Cumulative Disease-free Survival Research Articles

High Expression of CD105 as a Prognostic Predictor of Early Tongue Cancer

The purpose of this article is to investigate the expressions of vascular endothelial growth factor (VEGF) and endoglin (CD105) in the biopsy tissues of squamous cell carcinoma of the tongue in early tumor stages and their relationship with the clinicopathologic features. The authors conducted retrospective clinical and biologic studies. Immunohistochemistry was used to study the expressions of VEGF and CD105 in the biopsy tissues taken from 94 patients with T1 and T2 tongue cancers. The expressions of VEGF and CD105 were analyzed and correlated to the clinicopathologic features of these patients. High expressions of VEGF and CD105 significantly correlated with a relatively advanced tumor stage (P=.001 and P<.001), positive nodal status (P<.001 and P<.001), presence of tumor necrosis (P=.022 and P=.01), and greater tumor thickness (P<.001 and P<.001), respectively. In addition, high expression of CD105 correlated with the presence of perineural invasion (P=.003). However, the expression of VEGF and CD105 did not significantly correlate with age, gender, vascular invasion, or histologic grading. The cumulative 5-year disease-free survival rate significantly correlated with low expression of VEGF (P=.003), CD105 (P<.001), positive nodal status (P<.001), a relatively advanced tumor stage (P=.024), greater tumor thickness (P=.023), and presence of tumor necrosis (P=.003). Nonetheless, Cox's regression analysis revealed that only the expression of CD105 was an independent prognostic predictor for survival (P<.001). Higher expression of either CD105 or VEGF in the tumor bed implicates a more aggressive potential for T1 and T2 tongue cancers, and the expression of CD105 is a useful predictive prognostic factor in early tongue cancer.

Concurrent chemoradiation (CCR) for locally advanced or relapsed vulvar carcinoma (VC) treatment: An alternative to pelvic exenteration (PE)

15021 Background: PE is the standard treatment for locally advanced or relapsed VC that involves the anus or rectovaginal wall, with high morbidity and the consequent loss of Qol. Objective: Locoregional response, toxicity, disease free survival (DFS) and survival (SV) achieved with concurrent chemoradiation in locally advanced or relapsed VC was prospectively evaluated. Methods: From 7/93 to 05/05, 32 pts which would have required some kind of PE were treated with mitomycin C (10 mg./m2 d1) + 5-Fluoruracil (800 mg/m2 d 1–4) IV continuous infusion, plus concurrent external radiotherapy (50 Gy) to the vulva, pelvis and groin. An additional boost (15–20 Gy) was added when a less than complete clinical response (CR) was achieved. Multiple biopsies of the tumor bed were performed to confirm complete pathologic responses (CPR). Results: 30 pts (94%) completed treatment as planned. Overall, locoregional response was obtained in 25/30 (83.3%) pts: 20 (66.6%) CR, 5 (16.6%) partial response (PR). 3 (10%) pts had stable disease and 2 (6.6%) progresive disease. 14/30 (46.6%) had CPR. Radical vulvectomy or radical local excision was performed in 7 pts for residual disease after CCR (4/6 with CR and microscopic residual disease and 3/5 with PR), 2 pts with PR were lost after having completed CCR and 2 pts with CR and microscopic residual disease refused further treatment. None of the responding patients required PE. Treatment was well tolerated with mild to moderate toxicity, attributed to radiotherapy. No treatment deaths were recorded. 28 pts with a median follow-up of 25.5 months (range 6–126) showed a 5-year cumulative DFS (34%) and SV (49%). Conclusion: CCR is a safe therapeutic option with results comparable to those obtained with PE, with significant improvement of Qol. CCR has become the standard treatment for locally advanced or relapsed VC at our center. No significant financial relationships to disclose.

Intrahepatic recurrence after percutaneous radiofrequency ablation of hepatocellular carcinoma: Analysis of the pattern and risk factors

Purpose To evaluate the pattern and risks for intrahepatic recurrence after percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC). Materials and methods We studied 62 patients with 72 HCCs (≤4 cm) who were treated with percutaneous RF ablation. The mean follow-up period was 19.1 months (6.0–49.1). We assessed the incidence and cumulative disease-free survival of local tumor progression (LTP) and intrahepatic distant recurrence (IDR). To analyze the risk factors, we examined the following, for the LTP: (1) tumor diameter, (2) contact with vessels, (3) degree of approximation to hepatic hilum, (4) contact with hepatic capsule, (5) presence of ablative safety margin, (6) degree of benign periablational enhancement and (7) serum alpha-fetoprotein; for the IDR: (1) severity of hepatic disease, (2) presence of HBsAg, (3) serum alpha-fetoprotein, (4) whether RF ablation was the initial treatment and (5) multiplicity of tumor for IDR. Results The incidence of overall recurrence, LTP and IDR was 62.9%, 26.4% and 53.2%, respectively. The cumulative disease-free survival rates were 52%, 82% and 56% at 1 year, 26%, 63% and 30% at 2 years, respectively. Univariate analysis showed that the significant risk factors for LTP were: a tumor with a diameter >3 cm, contact of HCC with a vessel and an insufficient safety margin ( p < 0.05). A multivariate stepwise Cox hazard model showed that the measurement of a tumor diameter >3 cm and insufficient safety margin were independent factors. Only the increased serum alpha-fetoprotein was a significant risk factor for IDR ( p < 0.05). Conclusion Intrahepatic recurrence after percutaneous RF ablation is common. Large HCC (>3 cm) with high serum alpha-fetoprotein should be treated more aggressively because of higher risk for recurrence.

Galectin-9 as a Prognostic Factor with Antimetastatic Potential in Breast Cancer

Galectin-9, a member of the beta-galactoside-binding galectin family, induces aggregation of certain cell types. We assessed the contribution of galectin-9 to the aggregation of breast cancer cells as well as the relation between galectin-9 expression in tumor tissue and distant metastasis in patients with breast cancer. Subclones of MCF-7 breast cancer cells with high or low levels of galectin-9 expression were established and either cultured on plastic dishes or transplanted into nude mice. The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry. The patients were followed up for 14 years. MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in culture and in nude mice. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins. Tumors of 42 of the 84 patients were galectin-9 positive, and those of 19 of the 21 patients with distant metastasis were galectin-9 negative. None of the 13 patients with galectin-9-positive tumors and lymph node metastasis up to level II manifested distant metastasis. The cumulative disease-free survival ratio for galectin-9-positive patients was more favorable than that for the galectin-9-negative group (P < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independently of and to a greater extent than lymph node metastasis. Galectin-9 is a possible prognostic factor with antimetastatic potential in breast cancer.

Aberrant promoter hypermethylation of multiple genes in head and neck squamous cell carcinoma

Purpose Epigenetic alteration, via promoter hypermethylation, inactivates genes important for the development of head and neck squamous cell carcinoma (SCCHN). The aim of this study is to characterize and correlate, with clinical parameters, the promoter methylation profile of DNA repair genes, hMLH1 and O6-methylguanine-DNA methyltransferase (MGMT), and tumor-suppressor gene p16. Materials and methods Fifty-one cases of SCCHN, collected from the paraffin block archives (1997–1999) in the Department of Pathology at the University of Arkansas for medical sciences, provided DNA for methylation-specific PCR using primers specific for hMLH1, MGMT, and p16. Results Sixty-two percent displayed promoter hypermethylation in at least one gene, with 23% seen for hMLH1, 30% for MGMT, and 36% for p16. Promoter hypermethylation of these genes separately or in combination was not associated with history of smoking and alcohol use, tumor size, nodal status, clinical stage, and overall survival. Promoter hypermethylation of more than 1 gene was significantly associated with increased 2-year disease-free survival. The probability of surviving 2 years without tumor recurrence was 100% with promoter hypermethylation in 2 or 3 genes and 46% with promoter hypermethylation in none or just 1 gene ( P = .013). Promoter hypermethylation of 2 or 3 genes was independently related to increased 2-year cumulative disease-free survival ( P = .028). Conclusions Promoter hypermethylation of hMLH1, MGMT, and p16 genes was commonly detected in 47 SCCHN cases with up to 65% showing aberrant promoter hypermethylation in at least 1 gene. Promoter hypermethylation of 2 or 3 genes was significantly associated with increased 2-year disease-free survival, suggesting that promoter hypermethylation of multiple genes might improve survival. Significant correlation was also noted between a positive alcohol use history and promoter hypermethylation of the MGMT gene with no promoter hypermethylation of the p16 gene.

Limited Surgery and Tamoxifen in the Treatment of Elderly Breast Cancer Patients

A conservative approach to treating breast cancer patients was adopted for those more than 70 years of age with T1-3 and small localized T4b N0-1 lesions. It consists of tumor excision or simple mastectomy with adjuvant tamoxifen. From the prospective breast cancer database, patients 70 years or older at the time of diagnosis were identified for the period January 1990 to December 1996. Demographic, clinical, pathological, and oncologic data were retrieved. A total of 236 patients were identified. Ninety-seven patients (41%) were treated according to the conservative protocol. Of these, 74 had a tumor excision and 23 had a simple mastectomy. Their mean age was 79 years. TNM staging was stage I in 18 patients, stage II in 66 patients, and stage III in 13 patients. There was no 30-day mortality. Eleven patients were not compliant with tamoxifen use. Two patients were lost to follow-up. The mean follow-up is 51 months (range 4 to 109 months). The cumulative incidence of local and regional recurrence at 8 years is 5% and 7%, respectively. Locoregional recurrences were controlled with excision, mastectomy, or axillary dissection. The cumulative disease-specific, overall, and disease-free survival at 5 years is 86%, 64% and 46%, respectively. Tumor excision or simple mastectomy with tamoxifen offers sufficient tumor control for elderly patients. Axillary dissection and breast or chest wall radiotherapy can safely be omitted, thereby greatly reducing health care resource utilization.

Myeloid antigen expression provides favorable outcome in patients with adult acute lymphoblastic leukemia: a single-center study.

Between July 1992 and July 2001, 81 patients with de novo adult acute lymphoblastic leukemia (ALL) treated according to the German Multicenter Study Group for Adult ALL (GMALL) 01/81 protocol were evaluated in order to analyze the effect of aberrant myeloid antigen expression on prognosis. We observed myeloid antigen aberrant expression in 21 of the adult ALL cases. We did not observe any effect of aberrant myeloid antigen expression on the time to achieve remission, relapse rate, and death rate. After 5 years of follow-up, cumulative disease-free survival of myeloid antigen (My) (+) and My (-) adult ALL patients was 67% and 43%, respectively. These data were not found to be statistically significant (P=0.29), but we did find a statistically significant difference in overall survivals between these two groups (85% vs 50%) (P=0.05). Twenty-nine patients died and the remaining 52 patients were followed for a median of 31 months. We could not find any special effect of the known prognostic factors on prediction of relapse in multivariate analysis. However, myeloid antigen expression was the most significant factor, which affected long-term survival in our patients (P=0.01). These data indicate that myeloid antigen expression is useful for predicting a favorable outcome of adult patients with ALL.

Diagnosis and patient management of intraductal papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography

Background & Aims:Intraductal papillary-mucinous tumor (IPMT) of the pancreas has attracted increasing interest because of its unique presentation. The differential diagnosis between malignant and benign tumors is extremely important in the determination of the therapy for IPMT. The aims of this study are to determine the usefulness of peroral pancreatoscopy (POPS) and intraductal ultrasonography (IDUS) in IPMT for the differentiation of malignant from benign disease, and to evaluate the significance of these techniques as new preoperative examinations. Methods:Sixty histopathologically confirmed patients with IPMT underwent POPS and/or IDUS preoperatively. POPS was perfomed in all patients, and IDUS in 40. Findings of POPS and IDUS were compared with histopathology of resected specimens. The postoperative follow-up data were analyzed. Results:Protruding lesions were detected by POPS in 40 patients. They were classified into 5 groups. Fish-egg-like type with vascular images, villous type, and vegetative type were considered to be malignant. By IDUS, lesions protruding 1 mm or more were observed in 36 patients. Of the lesions protruding 4 mm or more, 88% were malignant. Combination of POPS and IDUS improved the differential diagnosis between benign and malignant IPMT. The 3-year cumulative survival rate and disease-free survival rate were extremely high at 95% and 93%, respectively. Conclusions:The combination of POPS and IDUS results in a considerably improved differential diagnosis between malignant and benign IPMT and is useful for determining an effective therapeutic approach. These new techniques can contribute to improvements in postoperative results.

Polymorphisms in the coding region of mtDNA and effects on clinical outcome of unrelated bone marrow transplantation.

The entire protein-coding region was divided into 45 fragments, separately amplified and analyzed for polymorphism by the PCR-SSCP (single-strand conformation polymorphism) method. The effect of polymorphism mismatching on the clinical outcome of unrelated bone marrow transplantation was studied to clarify whether products from mtDNA become minor antigens. Variability in PCR-SSCP pattern combinations of the 45 fragments suggests that each individual has a different polymorphism combination in the protein-coding region if all the coding regions were compared at the nucleotide sequence level. Nonsynonymous polymorphisms were found at relatively high frequency in MTATP8 and MTND3. Both the polymorphisms with and without substitution matched the peptide-binding motifs of HLA-A*0201. The effects of the polymorphism matching were retrospectively analyzed in 340 recipients transplanted with HLA-A, -B, -DRB1 allele-matched bone marrow from unrelated donors. There were no effects of polymorphism matching on the incidence of acute GVHD and cumulative disease-free survival. These results suggest that polymorphisms which generate peptides, with and without substitutions, that bind the same HLA molecule hardly influence GVHD because the difference between the HLA-peptide complexes is minute.

High preoperative serum carcinoembryonic antigen predicts metastatic recurrence in potentially curative colonic cancer: results of a five-year study.

Serum carcinoembryonic antigen is used mainly for tumor follow-up to detect recurrence of colonic cancer. However, raised preoperative carcinoembryonic antigen levels may be helpful for the identification of understaged cases and of patients meriting more intensive preoperative and postoperative diagnostic workup. From a prospectively collected database, the data on 261 patients who had curative colonic carcinoma with a minimal follow-up of five years and who had preoperative carcinoembryonic antigen levels assessed were retrieved and analyzed. Outcome parameters were local and/or distant recurrence and time to recurrence. These parameters were correlated with Dukes staging and preoperative carcinoembryonic antigen levels. The cumulative disease-free survival of patients with a preoperative carcinoembryonic antigen level within the normal range was significantly better than that of those whose carcinoembryonic antigen was 5 ng/ml or more (P = 0.001). No patient with carcinoembryonic antigen levels less than 1 ng/ml developed metastatic recurrence. Twenty-three percent of all patients with a raised carcinoembryonic antigen above 5 ng/ml compared with 2.1 percent of patients with carcinoembryonic antigen below 5 ng/ml developed a metastasis at two years. At five years, these figures were 37.2 percent and 7.5 percent, respectively. Dukes staging and carcinoembryonic antigen levels were found to be directly correlated (P < 0.001) when all patients were included. Carcinoembryonic antigen of more of 15 ng/ml was found to be a significant adverse prognostic indicator for disease-free survival irrespective of Dukes staging (P < 0.02). Raised carcinoembryonic antigen levels predicted distant metastatic recurrence (P < 0.001) but did not predict local recurrence (P = 0.72). High preoperative carcinoembryonic antigen levels above 15 ng/ml predicted an increased risk of metastatic recurrence in potentially curative colonic cancer and may indicate undetectable disseminated disease. Preoperative carcinoembryonic antigen levels predict understaging and the possibility of distant recurrence. Such patients may therefore be selected for adjuvant therapy where indicated. Therefore, carcinoembryonic antigen is complementary to conventional Dukes staging for the prediction of recurrence and survival.

The role of preoperative brachytherapy as an adjunct to surgery and postoperative radiotherapy in the treatment of stage I endometrial carcinoma

Purpose: Between 1978 and 1993, 817 cases of endometrial carcinoma were treated with simple hysterectomy with bilateral salpingo-oophorectomy. Five hundred and twenty-six cases had preoperative brachytherapy (Preo), and 291 cases underwent surgery without preoperative radiotherapy (Nopre). The aim of the study was to compare disease-free survival of the two groups. Methods and materials: Survival comparison of the two groups was controlled for postoperative treatment type, according to stage, histological type, degree of differentiation, depth of myometrial invasion and age. The life-table method was used for survival analysis. Cumulative disease-free survival probabilities were calculated as a function of the proportion of normal remaining life elapsed from the time of diagnosis. Results: Five-year disease-free survival of patients with and without preoperative brachytherapy in stage IA, IB and IC was 93 and 93.6%, 93 and 94%, and 80 and 65%, respectively. In well differentiated tumors and poorly differentiated tumors, there was no difference in disease-free survival between patients with and without preoperative brachytherapy. Patients with moderately differentiated tumor treated with preoperative brachytherapy had significantly better disease-free survival than those without preoperative radiotherapy, however, this was confounded by uneven distribution of invasion depth. Conclusion: Preoperative brachytherapy plays a limited role in the treatment of early stage endometrial carcinoma.

Effect of oral adjuvant therapy with Carmofur (HCFU) for distant metastasis of colorectal cancer

Background. The effectiveness of adjuvant chemotherapy for colorectal cancers after curative resection has been reported recently; this study was performed to clarify the reasons of for this effectiveness, which have been unclear. Methods. Two joint prospective clinical randomized studies were performed. In the first study, of patients operated on between July 1, 1981 and June 30, 1983, at 41 Centers in the Tokai district, 172 patients with colorectal cancer were allocated to two groups. In the control group, mitomycin C (MMC) was given eight times intravenously in the 4 weeks after surgery. The other group, in addition to receiving the same regimen as the controls, received oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) at 600 mg/day for at least 6 months after the 4-week MMC treatment. In the second study of patients operated at 7 Centers in the Tokai district between October 1, 1987 and September 30, 1990, 173 patients with colorectal cancer were allocated to two groups after surgery, a control group receiving no HCFU, the other group receiving HCFU at 0.8 mg/kg per day orally, for 1 year, beginning 4 weeks after the operation. Results. In the first study, the cumulative 10-year survival rate of the MMC + HCFU group was higher than that of the MMC-alone group (P < 0.05). In the second study, the cumulative 5-year disease-free survival rate of the HCFU group was higher than that of the control group (surgery alone; P < 0.05). In patients with colon cancers, the rate of distant metastases for all evaluable patients was lower in the MMC + HCFU group than in the MMC-alone group in the first study (P < 0.05), and the rate was lower in the HCFU group than in the surgery-alone group in the second study (P < 0.02). Conclusion. The effectiveness of HCFU in reducing the disease-free survival rate appeared to be mainly due to its preventive effect on distant metastases.

Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma.

This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma. A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked immunoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. The results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regression analysis. The stability of the predictive value of both markers was assessed: 1) by splitting the follow-up into three intervals and performing separate analyses for each period and 2) graphically by plotting the corresponding cumulative hazards ratio along the follow-up. Eighty-two (47%) tumors manifested overexpression of p53 protein and 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaining and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and proved to have independent prognostic significance. Analysis performed in different time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years after surgery (hazards ratio, 3.26; 95% confidence interval 95% CI, 1.65-6.42). The presence of p53 immunoreactivity in the primary tumor was an indicator of a high risk of recurrence only after the first year of follow-up (hazards ratio, 4.02; 95% CI, 1.68-9.6). The serum CEA level and expression of p53 protein provide complementary prognostic information. Time-dependency of the prognostic influence of both parameters should be taken into consideration when establishing postoperative predictive estimations.

Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma

BACKGROUND This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma. METHODS A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked immunoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. The results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regression analysis. The stability of the predictive value of both markers was assessed: 1) by splitting the follow-up into three intervals and performing separate analyses for each period and 2) graphically by plotting the corresponding cumulative hazards ratio along the follow-up. RESULTS Eighty-two (47%) tumors manifested overexpression of p53 protein and 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaing and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and proved to have independent prognostic significance. Analysis performed in different time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years after surgery (hazards ratio, 3.26; 95% confidence interval [95% CI], 1.65–6.42). The presence of p53 immunoreactivity in the primary tumor was an indicator of a high risk of recurrence only after the first year of follow-up (hazards ratio, 4.02; 95% CI, 1.68–9.6). CONCLUSIONS The serum CEA level and expression of p53 protein provide complementary prognostic information. Time-dependency of the prognostic influence of both parameters should be taken into consideration when establishing postoperative predictive estimations. Cancer 2000;88:35–41. © 2000 American Cancer Society.

Surgery for gastric remnant carcinoma following Billroth II gastrectomy

Between January 1983 and December 1995, 31 patients with gastric remnant carcinoma were operated on 6-45 years after a Billroth II resection for peptic ulcer disease. Total gastrectomy with Roux-en-Y reconstruction was performed in all cases. In 16 patients (52%) extended resection with removal of one or more adjacent organs was necessary for oncological reasons. In this elderly population with a high incidence of pre-operative risk factors (55%), most tumours were classified as stage III or IV (45%). Although total gastrectomy should be the surgical option of first choice for gastric remnant carcinoma, it resulted in high levels of post-operative mortality and morbidity (13% and 35%, respectively), especially in patients with stage III and IV tumours who underwent resection of an adjacent organ. Despite extended surgery, if necessary, the recurrence rate after 'curative' surgery is high (8/20 patients) and the cumulative disease-free 5-year survival rate was 48%. Detection of the tumour at an earlier stage not only limits the extent of resection and lowers the complication rate, but also improves survival.

Isolated Vaginal Recurrences in Endometrial Carcinoma: Treatment Results Using High-Dose-Rate Intracavitary Brachytherapy and External Beam Radiotherapy

Purpose.To evaluate the long-term disease control, survival and complication rates using high-dose-rate intracavitary brachytherapy (HDRB) and external beam radiotherapy (EBRT) for patients found to have isolated vaginal recurrences from early-stage endometrial adenocarcinoma following total abdominal hysterectomy and bisalpingo-oophorectomy (TAH BSO).Materials and Methods.Twenty patients originally diagnosed with early-stage endometrial adenocarcinoma (FIGO stage I or II) following TAH BSO developed isolated vaginal recurrences and were referred to our radiation oncology department for definitive treatment. The median time between TAH BSO and vaginal recurrence was 24 months. Thirteen patients received combined modality treatment (EBRT + HDRB) and seven patients received HDRB only. Median prescribed dose was 4400 cGy by EBRT and 2400 cGy to the vagina mucosa surface by HDRB in the combined modality group. Median prescribed dose was 3500 cGy to the vagina mucosa surface for the HDRB only group. These patients were followed for a median duration of 47.5 months following treatment for isolated vaginal recurrence.Results.Eighteen of 20 patients (90%) achieved a complete response to therapy and the remaining 2 achieved a partial response. Four of 18 complete responders developed a second recurrence within 30 months following radiotherapy. Ten-year cumulative local control rate was 74%. Ten-year cumulative cause specific and disease-free survival rate was 71 and 46%. Overall late complication rate was 15%; there were no grade 3 or 4 late complications. Three patients developed grade 2 late complications from treatment; all 3 were from the combined modality group (HDRB + EBRT).Conclusion.The use of HDRB resulted in high complete response rates and durable long-term disease-specific survival in a substantial percentage of patients. To our knowledge, this study represents the first published results on treatment of vaginal recurrences with HDRB. Although the number of patients in this study is small, treatment results compare favorably to those obtained from patients treated with low-dose-rate brachytherapy ± EBRT from other studies.

Epidermal Growth Factor Receptor in Vulvar Malignancies and Its Relationship to Metastasis and Patient Survival

Objective.To evaluate the level of epidermal growth factor receptor (EGF-R) expression in vulvar malignancies and to determine if a correlation exists between EGF-R levels and metastasis or patient survival.Methods.All patients with a diagnosis of invasive squamous cell carcinoma of the vulva who were treated at our institution with a primary radical vulvectomy and inguinal lymph node dissection from 1983 to 1993 were eligible for the study. Sixty-one patients with available tissue blocks of benign vulvar epithelium, the primary malignant vulvar lesion, and groin node metastasis (when positive) were included in the study. Semiquantitative EGF-R expression was determined in a blinded fashion utilizing immunohistochemical staining of appropriate tissue samples. Survival was calculated utilizing Kaplan–Meier life table analysis based upon disease-free survival.Results.A significant increase (P< 0.001) in mean EGF-R levels was demonstrated in the primary tumor (67%) versus benign vulvar epithelium (31%). In the 14 patients with lymph node metastasis, the mean EGF-R level in the primary tumor was 65% versus 88% in the metastatic lesion (P< 0.001). The likelihood of lymph node metastasis was elevated in those patients with a benign tissue EGF-R level ≥40% (P< 0.03) and in those patients with a primary tumor EGF-R level ≥90% (P< 0.025). Life table analysis revealed a cumulative disease-free survival of 45% for all patients. Disease-free survival in those patients with EGF-R levels ≥90% in the primary tumor was 25%, contrasting with a disease-free survival of 54% in those patients with EGF-R levels <90% (P< 0.05).Conclusions.There is a progressive increase in EGF-R expression from benign vulvar epithelium to primary malignant tissue to metastatic lesions within the same patient. Increased expression of EGF-R in the primary vulvar malignancy is significantly associated with lymph node metastasis and decreased patient survival. Increased expression of EGF-R in histologically benign vulvar epithelium has a significant association with lymph node metastasis and may predict decreased patient survival.

Asymptomatic colorectal cancer detected by screening.

Colorectal cancer screening has become prevalent. To discuss the efficacy of screening, we studied the characteristic of asymptomatic colorectal cancer detected by screening. This is a retrospective review of patients with colorectal cancer treated at our institution. During the past 20 years, 96 of 1,046 cases of colorectal cancer were asymptomatic and detected by screening. Sixty-one of these cases were detected in the recent five years. The initial screening procedures were fecal occult blood test in 51 cases, sigmoidoscopy or colonoscopy in 18, barium enema in 9, and other tests in 18. Thirteen lesions (14 percent) were smaller than 1.0 cm and 32 (33 percent) were 1-2 cm in size. There were 34 Tis, 21 T1, and 8 T2 tumors. Of the 55 Tis or T1 lesions, 14 showed nonpolypoid growth (5 flat-elevated, 7 flat-elevated with depression, 1 flat, 1 depressed), and 12 of these were detected on endoscopy. Thirty-four cases were TNM Stage 0, 25 were Stage I, 16 were Stage II, 12 were Stage III, and 9 were Stage IV. Sixty-one percent of those detected by screening were in either Stage 0 or Stage I compared with 16 percent in the symptomatic group. Cumulative five-year disease-free survival rates were 100 percent for both Stage 0 and Stage I, 94 percent for Stage II, and 52 percent for Stage III. Overall cumulative five-year survival rate was 87 percent for those detected by screening, compared with 57 percent in symptomatic patients. Asymptomatic cancers detected by screening were at a less advanced stage. In particular, many nonpolypoid early cancers were detected by endoscopic screening.

HLA class I antigens are possible prognostic factors in hepatocellular carcinoma

Thirty patients who underwent hepatectomy for the treatment of hepatocellular carcinoma (HCC) were examined for expression of HLA class I antigens on HCC cells by flow cytometry. The expression was found significantly lower in cases of stage IV compared with those of stage I or stage II (p<0.05), and in cases of intrahepatic metastases compared with those without metastases (p<0.001). In cases of non-curative hepatectomy, the expression of HLA class I antigens was lower compared with those treated by curative resection. Postoperative cumulative disease-free survival rates were well correlated with the expression rate of HLA class I antigens (p<0.05). Expression of HLA class I antigens on HCC may indicate low malignancy and better prognosis.

Postoperative Stay Associated with Prognosis of Patients with Colorectal Cancer

The author's objective was to determine whether the length of postoperative stay for patients after colorectal cancer surgery is associated with prognosis. Financial pressure to reduce hospital costs has caused physicians to reduce hospital stays by changes in patient care, which reduce hospital stay but may compromise long-term results. Using multivariate analysis, the author examined the relationship between postoperative stay and prognosis in a consecutive series of 341 prospectively studied patients with colorectal cancer undergoing potentially curative surgery. In multivariate analysis, patients staying beyond the median of 11 days had more complications (p=0.000), more left hemicolectomies and procedures with colostomies (p=0.000), were older (p=0.002), and lost more blood (p=0.012) than patients staying less than the median. Disease-free survival was significantly and independently related to Dukes' stage (p=0.000), postoperative stay (p=0.001), and blood transfusion (p=0.011). The mean postoperative stay for the 98 patients who later developed recurrence was 15 days compared to 12 days for the 243 patients who remained disease free (p=0.0008). Cumulative disease-free survival of the 142 patients who stayed more than the median of 11 days was 60% compared to 77% for the 199 patients with shorter stays (p=0.000). These data indicate that shorter hospital stays do not compromise disease-free survival of patients with colorectal cancer.