Biomedical subjects

G B Kristensen

Publications and source records attributed to G B Kristensen.

At least 19 recordsLinked to original sources

PubMed1996

Evaluation of the prognostic significance of cathepsin D, epidermal growth factor receptor, and c-erbB-2 in early cervical squamous cell carcinoma. An immunohistochemical study.

BACKGROUND: This study evaluated the prognostic significance of immunohistochemical staining for cathepsin D, epidermal growth factor receptor (EGFR), and c-erbB-2 in patients with early cervical squamous cell carcinoma. METHODS: This retrospective analysis comprised 132 patients, all subjected to radical hysterectomy with bilateral pelvic lymphadenectomy for International Federation of Gynecology and Obstetrics (FIGO) Stage IB cervical squamous cell carcinoma. Immunohistochemical staining was correlated with various histopathologic and morphologic characteristics (i.e., tumor size, grade of differentiation, vessel invasion, invasion into parametria, and lymph node metastasis) and relapse free survival. RESULTS: Positive staining for cathepsin D was observed in 47% of tumors, more frequent in tumors giving rise to lymph node metastases. The relapse free survival was lower for patients with cathepsin D positive tumors. Overexpression of EGFR was observed in 25.8% of the tumors. There was no correlation with any of the histopathologic variables investigated. Relapse free survival was lower for patients with tumors overexpressing EGFR. Immunohistochemical staining for c-erbB-2 was observed in 12.1% of tumors with no correlation with relapse free survival. In multivariate analysis, immunostaining of cathepsin D and EGFR obtained independent prognostic significance, and considered together (both negative, one positive, or both positive) was the strongest prognostic factor after tumor size. CONCLUSIONS: Immunohistochemical staining for cathepsin D and EGFR is useful as a tool for evaluation of tumor aggressiveness in patients with early cervical squamous cell carcinoma.

Carcinoma, Squamous Cell↗

PubMed1996

Cisplatin/5-fluorouracil treatment of recurrent cervical carcinoma: a phase II study with long-term follow-up.

OBJECTIVE: To evaluate the response rate and corrected survival in patients with recurrent cervical carcinoma (RCC) treated with 100 mg/m2 cisplatin (CDDP) i.v. on Day 1 and 1000 mg/m2 5-fluorouracil (5-FU) i.v. on Days 1 to 5. METHODS: A phase II study of CDDP/5-FU in RCC was initiated in 1986. Up to December 1991, a total of 72 patients were enrolled. Of these, 65 were evaluable for response. RESULTS: The overall response rate was 49%. For 9 patients with complete remission, the median duration of response was 16 months, range 6 to 79+. The corresponding figures for 26 patients with partial remission were 10 months, range 3 to 80 months. By multivariate analysis, FIGO stage, disease-free interval, WHO performance status, and number of lesions at recurrence were independent prognostic variables. Twenty-two percent of the patients survived for more than 2 years and 9% for more than 5 years. Toxicity was tolerable. Leucopenia, ototoxicity, and neurotoxicity were the main problems. CONCLUSION: A high response rate (49%) was observed with CDDP/5-FU treatment in patients with RCC with 9% of the patients surviving for more than 5 years.

Adult↗

PubMed1996

Malignant melanoma of the vulva FIGO stage I: Evaluation of prognostic factors in 43 patients with emphasis on DNA ploidy and surgical treatment.

Forty-three cases of malignant melanoma of the vulva FIGO stage I, primary treated from 1956 to 1987, have been reviewed. Initial surgery was local excision in 14 patients, vulvectomy in 14, and radical vulvectomy with inguinal lymph node dissection in 15. Recurrent disease was seen in 27 (63%) patients. The 5-year corrected survival was 63%; 10-year survival was 52%. Independent prognostic factors for disease-free and long-term survival were angioinvasion and DNA nondiploidy. Tumor thickness was of prognostic importance in univariate analysis, but did not obtain independent significance. Initial surgical modality did not influence long-term survival, but affected disease-free survival significantly. Local excision carried the greatest risk of local recurrence, but in some of these patients secondary surgery was successful. Because radical surgery did not improve long-term prognosis, wider local excision or vulvectomy seems to be the recommended surgical approach.

Adult↗

PubMed1996

Evaluation of the prognostic significance of nm23/NDP kinase protein expression in cervical carcinoma: an immunohistochemical study.

The objective of this study was to evaluate the prognostic significance of immunohistochemical staining for nm23/nucleoside diphosphate (NDP) kinase in cervical carcinoma. A retrospective analysis of 176 patients with cervical carcinoma FIGO stage IB treated with radical hysterectomy and pelvic lymphadenectomy from 1987 to 1990 was conducted. Immunohistochemical staining using the polyclonal nm23-H1/NDP kinase A antibody was correlated to various histopathological and morphological characteristics (tumor size, histologic type, grade of differentiation, vessel invasion, invasion into parametria, and lymph node metastasis) and relapse-free survival. For controls, sections were obtained from 10 hysterectomy specimens with normal cervical epithelium. Staining for nm23/NDP kinase was observed in 90% of control cases and in 70.5% of cases of cervical carcinoma, more frequent in squamous and adenosquamous cell carcinoma than in adenocarcinoma and more frequent in poorly differentiated than in more highly differentiated tumors. There were no differences related to size of tumor or invasion into vessels or parametria or occurrence of lymph node metastasis. The relapse-free survival was lower for patients with squamous cell and adenosquamous tumors with positive immunostaining for nm23/NDP kinase than for those with negative tumors when evaluated in univariate analysis. In multivariate analysis with tumor size, vessel invasion, invasion into parametria, grade of differentiation, and lymph node metastasis included, this difference was no longer significant. In patients with adenocarcinoma no difference was found. In conclusion, we did not find immunostaining for nm23/NDP kinase to be a useful indicator for prognosis in cancer of the uterine cervix.

Adenocarcinoma↗

PubMed1996

The prognostic significance of surgery, tumor size, malignancy grade, menopausal status, and DNA ploidy in endometrial stromal sarcoma.

To evaluate the prognostic significance of DNA ploidy in endometrial stromal sarcoma, the traditional clinical and histopathological prognostic variables and DNA ploidy in 48 patients with histologically verified endometrial stromal sarcoma were analyzed. Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the tumor were obtained in 47 patients. In univariate analysis, malignancy grade (P < 0.001), cellular atypia (P < 0.001), tumor diameter (P = 0.001), and mitotic count (P = 0.002) were highly significant. Also menopausal status (P = 0.011), FIGO stage (P = 0.035), and free resection margins at primary surgery (P = 0.026) obtained significance, while vessel invasion and age did not. DNA ploidy was not significant. In Cox multivariate analysis, free resection margins at primary surgery were found to be the most important prognostic factor (P < 0.001), followed by malignancy grade (P = 0.002), tumor diameter (P = 0.019), and menopausal status (P = 0.019). DNA ploidy did not obtain significance. Free resection margins at primary surgery, malignancy grade, tumor diameter, and menopausal status are important prognostic factors in endometrial stromal sarcoma.

DNA, Neoplasm↗

PubMed1996

Human papilloma virus has no prognostic significance in cervical carcinoma.

The prognostic significance of the detection of HPV (human papilloma virus) DNA in cervical carcinoma was evaluated in 223 cases treated from January 1988 to November 1989. HPV DNA was detected by PCR (polymerase chain reaction) on fresh tumour specimens obtained before therapy was started. HPV DNA of any type was detected in 93.3% of all tumours, HPV16 was the predominant type and was detected in 69% of cases. HPV18 was more frequent in adeno- and adenosquamous carcinoma than in squamous cell carcinoma and occurred more often in poorly differentiated tumours than in more highly differentiated tumours. Patients with HPV negative tumours were on average older than patients with tumours containing HPV. Neither presence of HPV DNA nor HPV type had prognostic significance. In 63 women with early stage tumours submitted to surgery, no difference was found in the frequency of lymph node metastasis, vessel invasion or prognosis related to HPV type. We conclude that neither the presence nor the type of HPV DNA had any prognostic significance in cervical carcinoma.

Adenocarcinoma↗

PubMed1995

Malignant melanoma of the vulva. Evaluation of prognostic factors with emphasis on DNA ploidy in 75 patients.

BACKGROUND: To the authors' knowledge, the potential prognostic value of DNA ploidy in vulvar melanoma has not been evaluated in previous series. METHODS: Clinical data and follow-up information were retrieved from the hospital records of 75 patients treated from 1956 to 1987. Histopathologic specimens were reviewed for histologic type, depth of invasion, vessel invasion, and ulceration. Flow cytometric DNA measurements were performed on paraffin embedded samples. RESULTS: Forty-three patients had International Federation of Gynecology and Obstetrics Stage I disease, 14 Stage II, 8 Stage III and 10 Stage IV. Sixty-five patients were treated by surgery, six by radiotherapy, and four patients with advanced disease received no therapy. The surgical procedure was local excision in 17 patients, vulvectomy in 22, and radical vulvectomy with inguinal lymph node dissection in 26. Five- and 10-year corrected survival rates were 46% and 37%, respectively. Recurrences were seen in 43 (66%) of the patients treated by surgery. Independent prognostic factors for corrected survival in the entire group of 75 patients were inguinal lymph node metastases (P = 0.016), angioinvasion (P = 0.027), tumor localization to clitoris, and multifocal tumors (P = 0.043). For the 65 patients treated by surgery, independent prognostic factors for disease free survival were angioinvasion (P < 0.001), age at diagnosis (P = 0.003), DNA ploidy (P = 0.004), and ulceration (P = 0.027). The independent prognostic factors for long term survival were tumor localization to clitoris (P = 0.018), DNA ploidy (P = 0.045), and inguinal lymph node involvement (P = 0.053). Radical surgery did not improve disease free or long term survival. CONCLUSIONS: DNA ploidy is an independent factor that predicts prognosis in patients with vulvar melanoma, and should be considered together with previously known factors. Radical surgery does not improve prognosis and is not recommended when the inguinal lymph nodes are clinically negative.

Adult↗

PubMed1995

The prognostic significance of residual disease, FIGO substage, tumor histology, and grade in patients with FIGO stage III ovarian cancer.

Survival was evaluated in 455 patients with FIGO stage III invasive ovarian cancer managed between 1983 and 1991. Median follow-up was 73 months. The prognostic significance of clinical and histopathological variables was evaluated. In Cox multivariate analysis, FIGO substage was an independent prognostic factor with a relative hazard (RH) of 1.2 and 1.7 for substage IIIB and IIIC, respectively (P = 0.013). Size of residual disease after surgery was a stronger factor with an RH of 1.2 and 2.4 for residual disease of 0 to 2 cm and more than 2 cm, respectively (P < 0.001). Histologic type had prognostic significance because patients with endometrioid tumors did best, those with mixed, serous, and unclassified tumors had an RH of 1.5 to 1.9, and those with mucinous and clear cell tumors had an RH of 5.4 to 7 (P < 0.001). Grade, ascites, and age had also independent significance. Grade had an RH of 2.5 for grade 2 plus 3 (P < 0.001), ascites had an RH of 1.4 (P 0.018), and age had an RH of 1.7 and 2.4 for age 40 to 70 years and above 70 years, respectively (P < 0.001).

Adult↗

PubMed1995

No prognostic impact of flow-cytometric measured DNA ploidy and S-phase fraction in cancer of the uterine cervix: a prospective study of 465 patients.

In a prospective study of 465 patients with invasive carcinoma of the uterine cervix, the prognostic impact of flow cytometric parameters (ploidy level and fraction of S-phase cells) and clinical variables was evaluated. Median follow-up time was 57 (32-80) months. A total of 230 patients died of cervical cancer during follow-up. Ploidy level had no prognostic significance, neither when analyzed as diploid against nondiploid nor when utilizing different cutoff levels for DNA index (1.3, 1.5, and 1.7). The fraction of S-phase cells (SPF) could be evaluated in 91% of the diploid cases but in only 22% of nondiploid cases. SPF had no prognostic impact. In multivariate analysis, FIGO stage was the only independent prognostic factor (P < 0.001). There was no difference between squamous cell, adeno, and adenosquamous carcinomas. A radical hysterectomy with pelvic lymphadenectomy was performed in 123 cases in stage I-IIA. In this subgroup, tumor size (P = 0.001), infiltration into the parametria (P = 0.005), vessel invasion (P = 0.008), and metastasis to the common iliac nodes (P = 0.013) obtained independent statistical significance in multivariate analysis, while ploidy level had no significance. Neither DNA ploidy nor S-phase analyses should be used in treatment planning.

Adenocarcinoma↗

PubMed1995

A phase II study of carboplatin and hexamethylmelamine as induction chemotherapy in advanced epithelial ovarian carcinoma.

27 patients with ovarian cancer FIGO stages IIc-IV were treated with carboplatin 7 x (glomerular filtration rate + 25) mg given intravenously on day 1 and hexamethylmelamine (HMM) 150 mg/m2 orally on days 2-15, every 28 days. 3 patients were not evaluable for response. Clinical response was seen in 17 patients (71%), with six (25%) complete and 11 (46%) partial responses. The median progression-free survival was 15.6 months and the median cancer-related survival was 21.3 months. 4 patients (15%) experienced grade 3 mental depression; none had peripheral neuropathy above grade 1. The haematological toxicity was moderate, none had grade 4 leucopenia, but 4 (15%) had grade 4 thrombocytopenia. Carboplatin plus HMM had few side-effects and a high response rate with a survival comparable to other platinum-based combinations.

Adult↗

PubMed1995

The prognostic significance of stage, tumor size, cellular atypia and DNA ploidy in uterine leiomyosarcoma.

To analyze the significance of DNA ploidy in uterine leiomyosarcoma, the traditional clinical and histopathological prognostic variables and DNA ploidy were studied in 70 patients with histologically verified uterine leiomyosarcoma. Evaluable flow cytometric DNA histograms from paraffin-embedded tissue from the tumor were obtained in 58 patients. In univariate analysis tumor diameter, FIGO stage and presence of residual disease after primary surgery were highly significant (p < 0.001) and also DNA ploidy (p = 0.043), age (p = 0.017), and menopause status (p = 0.028) obtained significance. Cellular atypia was almost significant (p = 0.056), while mitotic count, malignancy grade and vessel invasion were not. In Cox's multivariate analysis, FIGO-stage was found to be the most important prognostic factor (p < 0.001), followed by cellular atypia (p = 0.007) and tumor diameter (p = 0.016). DNA ploidy did not obtain significance when categorized as diploid/non-diploid. Patients with tumors with multiple aneuploid cell populations had a very poor prognosis. When categorized as multiple aneuploidy versus all other ploidy groups, DNA ploidy obtained marginal significance in multivariate analysis (p = 0.054). Tumor diameter, stage and cellular atypia are important prognostic parameters in uterine leiomyosarcomas.

Adult↗

PubMed1994

Flow cytometric DNA ploidy and S-phase heterogeneity in advanced ovarian carcinoma.

BACKGROUND: The prognostic significance of flow cytometric DNA ploidy and S-phase fraction (SPF) in ovarian cancer has been controversial. In the current study, the authors analyzed tumor heterogeneity in respect to DNA index DI and SPF. METHODS: Flow cytometric variation in DI and SPF among representative fresh tumor material from the primary tumor, metastasis, and malignant effusions from the same patient was analyzed. RESULTS: One hundred thirty-two samples from 47 patients were analyzed, and 119 samples from 42 patients were evaluable. Stable DI between different samples was found in 34 patients, whereas heterogeneity was found in 8 patients (19%). The metastases showed stable DNA content. The malignant effusion samples often lacked tumor cells. The representative ones were often DNA diploid. In 21% of the aneuploid samples, the SPF could not be analyzed. In 38% of the aneuploid samples, the stem line constituted less than 15% of measured nuclei. In these samples, a negative correlation between SPF and percentage of aneuploid cells was found, making SPF unreliable. Correct SPF measurement was thus possible in only 41% of the aneuploid samples, and in these tumors, SPF values varied considerably among different samples from the same patient, illustrated by a median SPF difference of 11% (range, 0-28%). CONCLUSIONS: Tumor DI heterogeneity existed in 19% of tumors. SPF depended on the amount of aneuploid cells in case of small stem lines and varied considerably, making its use as a prognostic factor doubtful. To ensure that all tumor stem lines are represented, at least two biopsy specimens from any solid tumor should be analyzed.

Adult↗

PubMed1994

A randomised study of cisplatin versus thiotepa as induction chemotherapy in advanced ovarian carcinoma.

Between 1980 and 1984, a total of 171 patients with advanced epithelial ovarian carcinoma and residual tumour after surgery were randomly assigned to treatment groups receiving either cisplatin or thiotepa. The objective of the study was to evaluate the regimes with regard to response and survival. The two groups were well balanced with respect to age, FIGO stage, histology, grade and residual tumour after surgery. In the cisplatin group, 66% responsed to treatment compared to 38% in the thiotepa group (P < 0.00005). The median progression-free survival was 10.5 months and 6.3 months, respectively. The corrected survival was somewhat, but non-significantly, higher in the cisplatin group than in the thiotepa group, with an 8-year corrected survival of 10.6 and 7.4%, respectively. In a multivariate analysis, based on progression-free survival with FIGO stage, residual tumour after surgery, histological type and grade as covariables, treatment with thiotepa had a relative risk of 1.64 compared to cisplatin (95% confidence interval 1.17-2.30, P = 0.004).

Adult↗

PubMed1994

Evaluation of deoxyribonucleic acid ploidy and S-phase fraction as prognostic parameters in advanced epithelial ovarian carcinoma: a prospective study.

OBJECTIVE: Our goal was to study the prognostic value of deoxyribonucleic acid ploidy and S-phase fraction in advanced ovarian carcinoma. STUDY DESIGN: Prognostic factors for corrected survival were evaluated in a prospective study including 169 patients with stage III and IV ovarian cancer treated between 1985 and 1990. RESULTS: A total of 79% of the tumors were deoxyribonucleic acid aneuploid. Deoxyribonucleic acid aneuploidy was associated with grade of differentiation. S-phase fraction could be calculated in all deoxyribonucleic acid euploid tumors and 76% of the deoxyribonucleic acid aneuploid tumors. By multivariate analysis deoxyribonucleic acid ploidy, histologic type and grade, age, International Federation of Gynecology and Obstetrics stage, and amount of residual tumor were independent prognostic variables for corrected survival. On the basis of Cox regression a relative risk for the individual patient could be calculated. CONCLUSION: Deoxyribonucleic acid ploidy gives additive prognostic information and is a useful parameter for dividing patients with advanced ovarian cancer into risk groups for treatment decisions.

Adult↗

PubMed1993

Is serum CA 125 at the time of relapse a prognostic indicator for further survival prognosis in patients with ovarian cancer?

The prognostic significance of serum CA 125 level before treatment of relapse for invasive epithelial ovarian cancer has been evaluated in 135 patients. At time of relapse, serum CA 125 level was higher than 35 U/ml in 110 (82%) patients. Those with serum CA 125 level of 35 U/ml or less at relapse had a better prognosis than those with higher values. Among patients with serum CA 125 level higher than 35 U/ml no difference in survival was observed. By multivariate analysis the independent prognostic factors for survival were histologic type (P < 0.0001) and serum CA 125 level (P < 0.01). Randomized trials are needed to further evaluate whether early detection of disease relapse because of serial serum CA 125 measurements does have prognostic significance.

Abdominal Neoplasms↗

PubMed1993

Serum CA 125 level allows early identification of nonresponders during induction chemotherapy.

CA 125 was measured during induction chemotherapy in 119 patients with advanced epithelial ovarian cancer who had residual disease after primary surgery in order to determine whether patients with poor response to further treatment could be identified during early chemotherapy. All patients had a prechemotherapy serum CA 125 level higher than 35 U/ml. Blood samples were further obtained 4 weeks after the first, second, and third course. Four weeks after the second course of chemotherapy, all 20 patients with PCR, or microscopic disease at second-look, all 17 who achieved complete clinical remission, and 36 of 40 who achieved partial remission had serum CA 125 of 65 U/ml or less or had a decrease of 50% or more of the prechemotherapy level. Survival analysis showed that patients with a serum CA 125 level of 65 U/ml or less 4 weeks after the second course of chemotherapy had the best prognosis. In patients with a serum CA 125 level higher 65 U/ml at that time, a decrease of 50% or more of the prechemotherapy level indicated a prognosis better than that with a lesser decrease. The combined criteria for serum CA 125 (level > 65 U/ml 4 weeks after the second course and a decrease < 50% of the prechemotherapy level) allowed for identification of a real high-risk group with a median survival of 8.9 months and was identified by Cox regression multivariate analysis as the most powerful indicator for survival (P < 0.0001).

Adult↗

PubMed1993

Evaluation of endometrial thickness measured by endovaginal ultrasound in women with postmenopausal bleeding.

Endovaginal ultrasound scanning was used preoperatively in 100 women with postmenopausal vaginal bleeding referred for dilatation and curettage. The ultrasonographic appearance of the endometrium was related to the histologic diagnosis. Endometrial malignancy was found in 15 patients, in 2/45 (4.4%) of women aged less than 60 years and in 13/55 (23.6%) of women aged 60 years or more. Out of 54 patients with an endometrial thickness of less than 5 mm as measured by ultrasound, 3 had an endometrial malignancy, and 12 of 45 with an endometrial thickness of 5 mm or more, had an endometrial malignancy. The sensitivity of ultrasound to detect malignancy was 80%, the specificity was 60%, the positive and negative predictive values were 26% and 94.4%. The sensitivity and the negative predictive value was not high enough to replace histologic examination of the endometrium.

Adult↗

PubMed1992

CA 125 measured before second-look laparotomy is an independent prognostic factor for survival in patients with epithelial ovarian cancer.

The prognostic significance of serum CA 125 level measured in the week before second-look operation was evaluated in 208 patients with invasive epithelial ovarian cancer. Serum CA 125 level was greater than 35 U/ml in 44.7% of patients. All patients with pathological complete response (PCR) had a serum CA 125 level less than or equal to 35 U/ml except one who developed lung metastases 2 months later. The sensitivity of serum CA 125 for identifying residual tumor at second-look operations was 58%, the specificity was 98%, the predictive value of a positive test was 99%, and the predictive value of a negative test was 43%. By Cox regression analysis, tumor state of second look, serum CA 125 level, histologic type, FIGO stage, and tumor grade were identified as independent prognostic factors for survival. We conclude that measurement of serum CA 125 level after induction chemotherapy represents a noninvasive method to identify patients at high risk for subsequent death from ovarian cancer. As far as we know, this is the first report to identify serum CA 125 level as an independent prognostic factor at the time of second-look laparotomy.

Actuarial Analysis↗