Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression

OBJECTIVES: To evaluate microstaging by means of quantifying the depth of invasion of the subepithelial connective tissue in pT1 transitional cell carcinoma (TCC) of the bladder for its additional prognostic value with respect to disease recurrence and progression. METHODS: We reviewed the pathologic findings of a consecutive series of 124 patients with pT1 tumors entered in a prospective randomized multicenter trial comparing mitomycin C and bacillus Calmette-Guérin treatment, with at least 3 years of follow-up and clinical outcome hidden from reviewers. The depth of invasion was established by identifying submucosal tumor invasion up to, in, or beyond the muscularis mucosae or vascular plexus and classified as pT1a, pT1b, or pT1c, respectively. In addition to tumor grade, the presence of carcinoma in situ (CIS) near the primary tumor or in biopsy specimens taken from abnormal looking mucosa was taken into account. The risks of recurrence and progression were calculated using Kaplan-Meier curves and modeled with proportional hazard models. RESULTS: pT1 subclassification was possible in more than 90% of the specimens. The 3-year risk of recurrence was not different in any of the subgroups. By contrast, the Kaplan-Meier 3-year risk for progression was 6%, 33%, and 55% for pT1a, pT1b (hazard ratio [HR] 5.51), and pT1c (HR 12.35) tumors, respectively (log-rank test P < 0.001). The Kaplan-Meier 3-year risk of progression was 9% versus 39% (HR 5.62) for the absence or presence of CIS in the tumor (P=0.001) and 8% versus 49% (HR 6.72) for CIS in biopsy specimens (P < 0.001). Tumor grade had no statistically significant prognostic value with respect to progression, nor had tumor volume or multifocality. The combination of the parameters (pT1c and CIS) increased the risk of progression by a factor of 27 (P < 0.0001) compared with the absence of pT1c and CIS. CONCLUSIONS: These data show that the extent of lamina propria invasion (pT1a, pT1b, pT1c) is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder. With the combination of this pT1 subclassification and the presence of CIS subgroups, distinct risks of progression can be identified that may give additional information for follow-up and treatment policies.     

Synovial sarcoma in children and adolescents: the St Jude Children's Research Hospital experience

PURPOSE AND METHODS: We reviewed the clinical records and pathologic findings of 37 children and adolescents with synovial sarcoma treated at our institution over a 30-year period to evaluate the prognostic significance of tumor size, invasiveness, histology, and other features. RESULTS: The 20 male and 17 female patients with synovial sarcoma had a median age of 13.7 years at diagnosis. Primary tumor sites were the extremities (n = 27), trunk (n = 8), and head and neck (n = 2). Disease stage (clinical group) was as follows: group I, n = 21; group II, n = 7; group III, n = 4; and group IV, n = 5. Nineteen patients had invasive (T2) lesions, 20 had tumors more than 5 cm in diameter, and 14 had histologic grade 3 lesions. The estimated 5-year survival rate (+/- SE) for patients with group I or II disease was 80% +/- 9%, compared with 17% +/- 15% for those with group III or IV tumors (P = .0003). An exact log-rank test, adjusted for clinical group, showed that tumor invasiveness and grade independently predicted overall and progression-free survival (P < .05); tumor size was significantly correlated with progression-free survival. A borderline significant relationship with overall survival was found for both tumor size and histologic subtype (P = .09). CONCLUSION: A controlled trial of adjuvant chemotherapy is merited in children with resected synovial sarcoma (clinical group I or II) who present with unfavorable clinicopathologic features such as large, invasive, or grade 3 lesions. Children with unresected or metastatic disease fare poorly despite multimodality therapy and require novel treatment approaches.     

Clinical comparison of the Alcon 20,000 Legacy and 10,000 Master phacoemulsification units

OBJECTIVES: To determine the relationship between angiogenesis and various histopathologic features as well as clinical outcome in patients with localized renal cell carcinoma (RCC). METHODS: Microvessel density was quantified by using immunocytochemical staining of endothelial cells for factor VIII-related antigen of 36 specimens taken from patients with pathologic Stage pT1 or pT2 RCC. All patients underwent radical nephrectomy and were followed for a mean time of 97.3 months. RESULTS: No association was noted between microvessel count (MVC) and either cell type, architecture, or tumor size. Inverse correlation was noted between MVC and nuclear area (P = 0.006), nuclear elipticity (P = 0.016), nuclear roughness (P = 0.039), and histologic grade (P = 0.047). Patients having tumors with low MVC had significantly better survival rate compared with those with high MVC neoplasms (P = 0.0014, by Cox proportional hazards method). CONCLUSIONS: Despite lack of correlation with known predictors of survival, MVC provides independent prognostic information for patients with localized RCC.     

Surgery versus surgery and postoperative radiotherapy in squamous cell carcinoma of the buccal mucosa: a comparative study

BACKGROUND: The efficacy of postoperative radiotherapy for squamous cell carcinoma of the buccal mucosa was evaluated. METHODS: One hundred seventy-six patients treated between 1989 and 1993 were analyzed. One hundred fifteen patients were treated with surgery alone (Group 1), and 61 patients were treated with a combination of surgery and postoperative radiotherapy (Group 2). RESULTS: Actuarial 3-year locoregional control in Groups 1 and 2 was 11% and 48% for patients with stage III + IV cancer (P = .001) and 71% and 75% for patients with stage I + II cancer (P = .74), respectively. On multivariate analysis for locoregional failure, surgical margin, bone invasion, high grade, and node involvement were significant factors in Group 1, whereas in Group 2 only tumor thickness was a significant factor. For local failure, margin, bone invasion, and stage in Group 1 and tumor thickness in Group 2 appeared as significant factors. For nodal failure, clinical nodal (cl N0 vs. N+) stage and grade in Group 1 and pathologic nodal stage (pN0 + 1 vs. pN2) in Group 2 were observed as significant factors. On subset analysis, postoperative radiotherapy was observed to have a significant advantage for surgical margins of 2 mm or less in both early pT (T1 + T2) (P = .019) and late pT (T3 + T4) (P = .016) stages. The local failure rate was higher if the time between surgery and radiotherapy was greater than 30 days. CONCLUSIONS: Postoperative radiotherapy was effective in decreasing locoregional failure in patients with close surgical margins, tumor thicker than 10 mm, high-grade tumors, positive node, and bone invasion. The effect of interval between surgery and postoperative radiotherapy on local failure was margin-dependent.     

Prognostic factors of primary transitional cell carcinoma of the upper urinary tract

OBJECTIVES: We presented and analyzed our results in order to determine the relationship between patient survival and tumor grade and/or stage. In addition, a retrospective tumor DNA ploidy study was done to evaluate its possible role in predicting future tumor recurrence in the bladder. METHODS: A total of 112 patients with upper urinary tract transitional cell carcinomas (TCCs) were recorded at our hospital. Of these, 68 patients without concurrent bladder tumors (ages ranged from 36 to 80, mean 62.4 years; male:female = 1:1.2) were treated by nephroureterectomy and bladder cuff resection. They were followed up for 14-79 months (average 38.2 months). Eight (36.4%) of the 22 patients who had stage C or D tumors had received adjuvant systemic methotrexate, vinblastine, epirubicin, cisplatin chemotherapy after surgery. DNA flow cytometry using paraffin-blocked tumor specimens was performed on the tumors of 52 patients. RESULTS: Their pathologic stages and grades were 11 at stage 0, 15 at stage A, 20 at stage B, 14 at stage C, 8 at stage D; 9 of grade I, 41 of grade II, and 18 of grade III. Postoperatively, 13 patients (19.1%) subsequently developed bladder tumors with a latent period ranging from 2 to 37 months (average 14.9 months). The difference of the tumor DNA ploidy distribution pattern among tumors of high versus low stages and/or grades is not statistically significant (p > 0.05). Overall, the 5-year survival rates for patients with low- and high-stage tumors were 100 and 66.7%, respectively; for patients with grade I-II and III tumors they were 93.6 and 28.3%, respectively. CONCLUSIONS: Patient survival was mainly related to both tumor stages (p = 0.0037) and grades (p = 0.0001), rather than to tumor DNA ploidy. For patients with grade II upper urinary tract tumors, tumor DNA ploidy seems to provide no additional predictive value on subsequent tumor recurrence in the bladder.     

Epidermal growth factor receptor expression is associated with rapid tumor cell proliferation in renal cell carcinoma

Epidermal growth factor receptor (EGF-r) expression and tumor cell proliferation rate have been proposed as potential prognostic parameters in renal cell carcinoma (RCC). In this study, immunohistochemical stains using antibodies to EGF-r and the cell proliferation marker Ki-67 (MIB-1) were used to study the relationship between EGF-r expression, tumor cell proliferation, and prognosis in 50 non-papillary RCC extending beyond the renal capsule (pT3). A high Ki-67 labeling index (LI) was associated with poor patient prognosis (P < .05). Thirty-eight cases (76%) expressed strong cell membrane immunoreactivity for EGF-r. There was a tendency toward a shortened survival for EGF-r-positive tumors (P = .08). Tumor growth fraction (Ki-67 LI) was significantly higher in EGF-r-positive tumors than in EGF-r-negative tumors (P < .05), suggesting that rapid tumor proliferation might be responsible for the poor prognosis associated with EGF-r-positive RCC.     

Angiogenesis as a predictor of long-term survival for patients with node-negative breast cancer

BACKGROUND: Angiogenesis (the formation of new blood vessels) is necessary for tumor growth and metastasis. PURPOSE: We investigated whether angiogenesis as measured by microvessel count (MVC) predicts clinical outcome in a series of patients with axillary lymph node-negative breast cancer who received no adjuvant therapy and who were followed for a long period of time. Our long-term goal is to identify those patients who may or may not need adjuvant chemotherapy. METHODS: Pathologic archival material and clinical information were analyzed for 167 patients treated with mastectomy from 1941 through 1987; none received adjuvant treatment. The median follow-up time among living patients was 15.4 years (range, 2.6-35.8 years). Ninety-six (58%) patients had a tumor size of 2 cm or less, 52 (31%) had tumors of 2.1-3 cm, and 19 (11%) had tumors of larger than 3 cm. Paraffin-embedded tissue sections were stained for expression of CD34 antigen on microvessel-associated endothelial cells by use of a monoclonal anti-CD34 antibody. Vascularity was defined as the number of microvessels (average of the three highest counts) per high-power microscopic field (400 x magnification) in the area of highest vascular density. A high vascular count was defined as 15 or more microvessels per field. Actuarial survival curves were calculated according to the Kaplan-Meier method and comparisons were made with the logrank test. The Cox proportional hazards model was used for multivariate analysis. All P values were based on two-sided testing. RESULTS: The 20-year disease-free survival (DFS) for the 167 node-negative patients treated with mastectomy and no adjuvant therapy was 74.8% (95% confidence interval [CI] = 64.7%-82.0%). The 20-year DFS was 93.1% (95% CI = 79.9%-97.7%) if the MVC was low versus 68.9% (95% CI = 56.8%-78.0%) if the MVC was high (P = .018). This difference was maintained irrespective of tumor size: for tumor size of 2 cm or less (93.3% [95% CI = 75.3%-98.3%] versus versus 67.8% [95% CI = 50.1%-80.3%]) and for tumor size of larger than 2 cm (92.3% [95% CI = 56.6%-98.9%] versus 70.9% [95% CI = 54.6%-81.6%]). However, the likelihood of a high MVC was greater with large tumors (P = .05). The proportions of tumors with low and high MVC were 33% and 67%, respectively, if the tumor size was 2 cm or less, and 20% and 80%, respectively, if tumor size was larger than 2 cm. There was no significant difference in the 20-year DFS as a function of tumor grade (P = .2). After combining patients with tumors of nuclear grades 2 and 3 compared with those of nuclear grade 1, the 20-year DFS was 93.9% (95% CI = 77.2%-98.4%) for low MVC versus 66.9% (95% CI = 52.2%-78.0%) for high MVC (P = .02). In a multivariate analysis that included the variables tumor size, age, nuclear grade, estrogen receptor status, and MVC, only MVC appeared to be an independent prognostic indicator (P = .04). CONCLUSIONS: Angiogenesis as measured by MVC is a reliable independent prognostic marker of long-term survival in patients with node-negative breast cancer. The prognostic usefulness of this marker is maintained after more than 15 years of follow-up. A low MVC identifies a subgroup of patients with DFS of 92% or more, independent of tumor size or grade.     

Lipoprotein lipase expression exclusively in liver. A mouse model for metabolism in the neonatal period and during cachexia

BACKGROUND: Most published series of ovarian carcinoma find a correlation between histologic grade and survival, but the grading system used commonly is not specified, and several different systems exist, some of which use different criteria for different histologic types. However, several studies have shown marked interobserver variability in distinguishing among the histologic types of ovarian carcinoma. The authors attempted to derive a universal grading system for all invasive ovarian carcinomas (IOC), based on the Nottingham system for grading all types of mammary carcinoma. METHODS: The authors studied 461 patients with IOC of different histologic types and clinicopathologic stages who were treated in a uniform manner between 1980 and 1994 with surgery and cisplatin-based chemotherapy. All slides were reviewed and the tumors graded as follows: Architectural pattern (predominant): Glandular = 1, Papillary = 2, and Solid = 3; Nuclear pleomorphism: Slight = 1, Moderate = 2, and Marked = 3; Mitotic activity (mitotic figures per 10 high-power fields [1 HPF = 0.345 mm2]) in most active region: 0-9 = 1, 10-24 = 2, and > or = 25 = 3; Grade 1 = total score (adding three values obtained earlier) 3-5, Grade 2 = 6 or 7, and Grade 3 = 8 or 9. RESULTS: Tumor grade correlated with survival in both early and advanced stage disease and for all major histologic types of IOC except clear cell carcinoma (CCC). Results for CCC approached but did not reach clinical significance. By multivariate analysis, only this tumor grade and performance status were significant in Stage I/II IOC. For Stage III/IV tumors, the new tumor grade also was significant, as were performance status, residual tumor size, response to chemotherapy, and mucinous (unfavorable) or transitional cell (favorable) histologic type. International Federation of Gynecology and Obstetrics grade (based primarily on architectural features) did not correlate significantly with survival except in Stage III/IV serous and Stage I/II mucinous carcinomas. CONCLUSIONS: The new grading system reported is simple, reproducible (among the current study authors), and useful for all histologic types and clinical stages of IOC. Further testing for reproducibility and clinical utility is recommended.     

Expression of nm23 in gastric carcinoma: association with tumor progression and poor prognosis

BACKGROUND: Expression of nm23 has been shown to be inversely correlated with the metastatic potential of several human cancers. In the current study, the expression and prognostic impact of nm23 was immunohistochemically studied in 413 curatively resected gastric carcinomas. METHODS: Tumor sections of the 413 gastric carcinomas were stained with a polyclonal antibody that was raised against the nm23-H1/NDP kinase A, which is identical to the nm23-H1 gene product. RESULTS: Expression of nm23 was detected in 84.5% (n = 349) of all tumors, in the majority of cases (71.2%) causing a homogeneous staining reaction in more than 75% of tumor cells. Expression of nm23 was positively correlated with the intestinal type of tumor, according to the Lauren classification and advanced pT categories, and was also correlated with the presence of blood and lymphatic vessel invasion. In contrast, no correlation could be demonstrated between nm23 expression and lymph node involvement. As shown in univariate analysis, patients with nm23 positive tumors, especially those with nm23 positive diffuse-type carcinomas, had significantly shorter overall survival than patients with nm23 negative tumors (P = 0.03 and P = 0.0065, respectively). However, in a multivariate analysis that included the prognostic parameters pT category, pN category, and blood and lymphatic vessel invasion, this prognostic impact was not maintained. CONCLUSIONS: In contrast to results for breast and colorectal carcinomas, our results for 413 gastric carcinomas showed that expression of the designated metastasis suppressor gene nm23 is correlated with aggressive tumor growth and poor prognosis but is not an independent prognostic marker.     

Mitochondrial DNA in idiopathic cardiomyopathy

143 women treated in 28 departments from 1980 to 1995 were retrospectively analysed to study the impact of prognostic factors in primary carcinoma of the fallopian tube. The mean age of the patients was 62.5 years. Sixty (42%) tumours were FIGO stage I, 28 (20%) stage II, 38 (27%) stage III, 17 (12%) stage IV. Complete radical resection was achieved in 102 (71%) patients. In 122 (85%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperative therapy consisted of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all cases was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV (P < 0.00001). FIGO stage, histological grade and presence of residual tumour had an independent prognostic impact in multivariate analysis. In order to investigate the role of p53 in primary fallopian tube carcinomas, we analysed the immunohistochemical expression of p53 protein regarding survival and FIGO stage in 63 patients (44%). No statistical significance was observed.     

Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma

PURPOSE: Thymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. We examined whether TP expression in renal cell carcinoma (RCC) is associated with microvessel density as a marker of angiogenesis, clinicopathologic characteristics, and outcome. PATIENTS AND METHODS: The enzymatic activity and expression of TP were examined in 18 RCCs and 19 kidney tissues not grossly involved with tumor from 24 patients with 13 paired samples and 11 unpaired samples by spectrophotometry and immunoblotting. The relationship between TP expression and microvessel density was assessed by immunohistochemistry in 133 RCCs. RESULTS: The median enzymatic activity of TP in RCCs was nine fold higher than that in nonneoplastic kidney tissues (P < .001). Similar results were obtained by immunoblot analysis. According to the TP staining profile, tumors were classified as no or low, intermediate, or high TP-expressing tumors. TP positivity was significantly correlated with microvessel density. TP expression was correlated with tumor grade, but there was no significant association between TP expression and other clinicopathologic characteristics. TP expression as a prognostic variable was studied using Cox's proportional hazards model. TP overexpression was an independent prognostic factor (hazards ratio, 3.95; 95% confidence interval, 0.98 to 15.89; P = .039) as were nodal category, metastases category, tumor grade, and venous invasion. CONCLUSION: These findings suggest that TP expression is correlated with microvessel density in RCC and is an unfavorable independent prognostic factor. The future development and characterization of TP inhibitors may provide a novel approach to the therapy of RCC.     

Local treatment of abdominal wound reduces tumor implantation

BACKGROUND AND OBJECTIVES: Pneumoperitoneum increases the trocar-site tumor implantation rate using a human colon cancer cell line in a hamster model. The purpose of this study was to determine whether local treatment of trocar sites with potential tumoricidal agents can inhibit tumor implantation after pneumoperitoneum. METHODS: GW-39 human colon cancer cells (0.5 ml of 2.5% v/v; 8.0 x 10(5) cells) were injected throughout the abdomen of 133 Golden Syrian hamsters through a midline incision. The animals were randomized to receive either untreated 5-mm trocars in each abdominal quadrant (group I control, n = 49), trocars dipped in 10% povidone-iodine (group II, n = 53), or trocars coated with 1% silver sulfadiazine (group III, n = 51). The midline wounds were also coated with the respective agents before closing. Pneumoperitoneum was then maintained at 10 mmHg for 10 min, after which the trocar wounds were closed. In group II, the trocar sites were treated with a coat of povidone-iodine after the trocars were withdrawn and before closing. Gross and microscopic tumor implants were analyzed at 7 weeks postoperatively. RESULTS: The rate of tumor cell implantation at trocar sites was reduced from 93% (172/184) in the control group to 75% (126/168) and 78% (141/180) in groups II and III, respectively (P < 0.0001). Fewer palpable tumors were detected in groups II and III (40% and 23%, respectively) than in the control group (72%, P < 0.0001). Mean tumor mass in group III (0.4+/-0.1 g), but not in group II (1.0+/-0.2 g), was significantly less than that in the control group (1.3+/-0.1 g, P < 0.01). Overall tumor involvement of the larger midline wound was similar for all groups (I = 80%, II = 79%, III = 71%). However, palpable tumors were identified more frequently in group I (67%) than in groups II and III (43%, P < 0.05; 22%, P < 0.01, respectively). CONCLUSION: Pretreatment of abdominal wounds with povidone-iodine or silver sulfadiazine can reduce tumor implantation after pneumoperitoneum in a hamster model.     

An endoscopic follow-up study of the development of diffuse antral vascular ectasia

AIMS: Chromogranin-A (CG), a cytoplasmic glycoprotein, is one of the markers most frequently used to identify the presence of neuroendocrine cells in the human gastrointestinal tract. Several authors have identified a subgroup of colorectal cancer patients with a sever prognosis whose tumors contained neuroendocrine CG-positive cells. In the present study, CG expression in 100 patients with colorectal adenocarcinoma treated from January 1983 to December 1988 with potentially curative surgery was analyzed and correlated with other prognostic factors and 5-year survival rate. METHODS: Samples tested immunohistochemically for CG were divided into three groups: I) negative; II) less than 1 CG-positive cell/mm2; III) more than 1 CG-positive cell/mm2. RESULTS: Of 100 patients with primary colorectal adenocarcinoma, 79% had tumors comprised of CG-negative cells, 17% had rare CG-positive cells, and 4% of cases could be classified in group III. No significant relation between CG expression and location of primary tumor, bowel wall infiltration, stage of disease or tumor grade according to Broders and Jass was observed. The 5-year survival was 53% and 52% for CG-positive and CG-negative lesions, respectively. Survival of patients with Dukes-Kirklin stage C and D was comparable in patients with CG-positive (33.3%) and CG-negative (30%) tumors. CONCLUSIONS: CG expression cannot, at present, be recommended as a marker to identify prognostic subgroups in colorectal cancer patients.     

Overexpression of epithelial macrophage colony-stimulating factor (CSF-1) and CSF-1 receptor: a poor prognostic factor in epithelial ovarian cancer, contrasted with a protective effect of stromal CSF-1

Markedly elevated levels of macrophage colony-stimulating factor (CSF-1) in the serum and ascites of epithelial ovarian cancer patients have been previously associated with a poor prognosis. However, measurements of circulating CSF-1 cannot separate CSF-1 originating in the cancer cell from that originating in stromal macrophage or fibroblast. To study the prognosis related to expression of CSF-1 and its receptor in primary and metastatic ovarian cancers and to compare the significance of epithelial versus stromal CSF-1 expression, an immunohistochemical study of 130 ovarian carcinomas was performed. Twenty-two stage I and II and 108 stage III and IV primary tumors were studied. Metastatic lesions were also studied in 96 of these 130 cases, 90 of which came from those cases with advanced-stage disease. The intensity and extent of staining for CSF-1 in epithelium and stroma and for epithelial CSF-1 receptor was scored. Kaplan-Meier curves of survival were compared with the log-rank test. The Cox regression model was used for multivariate analysis. In the primary tumors, there was strong expression of CSF-1 receptor in 65%, epithelial CSF-1 in 36%, and stromal CSF-1 in 22%. In the metastases, there was strong staining for CSF-1 receptor in 65%, epithelial CSF-1 in 41%, and stromal CSF-1 in 15%; strong staining for both CSF-1 receptor and epithelial CSF-1 was noted in 26% of the cases. When the metastases expressed both CSF-1 receptor and epithelial CSF-1 strongly, a significant decrease in disease-free survival in stage III invasive ovarian cancers was observe (P = 0.043), which was found to be an independent prognostic factor (P = 0.007), with an increased relative risk of recurrence of 2.3-fold. Although strong staining for stromal CSF-1 in the primary tumor was not found to have prognostic value, for all stages and for the subsets of stages III and IV and for stage III alone, the finding of any degree of stromal CSF-1 expression in the ovary was a favorable prognostic factor for disease-free (P = 0.046) and overall (P = 0.015) survival. This finding was associated with younger patients (P = 0.007) and low-grade tumors (P = 0.033) and was not an independent prognostic factor on multivariate analysis. Among the primary tumors, there was a significant association (P = 0.022) between stromal CSF-1 staining and lack of strong coexpression of CSF-1 receptor and epithelial CSF-1; 67 of 94 cases shared these features in the primary tumors. In the metastases of invasive stage III cases, strong staining for stromal CSF-1 was a favorable prognostic factor for overall survival in the absence of strong CSF-1 receptor staining (P = 0.033) and was associated with low-grade tumors (P = 0.0002). We report that strong expression of epithelial CSF-1 along with its receptor in the metastases of ovarian cancer patients appears to be a strong independent poor prognostic factor for outcome. We find that expression of the same cytokine (CSF-1) in the stroma of the primary tumors is associated with low-grade tumors and lack of strong coexpression of CSF-1 receptor and epithelial CSF-1, leading to an improved long-term outcome. This study may help explain the previous observations that elevated levels of CSF-1 in serum and ascites are associated with a worse prognosis in advanced ovarian cancer patients; the results suggest that the source of secreted CSF-1 may largely be the epithelium. The results of this study suggest that paracrine effects of stromal CSF-1 on tumor behavior contrast with those demonstrated when the tumor cell is capable of autocrine intracellular or extracellular interactions between CSF-1 and its receptor.     

Electrical stimulation of the trigeminal nerve root for the treatment of chronic facial pain

BACKGROUND: Alterations of the p53 gene are involved in the development of diverse human malignancies, but their incidence and clinicopathologic features are still not well characterized for endometrial carcinoma. METHODS: To investigate the clinicopathologic significance of p53, mutations and loss of heterozygosity (LOH) in endometrial carcinoma in 92 patients with this disease were examined. RESULTS: Mutations of p53 were detected in 20 (22%) of the 92 patients with carcinoma, and LOH was detected in 23 (32%) of the 72 patients in whom heterozygosity of the gene was available. There was a significant correlation between the occurrence of mutation and LOH. Mutations and LOH were more frequent in patients with Grade 3 tumors than in those with Grades 1 and 2 tumors (P = 0.0498, P = 0.0051, respectively). Patients with LOH had a poorer postoperative survival than those without LOH (P = 0.0022, log-rank test), and patients with both LOH and mutation showed the worst prognosis (P < 0.0001, log rank test). Loss of heterozygosity of the p53 gene showed a significant relation to prognosis that was independent of tumor stage, histologic grade, and muscular invasion. CONCLUSIONS: Mutation and LOH of the p53 gene are prognostic indicators in patients with endometrial carcinoma, suggesting that alterations of p53 may play an important role in the development of this cancer.     

Differential protein oxidation in Duchenne and Becker muscular dystrophy

BACKGROUND: The fifth edition of the TNM classification contains a number of changes concerning head and neck tumors. The division of Stage IV tumors into three subcategories marks a significant expansion of the stage grouping procedure. METHODS: In a retrospective study, the clinical courses of 3247 patients with carcinoma of the oral cavity, the oro- and hypopharynx, the larynx, the salivary glands, and the maxillary sinus were comparatively evaluated according to the fourth and fifth editions of the TNM classification agreed upon by the International Union Against Cancer and the American Joint Committee on Cancer. The particular aim of this study was to test the prognostic relevance of the subdivision of Stage IV, especially for mucosal carcinoma. RESULTS: In classifying the primary tumor, the most extensive changes were noted for supraglottic and salivary gland tumors. On the basis of the fourth edition of the TNM classification, the following recurrence free 5-year survival rates for 3033 cases of mucosal cancer were calculated: Stage I, 91.0%; Stage II, 78.6%; Stage III, 61.4%; Stage IV, 31.0%. The calculations based on the fifth edition yielded the following: Stage I, 91.0%; Stage II, 77.2%; Stage III, 61.2%; Stage IVA, 32.4%; Stage IVB, 25.3%; Stage IVC, 3.6%. CONCLUSIONS: The adequacy of the revised stage classification in establishing a prognostic hierarchy was confirmed. However, a significant prognostic distinction between N2 metastasis (Stage IVA) and N3 metastasis (Stage IVB) could not be found.     

Postoperative prognostic factors for carcinoma of the thoracic esophagus

To evaluate significant postoperative prognostic factors for esophageal carcinoma, clinicopathological findings and several markers for biological malignant potential were studied, including cell nuclear DNA contents, EGF receptor, p53 protein, MMP-2, Ki-67 positive cell rate, and tumors infiltrating Leu 7 cells. The subjects of this study were 96 patients with thoracic esophageal carcinoma, who underwent radical surgery with extended lymphadenectomy. In the pathological findings, the postoperative survival rate significantly correlated with depth of invasion (pT1(-2) vs. pT3, p = 0.003), lymph node involvement (pNo vs. pN1, p = 0.0002), vascular invasion (-vs. +, p = 0.0003), stage (pSt. 1-2A vs. 3, p = 0.0018), and the number of node involvements (1-3 vs. more than 4, p = 0.025). Analyzing the markers for the malignancy, a significant difference in postoperative mortality due to the relapse was recognized with p value of 0.0009 between Ki-67 positive (under 1%) and Ki-67 negative (over 1%) tumor. Ki-67 positive tumor significantly correlated with the mortality in both cases with pNo (p = 0.024) and pN1 (p = 0.020). Low-grade tumor infiltrating Leu 7 cells significantly correlated with the mortality (Grade 1+ vs. 2+, p = 0.013; Grade 1+ vs. 3+, p = 0.008). These results suggest that Ki-67 study is a useful prognostic factor after radical surgery for thoracic esophageal carcinoma.     

Orthostatic hypotension with syncope--a problem of hypertensive therapy in the aged

STUDY OBJECTIVE: To assess the efficacy of the "laryngeal lift" maneuver in improving laryngoscopic visualization to facilitate endotracheal intubation. DESIGN: Blinded study. SETTING: Operating room at Meridia Huron Hospital. PATIENTS: 305 patients receiving general anesthesia for elective surgery requiring intubation. (Five patients were eliminated from the study because we elected to intubate these patients awake and sedated.) INTERVENTIONS: Following induction of anesthesia and paralysis with muscle relaxants, laryngoscopic views of each patient were evaluated by the laryngoscopist before and after the laryngeal lift was performed by an anesthesiologist assisting the laryngoscopist. Each patient served as his or her own control group. The anesthesiologist was blinded to the results obtained by the laryngoscopist. All Grade I laryngoscopic views were eliminated (198 patients). Five patients were eliminated on the basis of obesity or atlantoaxial subluxation. The laryngeal lift was performed on the remaining 102 patients, representing Grade II to Grade V laryngoscopic views. MEASUREMENTS AND MAIN RESULTS: A modification of the original classification of laryngoscopic views by Cormack and Lehane was used: Grade I = full view of glottis; Grade II = only posterior commissure visible; Grade III = arytenoids visible; Grade IV = epiglottis visible; Grade V = no glottic structure visible. In 98 of 102 cases (96%), the maneuver improved visualization by at least 1 grade. There was no evidence of change in the 4 remaining cases. CONCLUSIONS: The laryngeal lift should be part of the anesthesiologists' armamentarium in helping the laryngoscopist who is faced with Grades II, III, IV, and V laryngoscopic views to enhance visualization of the larynx and thus facilitate endotracheal intubation.     

The histological response to chemotherapy as a predictor of the oncological outcome of operative treatment of Ewing sarcoma

Seventy-four patients who had a Ewing sarcoma of bone were managed with preoperative and postoperative chemotherapy and operative resection, with or without postoperative irradiation. The primary objectives of the study were to determine the histological response to preoperative chemotherapy in terms of the percentage of tumor necrosis and to assess the relationship between the histological response and the oncological outcome. The minimum duration of follow-up of the surviving patients who were continuously free of disease was five years. Sections of each operative specimen were examined, and the histological response to chemotherapy was graded semiquantitatively. Grade I indicated necrosis of 50 per cent of the tumor or less; grade II, necrosis of more than 50 per cent but less than 90 per cent; grade III, necrosis of 90 to 99 per cent; and grade IV, necrosis of 100 per cent of the tumor. Of the seventy-four tumors, forty-four (59 per cent) were exquisitely sensitive to chemotherapy and had complete (grade-IV) or nearly complete (grade-III) necrosis. In contrast, fourteen tumors (19 per cent) had little or no response to chemotherapy (grade I) and sixteen (22 per cent) had a moderate degree of necrosis (grade II). The histological response to preoperative chemotherapy (p = 0.0001), followed by the size of the tumor (p = 0.001), were the most important predictors of event-free survival. At five years, the rate of event-free survival was zero of fourteen patients who had had a grade-I response, six of sixteen who had had a grade-II response, and thirty-seven (84 per cent) of forty-four who had had a grade-III or IV response. The risk of local recurrence was most strongly associated with the operative margins; there were only four local recurrences (6 per cent) after sixty-seven resections with negative margins. Local recurrence may also have been influenced by the histological response and the use of local radiation. There were no local recurrences after operative treatment of six tumors that had been associated with pathological fracture. The histological response to preoperative chemotherapy and the size of the primary tumor are the most important clinical predictors of the outcome of operative treatment of non-metastatic Ewing sarcoma. These indicators should be used to identify patients who are at high risk for metastasis as such patients may be candidates for more intensive or novel therapies.     

The impact of histopathology on nodal metastases in minimal breast cancer

OBJECTIVE: To establish a model based on risk factor analysis to guide selective axillary lymph node dissection in patients with T1a and T1b breast cancers. DESIGN: Retrospective review to determine histopathologic features and patient demographic profiles that may influence the incidence of nodal metastases. SETTING: Primary care and referral centers in Rhode Island and Massachusetts. PATIENTS: Women with invasive breast cancers with nodal status reported to the statewide tumor registry, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center, Springfield, Mass, between January 1984 and December 1995. There were 12030 patients with breast cancer reported; 2185 (18%) of these had tumors 1 cm or less in diameter. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Axillary node metastases. RESULTS: The nodal status of 377 patients with T1a tumors and 1808 patients with T1b tumors was studied. Seventy-five percent had axillary dissections, and 16% were found to have nodal metastases. Thirty-one percent (29/93) of patients younger than 40 years had positive nodes compared with 15% (241/1546) of older patients (P = .001). The T1a tumors had fewer metastases than the T1b tumors did (11% vs 17%; P = .02). Nuclear grade was available in 49% of cases. Nuclear grades 2 and 3 were associated with nodal involvement twice as often as grade 1 tumors were (P = .002). Patients with no poor prognostic factors had a 7% or less chance of nodal involvement, while patients with all 3 poor prognostic indicators had a 33.5% chance of nodal involvement. CONCLUSIONS: Selective nodal dissection may be possible through risk factor analysis. Prospective registration of complete histopathologic information will allow more comprehensive analysis and may further enhance the selective treatment of patients with minimally invasive breast cancer.