prognostic impact on the DFS of breast cancer patients (log-rank, P = 0.581). Our results indicate that elevated levels of tissue angiogenin, but not of circulating angiogenin, are a favorable prognostic factor in primary breast carcinoma, which is consistent with a role of angiogenin as a cancer cell substrate.     

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

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

Preoperative CA 15-3 concentrations predict outcome of patients with breast carcinoma

BACKGROUND: CA 15-3 is a breast-associated mucin that is elevated in the majority of breast carcinoma patients with distant metastases. Currently, the main application of this marker is in monitoring and detecting recurrences in patients with diagnosed breast carcinoma. METHODS: Preoperative serum concentrations (prior to excision of the primary tumor) of CA 15-3 were measured in 368 patients undergoing potentially curative surgical treatment for early breast carcinoma. These results were compared with prospectively recorded clinicopathologic characteristics and patient outcome data. RESULTS: A weak but significant positive association was found between CA 15-3 concentrations and both tumor stage and the number of involved axillary lymph nodes but not between CA 15-3 concentrations and estrogen receptor status. Patients with high concentrations of CA 15-3 had a significantly worse prognosis than patients with low concentrations. Using an optimum cutoff value of 30.38 U/mL, the probability of disease free survival at 5 years was 44% in patients with high CA 15-3 levels compared with 65% in patients with low CA 15-3 levels (P = 0.002, Mantel-Cox log rank test). The corresponding probabilities for overall survival were 67% and 83%, respectively (P < 0.001). The association of preoperative CA 15-3 levels with outcome was maintained in multivariate survival analysis and was not explained by the association between CA 15-3 and tumor size or lymph node burden. The relation between CA 15-3 and outcome also was found within some patient subgroups identified by traditional prognostic factors (axillary lymph node positive patients, patients with primary tumors >2 cm in greatest dimension, and patients with estrogen receptor positive tumors). CONCLUSIONS: Preoperative serum concentrations of CA 15-3 appear to have a significant relation to outcome in patients with early breast carcinoma and may have a role in the rational selection of patients for appropriate adjuvant treatments. To the authors' knowledge, CA 15-3 thus is one of the first circulating markers shown to be an independent prognostic indicator in patients with breast carcinoma.     

Prediction of occult neck metastases in laryngeal carcinoma: role of proliferating cell nuclear antigen, MIB-1, and E-cadherin immunohistochemical determination

The aim of this study is to investigate the predictive value of proliferative activity assessment and E-cadherin expression by means of immunohistochemistry in identifying patients with laryngeal squamous cell carcinoma at a high risk for occult node metastasis. Thirty consecutive patients treated for laryngeal carcinoma with false clinically negative nodes (occult metastases, pN+) between the years 1980 and 1990 were selected for this study. A group of 30 cases with negative cervical lymph nodes (pN-) having a similar anatomic site and tumor size distribution was used as control. In each case, several histological parameters, including grade, pattern of invasion, number of mitosis (x10 high-power field), tumor inflammatory infiltrate, and tumor sclerosis, were assessed. Proliferative activity was determined using immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and MIB-1. Other putative prognostic factors investigated at the immunohistochemical level were the cell adhesion molecule E-cadherin and two oncoproteins, p53 and c-erbB-2. In pN+ cases, the expression of PCNA and MIB-1 was significantly higher than in the pN- group. Moreover, a significant loss of E-cadherin expression was observed in carcinomas with occult metastases. No differences in p53 and c-erbB-2 oncoproteins were found between pN+ and pN- cases. Among the other pathological parameters examined, only histological grade was significantly associated with the presence of occult metastases, but on multivariate analysis, this relationship was lost. We conclude that PCNA, MIB-1, and E-cadherin are independent predictors of occult nodal disease in laryngeal squamous cell carcinoma, and their immunohistochemical determination could be useful in identifying patients with clinically negative lymph nodes who are at considerable risk for occult metastases and who may benefit from elective neck dissection.     

Surgical treatment in proximal bile duct cancer. A single-center experience

OBJECTIVES: The authors evaluated the experience and results of a single center in surgical treatment of proximal bile duct carcinoma. SUMMARY BACKGROUND DATA: Whenever feasible, surgery is the appropriate treatment in proximal bile duct carcinoma. To improve survival rates and with special regard to liver transplantation, the extent of surgical radicalness remains an open issue. PATIENTS AND METHODS: Retrospective analysis of 249 patients who underwent surgery for proximal bile duct carcinoma via the following procedures: resection (n = 125), liver transplantation (n = 25), and exploratory laparotomy (n = 99). Survival rates were calculated according to the Kaplan-Meier method, uni- and multivariate analysis of prognostic factors, and log rank test (p < 0.05). RESULTS: Survival rates after resection and liver transplantation are correlated with international Union Against Cancer (UICC) tumor stage (resection: overall 5-year, 27.1%; stage I and II, 41.9%; stage IV, 20.7%; liver transplantation: overall 5-year, 17.1%; stage I and II, 37.8%; stage IV, 5.8%). Significant univariate prognostic factors for survival after liver resection were lymph node involvement (N category), tumor stage, tumor-free margins, and vascular invasion; for transplantation, they were local tumor extent, N category, tumor stage, and infiltration of liver parenchyma. For resection and transplantation, a multivariate analysis showed prognostic significance of tumor stage and tumor-free margins. CONCLUSION: Resection remains the treatment of choice in proximal bile duct carcinoma. Whenever possible, decisions about resectability should be made during laparotomy. With regard to the observation of long-term survivors, liver transplantation still can be justified in selected patients with stage II carcinoma. It is unknown whether more radical procedures, such as liver transplantation combined with multivisceral resections, will lead to better outcome in advanced stages. With regard to palliation, surgical drainage of the biliary system performed as hepatojejunostomy can be recommended.     

A clinicopathologic study of mucinous gastric carcinoma including multivariate analysis

BACKGROUND: Mucinous gastric carcinoma (MGC) is a rare subtype of gastric adenocarcinoma, and its clinical and pathologic features are still controversial. To clarify the significance of this subtype of carcinoma, the authors conducted a case-control study to investigate the clinicopathologic characteristics of MGC and determine whether this mucin-producing histologic type is associated with a worse prognosis than other gastric carcinomas. METHODS: Twenty-two cases of MGC and 46 patients with nonmucinous gastric carcinoma (NGC) were included. Patients were evaluated on the basis of age, gender, tumor size, location, depth of tumor invasion, histologic differentiation, lymph node involvement, organ metastasis, stage at presentation, surgical curability, adjuvant chemotherapy and radiation therapy. To determine whether the MGC itself was an independent prognostic factor, a multivariate analysis was performed with the Cox proportional hazards model. RESULTS: The MGC patients were found to have larger tumors (P < 0.001), tumors more often located in the upper stomach (P < 0.05), more serosal invasion (P < 0.05), more lymph node involvement (P < 0.05), greater frequency of advanced stage disease (P < 0.01), and lower 5-year survival rates (P < 0.05) than NGC patients. There was no significant correlation between the subtypes of differentiation of MGC and other data, including the prognosis. Multivariate analysis showed that clinically important predictive factors were serosal invasion and disease stage at diagnosis. The mucinous histologic type itself was not an independent factor for poor prognosis. CONCLUSIONS: The overall survival rate for patients with MGC was worse than that for patients with NGC. The poor prognosis was correlated with more advanced stage at diagnosis and more frequent serosal invasion, not with the mucinous histologic type.     

Clinical significance of cyclin D1 expression in patients with node-positive breast carcinoma treated with adjuvant therapy

BACKGROUND: Experimental and clinical studies suggest that cyclin D1 is involved in transformation and tumour progression. However, there is little and contradictory data on the clinical significance of cyclin D1 in human invasive breast carcinoma. PATIENTS AND METHODS: We investigated whether the determination of cyclin D1 has prognostic value in a series of 180 patients with node-positive breast carcinoma and treated with adjuvant therapy with a median follow-up exceeding 6 years. We assessed cyclin D1 expression using the CDS-6 monoclonal antibody and a highly sensitive immunohistochemical technique. RESULTS: We found that most of the evaluable tumours (117 of 167; 70.1%) presented nuclear cyclin D1 staining and that its expression was significantly associated with both the hormone receptors (P = 0.009 and P = 0.005 for ER and PgR, respectively). Furthermore, 29 (17%) of 167 tumours had a weak (15 cases) or strong (9 cases) cytoplasmic cyclin D1 staining. In a subgroup of cases we also studied the amplification of the cyclin D1 gene and a moderate agreement between cyclin D1 nuclear overexpression assessed immunohistochemically and the gene amplification was found. In univariate analysis, cyclin D1 nuclear positivity was significantly associated with improved 6-year relapse-free survival (RFS) (P = 0.004), but not with overall survival (OS) (P = 0.12). The results of the Cox multivariate analysis (final model) indicate that cyclin D1 expression (P = 0.0049) as well as the number of involved nodes (P < 0.001) and tumour size (P = 0.036) are significant prognostic indicators for RFS. Only the number of involved nodes retained significance (P < 0.001) for OS in our series. The joint assessment of the variables considered in the final model of the multivariate analyses had a moderate prognostic capability as determined using the Harrell c statistic (c = 0.66 and 0.64 for RFS and OS, respectively). CONCLUSIONS: The patients with node-positive breast cancer who have a higher likelihood of gaining benefit from adjuvant therapy are those with tumours with cyclin D1 nuclear expression, small size and less than 3 metastatic nodes. Further studies are needed to verify the prognostic value of cyclin D1 in relation to different adjuvant treatments and to deepen the biological pathways that regulate its activation/ suppression in human breast carcinoma.     

Expression of protooncogene bcl-2 in thyroid tumors

OBJECTIVE: To determine the expression of protooncogene bcl-2 in thyroid tumors and its relationship to the development and prognosis of the tumor. METHODS: 124 cases of thyroid tissues (41 thyroid carcinomas, 53 thyroid adenomas, 20 thyroid tissues adjacent to cancer and 10 normal thyroid tissues) were immunohistochemically stained for bcl-2, by using bcl-2 protein monoclonal antibody. The positive-staining rates in different thyroid tissues were compared statistically. RESULTS: Bcl-2 immunoreactivity was found in thyroid carcinomas (43.9%), thyroid adenomas (22.6%), and thyroid tissues adjacent to cancer (15.0%). The positive-staining rate in thyroid carcinomas was higher than that in thyroid adenomas (P = 0.0439) and that in thyroid tissues adjacent to cancer (P = 0.0430). In thyroid carcinoma, the higher positive-staining rates were found in the cases of undifferentiated carcinoma and follicular carcinoma, as well as in the cases of positive lymph nodes or at tumor stage II and IV. CONCLUSION: The results suggest that the over-expression of bcl-2, a possible prognostic marker of thyroid cancer, may be related to the development of thyroid tumor.     

Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value

Cyclin D1 overexpression, detected by standard immunohistochemistry, was correlated with other prognostic variables and its prognostic value was evaluated in a group of 148 invasive breast cancers with long-term follow-up. Overexpression of cyclin D1 (59% of cases) was negatively correlated (chi 2 test) with histological grade (P = 0.0001), mean nuclear area (P = 0.004), mean nuclear volume (P = 0.02), and mitotic activity (P = 0.03) and positively correlated with estrogen receptor (P = 0.0001). There was a strong correlation between cyclin D1 overexpression and histological type (P = 0.0001). Positive cyclin D1 staining was seen in 11 of 13 tubular carcinomas, 3 of 3 mucinous carcinomas, 4 of 4 invasive cribriform carcinomas, and 17 of 20 lobular carcinomas. Of 102 ductal cancers, 52 were positive, and all 6 medullary carcinomas were negative. There were no significant correlations with lymph node status, tumor size, or DNA ploidy. In survival analysis, cyclin D1 overexpression did not provide significant univariate or multivariate prognostic value. In conclusion, cyclin D1 is mainly overexpressed in the well differentiated and lobular types of invasive breast cancer and is strongly associated with estrogen receptor positivity. It is negatively correlated with the proliferation marker mitoses count and with the differentiation markers nuclear area and nuclear volume. However, cyclin D1 overexpression does not seem to have prognostic value in invasive breast cancer when no adjuvant treatment is given.     

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.     

Primary small cell carcinoma of the esophagus: a review of the literature with emphasis on therapy and prognosis

BACKGROUND: Few studies of patients with esophageal small cell carcinoma (SCC) have been conducted. Choice of treatment remains controversial. METHODS: The authors analyzed data on 199 evaluable esophageal SCC patients, selected from among 230 patients found in the literature, and a data extraction form that recorded 11 features was completed. To allow for the evaluation of prognostic factors that influenced survival, the patients were grouped according to limited stage (LS), which was defined as disease confined to the esophagus, or extensive stage (ES), which was defined as disease that had spread beyond locoregional boundaries. Univariate and multivariate analyses were performed. Treatment was categorized as either local or local with systemic; for the ES cases, the categories were defined as treatment versus no treatment. RESULTS: The tumor site was described in 178 cases (89%). Mean tumor size was 6.1. Pure SCC was found in 137 cases (68.8%), whereas 62 cases (31.2%) showed mixed SCC; 93 (46.7%) were LS, whereas 95 (47.7%) were ES. In 11 cases (5.5%), the stage was not determined. There was a significant difference in survival between patients with LS and those with ES (P < 0.0001). The median survival was 8 months for patients with LS and 3 months for those with ES. Univariate analysis of LS showed 3 significant prognostic factors: age (for patients age < or =60 years, the median survival was 11 months, whereas for those age >60 years, the median survival was 6 months), tumor size (for those with tumors < or =5 cm, the median survival was 12 months, whereas for those with tumors >5 cm, the median survival was 4 months), and type of treatment (with local plus systemic treatment, the median survival was 20 months, whereas with local it was 5 months). In multivariate analysis, tumor size (P = 0.007) and type of treatment (P < 0.001) were shown to be independent predictive variables. CONCLUSIONS: Esophageal SCC is an aggressive type of tumor. This study shows that there are significant differences between LS and ES and that in LS, both tumor size and type of treatment are possible prognostic factors.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Prognostic value of nuclear grade of renal cell carcinoma

BACKGROUND: The authors assessed the interest and the value of Fuhrman's nuclear grade as a possible prognostic factor for renal cell carcinoma (RCC). METHODS: An 11-year retrospective study of 190 patients with RCC treated by radical nephrectomy was performed. The distribution by grade was: Grade I, 54 patients; Grade II, 58; Grade III, 58; and Grade IV, 20. The distribution of the patients by tumor stage according to the TNM15 classification was: pT1, 56 patients; pT2, 41; pT3a, 55; pT3b, 25; pT3c + pT3d + pT4b, 5; and pT4a, 8. Significant correlations with other prognostic parameters were noted. Survival curves by grade were evaluated by the Kaplan-Meier method. RESULTS: Nuclear grade was correlated with tumor stage (P = 0.0001), synchronous metastases (P = 0.003), lymph node involvement (P = 0.0001), renal vein involvement (P = 0.0001), tumor size (P = 0.0001), and perirenal fat involvement (P = 0.001). No correlation was found between nuclear grade and tumor multicentricity (P = 0.14) and cell type (P = 0.2). Nuclear grade was an effective parameter in predicting development of distant metastases after nephrectomy. Among the 54 patients who presented with Grade I tumors, only one tumor did metastasize during the 5-year follow-up, whereas 17% of the Grade III and 30% of the Grade IV tumors metastasized. The 5-year actuarial survival rates of the patients with Grade I, II, III, and IV tumors was 76%, 72%, 51%, and 35%, respectively. The comparison of the survival curves by grade showed a statistically significant difference between the curves when Grade I and II tumors were compared with Grade III and IV tumors (P = 0.001). CONCLUSION: In this study, nuclear grade was found to have prognostic significance and seems to be an important criterion when considering the outcome of patients with RCC.     

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

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

High-dose rate intracavitary irradiation for carcinoma of the uterine cervix. The adverse effect of treatment prolongation

AIM: To investigate the adverse effect of treatment prolongation on the local control and survival of the cervical carcinoma of the uterus. PATIENTS AND METHOD: Two hundred and sixteen patients with stage IIB and III cervical carcinoma treated with a combination of external radiation and high-dose rate (HDR) intracavitary irradiation between 1978 and 1989 were retrospectively studied. A multivariate analysis was used to determine the effect of treatment time on local control and survival. RESULTS: Overall treatment time was the most highly significant factors for local control in the multivariate analysis (p = 0.0005). The 5-year cumulative relapse rates were significantly different with the treatment times 35 to 42 days: 9% versus 43 to 49 days: 19% versus 50 to 62 days: 42% (p = 0.001). The second most significant parameter was stage classification (p = 0.02). Concerning relapse-free survival, stage classification (p = 0.0001), overall treatment time (p = 0.0035) and hemoglobin level (p = 0.0174) were the 3 most important prognostic factors, although there was no relationship between treatment time and late complications. CONCLUSION: These results suggest that prolongation of treatment time is associated with decreased local control and survival in patients treated with external radiation and HDR intracavitary irradiation.     

Lymphatogenous spread of renal cell carcinoma: an autopsy study

PURPOSE: We investigated the occurrence and extent of metastatic spread, especially regarding lymph nodes, of renal cell carcinoma. MATERIALS AND METHODS: From 1958 to 1982, 554 cases of renal cell carcinoma were diagnosed at autopsy. Clinical data and autopsy findings were reevaluated, and the occurrence of lymph node metastases was analyzed by histological examination of retroperitoneal, mediastinal, supraclavicular, axillary and inguinal lymph nodes. RESULTS: Distant metastases were revealed in 119 cases (21.5%), including 31 (5.6%) with single metastases. In 88 cases (16%) renal cancer was the cause of death. Lymphatogenous dissemination was detected in 80 cases of which 75 had additional, mostly multifocal metastatic spread. Consequently lymph node metastases restricted to the paracaval and/or para-aortic lymph nodes were noted in only 5 cases (0.9%). CONCLUSIONS: Of the 554 cases of clinically unrecognized renal cell carcinoma almost all with lymphatic spread had additional distant metastases. Therefore, the therapeutic effect of extensive retroperitoneal lymph node dissection in association with radical nephrectomy seems to be low. However, more limited lymph node dissection may be useful, mainly as a staging procedure.