Effects of systemic and regional chemotherapy after hepatic resection for colorectal metastases

BACKGROUND: Although the survival benefit of hepatic resection for colorectal metastasis has been established, some controversy remains regarding the significance of adjuvant chemotherapy after hepatic resection. METHODS: One hundred thirty-two consecutive patients who had liver resection for colorectal metastasis at our hospital between 1980 and 1997 were studied. After curative hepatic resection, 37 patients underwent systemic chemotherapy, administered orally or intravenously, and 38 patients underwent regional chemotherapy, given intra-arterially or intraportally. Forty patients had no adjuvant chemotherapy. The chemotherapeutic agents used for oral administration were uracil and Tegafur or Tegafur alone. Mitomycin C (MMC) or 5-FU was used for IV chemotherapy. Combinations of 5-FU/leucovorin or MMC/5-FU (doxorubicin) were used for regional chemotherapy. Univariate and multivariate analyses were applied to test the significance of adjuvant chemotherapy for patient survival or disease-free survival. RESULTS: Overall 5-year survival was 42.2% (95% CL: 31.2%, 53.2%). Among the possible prognostic factors studied, univariate analysis showed a significant difference in survival based on the number of tumors and lymph node metastases in the hepatic hilum. There was a significant difference in disease-free survival based on adjuvant chemotherapy and lymph node metastasis. The multivariate analysis for patient survival selected four prognostic factors (P < .05), including adjuvant chemotherapy, lymph node metastasis, disease-free interval, and tumor size. The multivariate analysis for disease-free survival selected adjuvant chemotherapy, lymph node metastasis, and disease-free interval as significant factors. The most common recurrence site was remnant liver, regardless of adjuvant chemotherapy. CONCLUSIONS: Adjuvant chemotherapy significantly improved survival and disease-free survival after hepatic resection for colorectal metastases. It did not decrease recurrence rate in the remnant liver.     

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.     

Prognostic factors in uterine sarcomas: a 21-year retrospective study at the Clinic and Provincial Hospital of Barcelona

BACKGROUND: Uterine sarcomas show low incidence and poor outcome despite the treatment. The prognostic factors for the survival were determined in this study. PATIENTS AND METHODS: Thirty-nine females with sarcoma of the uterus have been studied retrospectively from January 1975 to December 1996. They were treated in the Gynecology and Radiation Oncology Departments at Hospital Clínic i Provincial of Barcelona. Thirty-seven patients had surgery, 22 radiotherapy and 4 chemotherapy. The influence on the disease-specific survival, disease-free survival, local relapse disease-free survival and metastasis disease-free survival from the following pronostic factors was studied: age, pathologic subtype, miometrial invasion, mitosis, vascular and lymphatic invasion, tumor size, stage, radiotherapy and local relapse. RESULTS: 1) The disease-specific survival at 2 and 5 years was 51.5% and 42.5% respectively, and the disease-free survival at 2 and 5 years was 39%; the incidence of local and distant relapses--was 28 and 33%. 2) The multivariate analysis showed that the overall survival and the disease free survival were affected by the vascular invasion (odds ratio [OR] 12 and 32.6, respectively) and the local failure (OR = 3 and 25.5, respectively); the only factor that affected the local relapse-free survival and metastasis free survival was the III and IV stages (OR = 5.6 in both cases). CONCLUSIONS: In uterine sarcomas, the vascular invasion and the local relapse were prognostic factors for overall survival and for disease-free survival. In stages III and IV there was a decrease in the local relapse-free survival and metastasis-free survival. A correlation between vascular invasion and advanced stages was found. The outcome of the uterine sarcomas is poor, local and distant failure being responsible for this bad prognosis.     

P53 overexpression in head and neck carcinoma and radiotherapy results

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p < 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.     

Sensitization of olfactory guanylyl cyclase to a specific imprinted odorant in coho salmon

PURPOSE: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. METHODS AND MATERIALS: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. RESULTS: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). CONCLUSION: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and may improve overall survival in certain subgroups. As salvage rates after developing local recurrence are poor adjuvant vulvar radiation should be considered for patients at risk after primary surgery.     

DNA loop domains in a 1.4-Mb region around the human hprt gene mapped by cleavage mediated by nuclear matrix-associated topoisomerase II

The aim of the study was the definition of the clinical features and survival of 27 resected cases of distal bile duct carcinoma. This neoplasm accounted for 14% of all periampullary malignancies treated by pancreaticoduodenectomy between 1990 and 1996. Jaundice was present in 96% of patients, but was the first symptom only in 78%. Preoperative investigations allowed to recognize distal bile duct cancer in a minority of patients (41%). Operative mortality and morbidity were 3.7 and 44%, respectively. Most patients (88%) were assigned to UICC stage IV-A. Postoperative survival was not significantly better than survival of 101 patients undergoing pancreaticoduodenectomy for pancreatic ductal carcinoma; median survival was 22 months, with a 13% 5-year survival rate. Determinants of a better prognosis were UICC stage 相似文献   

The human lysyl oxidase-related gene (LOXL2) maps between markers D8S280 and D8S278 on chromosome 8p21.2-p21.3

OBJECTIVE: bcl-2 is a protein which prohibits programmed cell death. The purpose of this study was to determine whether bcl-2 staining was related to traditional prognostic factors and/or recurrence in patients with endometrial carcinoma. METHODS: One hundred twenty consecutively surgically treated patients with endometrial carcinoma had their tumors studied immunohistochemically for bcl-2 staining. RESULTS: The mean follow-up of the patients was 53 months with a median of 56 months (range 30 to 68 months). bcl-2 staining was positive in 44.0% of patients with endometrioid carcinomas and in 23. 1% of patients with nonendometrioid carcinomas (P < 0.001). Increasing depth of invasion (P = 0.014), grade (P = 0.011), and FIGO stage (P = 0.018) were each correlated with decreasing bcl-2 staining. bcl-2 staining was positive in 44.1% of patients whose tumors showed no lymphovascular space invasion and in 11.1% of patients with lymphovascular space invasion (P < 0.001). Only 1 of 26 patients with recurrent disease had persistence of bcl-2 staining. Multivariate analysis revealed FIGO stage (P = 0.0051), histologic grade (P = 0.050), and lack of staining for bcl-2 (P = 0.012) to be independent predictors of recurrence. CONCLUSION: bcl-2 persistence is more common in endometrioid than in nonendometrioid adenocarcinomas of the endometrium. It appears to be inversely correlated with the universally recognized prognostic factors of depth of invasion, histologic grade, and FIGO stage. Lack of bcl-2 persistence was an independent predictor of recurrence of disease. This group of patients continues to be followed to determine the role of bcl-2 persistence or lack of persistence as a predictor of 5-year survival of patients with endometrial carcinoma.     

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.     

Stage I rectal cancer: identification of high-risk patients

BACKGROUND: Stage I rectal cancer (T1, T2 N0) is currently treated by surgical resection alone. Despite adequate surgical resection, approximately 10-15% of patients will develop recurrence. Identification of patients at high risk for recurrence could potentially lead to an improvement in outcome by selection of these patients for adjuvant therapy. METHODS: Between June 1986 and September 1996, 211 patients with primary rectal cancer (stage I) were treated by radical surgical resection alone. The medical data of all patients were entered into a database and prospectively followed. The following 10 prognostic factors were correlated with recurrence and tumor-related mortality: patient factors: age, gender, and preoperative carcinoembryonic antigen level; tumor factors: location from the anal verge (< 6 cm vs. > or = 6 cm), T stage (T1 vs. T2), intratumoral blood vessel invasion (BVI), intratumoral lymphatic vessel invasion, presence of tumor ulceration, and histologic differentiation; and treatment-related factors: extent of surgical resection--abdominal perineal resection versus low anterior resection. Univariate analysis of the effect of the prognostic factors on recurrence and tumor-related mortality were performed by the method of Kaplan-Meier and log rank test. Independent prognostic factors were determined by a multivariate analysis performed using the Cox proportional hazards model. RESULTS: The overall 5-year actuarial recurrence was 12% and tumor-related mortality was 10%. Independent predictors of recurrence were male gender and BVI. Independent predictors of tumor-related mortality were male gender, BVI, and poorly differentiated tumors. CONCLUSIONS: Despite radical resection, patients with stage I rectal cancer with male gender, BVI, and poorly differentiated tumors should be considered high-risk patients.     

The accuracy of staging: an important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis

BACKGROUND: Several prognostic factors for stage I ovarian carcinoma have been analyzed. Some of them are biological and clinical in nature, but others such as the thoroughness of the staging procedure, the extent of the surgery and the philosophy of treatment, are defined by the human element. PATIENTS AND METHODS: We reviewed the records of 351 patients with Stage I ovarian cancer who had been treated from 1981 to 1991. For all patients the following information was available: age, size of the tumor, FIGO sub-stage, tumor grade, histologic type, rupture of the tumor, cytology, extent of the staging and of the surgery (hysterectomy and bilateral salpingo-oophorectomy vs. fertility-conserving surgery) and use of adjuvant treatments. The thoroughness of the staging was defined as: optimal staging: total abdominal hysterectomy and bilateral salpingo-oophorectomy or fertility-conserving surgery, peritoneal cytology or washing, omentectomy, multiple peritoneal biopsies, sampling of the retroperitoneal nodes or formal lymphadenectomy, peritoneal staging: all the criteria described above were met with the exception of retroperitoneal sampling, incomplete staging: lack of any of the previously-cited criteria. RESULTS: An optimal staging was performed in 100 patients, a peritoneal staging in 107 and an incomplete staging in 144. Radical surgery was performed in 295 women and fertility-conserving surgery in 56. With a median follow-up of 108 months (range 14-184) 64 patients had recurrence of the tumor. Fifty-three died of the disease, two are currently alive with disease and nine were salvaged by surgery and/or chemotherapy. In a multivariate analysis only the tumor grade and the type of staging were significant independent prognostic factors for both disease-free and overall survival. CONCLUSIONS: As described by other authors, we confirm that tumor grade is the single most important biological prognostic factor in early ovarian carcinoma. The thoroughness of the staging impacts significantly on survival, particularly in poorly differentiated carcinomas. Fertility-sparing surgery is not associated with a worse outcome than standard radical surgery.     

Is total abdominal hysterectomy with bilateral salpingo-oophorectomy adequate for new FIGO stage I endometrial carcinoma?

OBJECTIVE: The new FIGO staging for endometrial cancer cases complies with other forms of surgical staging and correlates better with clinical outcomes because it includes prognostic factors. This study was done to investigate whether total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH+BSO) is adequate for new FIGO Stage I endometrial carcinoma. SUBJECTS: Sixty-five cases of endometrial carcinoma defined according to the new FIGO Stage Ia (n = 26), Ib (n = 24) and Ic (n = 15) were analysed. They all received TAH+BSO only and were followed up for at least two years. METHODS: The histologic type, grade, depth of myometrial invasion, lympho-vascular tumour emboli and tumour size were analysed by t-test to correlate the risk factors for treatment failure. RESULTS: There were no recurrences after TAH+BSO in Ia and Ib cases. However, recurrences occurred in five cases (33%) of Stage Ic with deep myometrial invasion, high histologic grade, large tumour size and tumour emboli. CONCLUSIONS: TAH+BSO is inadequate in some Ic cases with a high histologic grade, deep myometrial invasion and tumour emboli. Thus, thorough pre-operative and intra-operative staging, adequate operation method and prompt post-operative adjuvant therapy are indispensable for successful treatment.     

Effects of intracerebroventricular administration of beta-funaltrexamine on DAMGO-stimulated [35S]GTP-gamma-S binding in rat brain sections

In a retrospective study, a total of 120 ovarian cancer patients were paired in terms of staging, grading, patent age, and operative and cytostatic therapy. Half of the patients underwent radioimmunoscintigraphy for diagnostic purposes. From the point of view of possible adjuvant immunological therapy, we investigated to what extent patients with treated ovarian cancer benefit from the application of OC 125 in terms of survival time. In our study we have been able to show that at favorable stages (FIGO II) the patient benefitted more from a radioimmunoscintigraphy than at prognostically unfavorable stages (FIGO IV). Even within FIGO stage III we have been able to show, thanks to the large number of cases, that patients with an NED situation benefitted significantly more form radioimmunoscintigraphy in terms of survival than those with residual tumors. Throughout FIGO stage III, patients with radioimmunoscintigraphy showed significantly superior 5-year survival rates (p < 0.05) than those without radioimmunoscintigraphy. These data would appear to justify prospective studies to establish to what extent ovarian cancer patients benefit from an adjuvant application of OC 125 in terms of the 5-years survival rate and the relapse-free interval.     

Adenocarcinoma in the middle third of the stomach--an evaluation for the prognostic significance of clinicopathological features

BACKGROUND/AIMS: The prognosis of patients with gastric adenocarcinoma varies with the location of the tumor. Adenocarcinoma in the middle third of the stomach has been claimed to have a better outcome than those in other locations. However, there is still very limited information specifically regarding the prognostic factors which influence the survival time of patients with adenocarcinoma in the middle third of the stomach. This retrospective study was designed with the aim to evaluate and uncover the possible significant clinicopathological parameters for adenocarcinoma in the middle third of the stomach. METHODOLOGY: Between 1986 and 1992, 363 patients underwent gastric resection for primary gastric adenocarcinoma at this hospital. Fifty-two (14.3%) of these patients were included in this study and they all met the following criteria: 1) tumor primarily located in the middle third of the stomach without distant metastases or peritoneal seeding, 2) undergoing curative resection and 3) undergoing R2 nodal dissection, at least. The clinicopathological findings were obtained by detailed review of the medical records and the histologic slides. All surviving patients were also contacted and their current conditions were recorded. RESULTS: The overall 5-year survival rate (Kaplan-Meier method) was 42.5%. In univariate survival analysis by Kaplan-Meier method and long-rank test, serosal invasion (p < 0.01), lymph node metastasis (p < 0.01) and lymphatic involvement (p < 0.01) had an individual prognostic significance. When a multivariate analysis using Cox proportional hazards regression was performed, serosal invasion (P < 0.01) and lymphatic involvement (p < 0.05) appeared as the only two independent prognostic factors regarding long-term survival. When these 52 patients were categorized into patients with early gastric cancer (n = 10) and patients with advanced gastric cancer (n = 42), there was a significant difference (p < 0.01) between the survival rates (90.0% vs. 29.1%). When these tumors were further categorized into early gastric cancer (n = 10), early simulating advanced gastric cancer (n = 14) and Borrmann type advanced gastric cancer (n = 28), there were significant differences (P < 0.01 and P < 0.01, respectively) in 5-year overall survival rates between early gastric cancer (90.0%) and Borrmann type advanced gastric cancer (18.9%), also between early simulating advanced gastric cancer (52.5%) and Borrmann type advanced gastric cancer (18.9%). UICC stage also had significant influence (P < 0.01) on the survival rates. CONCLUSIONS: Serosal invasion and lymphatic involvement are the significant, independent prognostic factors in predicting the survival rate of patients with adenocarcinoma in the middle third of the stomach. Since more advanced stage tumors usually carry a poorer prognosis, early detection is of extreme importance for improving the survival rate.     

Impact of radiation therapy fraction size on local control of early glottic carcinoma

PURPOSE: Different radiotherapy fractionation schedules were used over a 10-year period to treat patients with early squamous cell carcinoma of the vocal cords at McGill University. A retrospective analysis was performed to study the effect of fraction size on local control in this group of patients. METHODS AND MATERIALS: A total of 126 previously untreated patients with T1 invasive squamous cell carcinoma of the true vocal cords were irradiated between January 1978 and December 1988 in the Department of Radiation Oncology at McGill University. All patients received megavoltage irradiation, 94 patients received daily fractions > 2 Gy (64 patients received 50 Gy with once-daily 2.5-Gy fractions, and 30 received 65.25 Gy in 29 fractions of 2.25 Gy each), and 32 patients were treated to a dose of 66 Gy in 33 fractions with 2 Gy/fraction. Patients' characteristics of prognostic importance were equally distributed between the two fractionation groups. RESULTS: At a median follow-up of 84 months, the 10-year disease-free survival and overall survival were 76% and 93%, respectively. Local control for patients treated with > 2 Gy fraction was 84%, compared to 65.6% for those treated with 2-Gy fractions (p = 0.026). Among the prognostic factors tested, such as gender, age, stage, anterior and posterior commissure involvement, smoking history, and fraction size, the latter was the only significant predictor of local control for the whole group of patients in univariate (p = 0.041) and multivariate (p = 0.023) analysis. There was no observed difference in the incidence of complications between the two fractionation groups. CONCLUSIONS: From the results of this retrospective review of patients treated with radiotherapy for T1 true vocal cord cancer, and within the range of total doses and overall treatment times used in our patients, it was found that fractionation schedules using daily fraction size > 2 Gy are associated with a better local control than schedules delivering 2 Gy/fraction, with no increase in toxicity.     

Angiotensin-1-converting enzyme (ACE) gene polymorphism, plasma ACE levels, and their association with the metabolic syndrome and electrocardiographic coronary artery disease in Pima Indians

Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in those patients with histological evidence of "risk" features--lymph node metastases, lymphatic vascular tumour permeation and clinically undetected parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy. One hundred and eight patients (45.2%) had various poor prognostic histological features and received adjuvant chemotherapy--70 had cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk factors present in each group were identical. These patients have now been followed up for periods ranging from 8 to 14 years. All recurrences, except one, occurred within 23 months of surgery; in the remaining this occurred 8 years later. This suggests that very close long-term follow-up is needed. Recurrences were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The 10-year survival in patients without risk factors was 97.2%. In those patients with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year survivals in patients with positive nodes were similar--66.7% in the MMC group and 71.4% in the PVB group. The 10-year survival in patients with squamous cell carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU) group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%) (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those with adenocarcinoma, the PVB regime.     

Prognostic factors for survival in patients with brain metastases from renal cell carcinoma

BACKGROUND: Patients presenting with brain metastases from renal cell carcinoma portend a poor prognosis, with a reported median survival of 4-6 months. Given their short life expectancy, these patients generally have been excluded from clinical trials that assess the efficacy of medical treatments. However, clinical impression suggests that some patients may achieve long term palliation. METHODS: The clinical features of 68 patients who were treated at the Institut Gustave Roussy for brain metastases from renal cell carcinoma were collected retrospectively. Using univariate and multivariate analyses, a prognostic model based on independent prognostic factors was established. An external data set of 57 patients was used to validate the model. RESULTS: The median survival was 7 months. On univariate analysis survival was related significantly to the following adverse prognostic factors: no initial nephrectomy, left side and temporal location of brain metastases, presence of fever or weight loss, erythrocyte sedimentation rate > 50 mm/h, and time from initial diagnosis to brain metastases < or = 18 months. Multivariate analyses identified the previous variable as well as the presence of other visceral metastases as independent prognostic factors. Forty-four patients (65%) with no or 1 adverse prognostic factor (average risk group) had a median survival of 8 months and a 26% 1-year survival rate. Twenty-four patients (35%) with 2 adverse prognostic factors (poor risk group) had a median survival of 3 months and a 1-year survival rate of 9%. This model proved to be discriminant in an external data set; the median survival of patients assigned to the average risk group was 11 months (46% 1-year survival rate) compared with 4 months (9% 1-year survival rate) for patients assigned to the poor risk group. CONCLUSIONS: Patients presenting with brain metastases from renal cell carcinoma and poor risk prognostic factors are highly unlikely to benefit from medical treatments except symptomatic procedures. Conversely, the enrollment of patients with average risk prognostic factors into clinical trials dealing with chemotherapy or immunotherapy may be considered.     

Characterized allergens causing bakers'' asthma

OBJECTIVE: Surveillance after orchiectomy alone becomes popular for the management of clinical stage I nonseminomatous germ cell testicular tumours (CS I NSGCTT). Effort to identify patients at high risk of relapse leads to searching prognostic factors of CS I NSGCTT. The aim of this study was to identify those patients in whom a surveillance policy is less likely to be successful. PATIENTS AND RESULTS: Seventy-two CS I NSGCTT patients were stratified to different risk-adapted therapeutic approaches according to histopathologic findings of primary tumor removed by inguinal orchiectomy. Eighteen patients (group A) with vascular invasion and majority of embryonal carcinoma component in the primary tumor were treated with adjuvant BEP chemotherapy. None of them experienced disease progression after a median follow-up period of 36 months after orchiectomy. Five patients (group B) with vascular invasion and the majority of teratomatous elements in the primary tumor have been followed up 56 months after orchiectomy. They were treated with primary retroperitoneal lymph node dissection (RPLND). Two of them (40%) had pathologic stage II after RPLND and underwent subsequent chemotherapy. One of them died due to disease progression 29 months following orchiectomy. Another one lives with no evidence of disease (NED). Three patients in pathologic stage I are alive with NED. Forth-nine patients (group C) without vascular invasion have been followed up for a median duration of 37 months after orchiectomy. They were kept under close surveillance, consisted of regular follow-up with tumor markers, chest x-ray and CT of the retroperitoneum. Disease progression was observed in 7 (14.3%) patients after a median duration of 8 months after orchiectomy. They were treated with BEP chemotherapy and live with disease-free median survival of 22 months after completion of therapy. The overall survival rate of all 72 patients was 98.6%. The median survival for all patients was 37 months (range 7-73). CONCLUSIONS: The authors will continue to use surveillance policy only in patients without vascular invasion in the primary tumor.     

Characterization of the Ca2+ -dependent and -independent interactions between calmodulin and its binding domain of inducible nitric oxide synthase

We reviewed the prevalence of thrombocytosis (platelet count >/=400, 000/microL) and its association with outcome in 135 consecutive endometrial carcinoma patients and compared the platelet count with other prognostic factors. Nineteen of 135 patients (14%) had thrombocytosis. Thrombocytosis was significantly more frequent in advanced disease (stage II-IV), unfavorable grade (G2 and G3), deep myometrial invasion, and lymph-vascular space invasion. The overall 5-year survival rate was 92%. The 5-year survival rate of the 19 patients with thrombocytosis was significantly worse than that of the patients without thrombocytosis (61 vs 96%, P < 0.0001). The recurrence rate was significantly higher in patients with thrombocytosis than in those with a platelet count <400,000/microL (7 vs 32%, P < 0.005). In a multivariate analysis, thrombocytosis continued to be a predictor of worse prognosis. In conclusion, we found thrombocytosis to be a prognostic factor for survival in patients with endometrial carcinoma.     

Carcinoma of the nasopharynx in young patients

PURPOSE: To provide an analysis of eighteen cases of adolescent nasopharyngeal carcinoma treated between 1971 and 1989. METHODS AND MATERIALS: Between 1971 and 1989, 48 cases of nasopharyngeal carcinoma were evaluated at the Medical College of Georgia Hospital and Clinics. Eighteen patients between the ages of 9 and 29 years were treated at the Georgia Radiation Therapy Center. All patients presented for treatment with (AJCC) Stage IV disease. Fifteen patients with lymphoepithelioma and three with squamous cell carcinoma histologies received definitive radiation therapy to a median dose of 64.8 Gy. Males outnumbered females by more than 2:1 and the majority of patients (67%) were black. Nine patients received multiagent adjuvant chemotherapy. RESULTS: Thirteen patients are alive from 7 to 166 months (median 32 months) including three with disease at 17, 24, and 132 months. Overall and disease-free survival at 5 and 10 years were 63% and 54%, respectively. Five patients died from disease; four patients had pulmonary metastases while one had CNS metastasis. Eighty percent of relapses occurred within the first 2 years following treatment. Acute and chronic toxicities were limited, consisting primarily of mucositis and xerostomia. Radiation doses of 65 Gy or more (p = 0.049) and age greater than 20 years (p = 0.005) were positive prognosticators for survival. Adjuvant chemotherapy, race, and sex were not found to be of prognostic value. Disparities in the distribution of patients with lymphoepithelioma and squamous cell histologies and the presentation of advanced regional disease precluded analysis for prognostic significance of histology and nodal status in this series. CONCLUSION: The results of the present series compare favorably with those published from other institutions. High doses of radiation and a high systemic failure rate continue to be the fundamental obstacles to effective management and enhanced survival for patients with nasopharyngeal carcinoma.     

A prospective study of prognostic value of type IV collagenase activity in colorectal cancer tissue

The purpose of this prospective study was to evaluate the prognostic value of the type IV collagenase (IVase) activity in colorectal cancer tissue on disease-free and overall survival in 31 colorectal cancer patients. The clinicopathologic factors studied for prognostic value were age, tumor location, tumor differentiation, preoperative serum levels of carcinoembryonic antigen, Dukes' stage, and IVase activity in colorectal cancer tissue. IVase activities in colorectal cancer tissue were significantly higher in the group of patients with recurrences than in the group without recurrences (P = 0.019). Patients with high IVase activity in colorectal cancer tissue had a significantly shorter disease-free survival (P = 0.0016) and overall survival (P = 0.022) time than those with low IVase activity. Univariate and multivariate analysis showed that significant prognostic factors for disease-free survival were Dukes' stage (P = 0.029, P = 0.046, respectively) and IVase activity status (P = 0.0016, P = 0.0026, respectively). With respect to overall survival, only IVase activity status provided significant predictive value in multivariate analysis (P = 0.041). This prospective study suggests that IVase activity is a valuable prognostic factor in colorectal cancer patients.