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A Ciavattini

Publications and source records attributed to A Ciavattini.

At least 19 recordsLinked to original sources
PubMed2000

Cisplatin, epirubicin and cyclophosphamide (PEC) in the treatment of advanced ovarian cancer.

We report the long-term results of a series of patients affected by advanced epithelial ovarian cancer treated with the PEC combination (cisplatin 60 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 750 mg/m2, all at day 1, every 21 days). Response was evaluated after three cycles, and treatment continued in responsive patients. A total of 80 patients with a median follow-up of 55 months were studied. Fifty-eight patients with stage III ovarian cancer and 22 patients with stage IV received PEC as primary treatment (41 patients), or for residual disease after surgery (37 patients), or for relapsed disease after primary surgery (2 patients). The overall response rate was 67.5% (20.0% complete response, 47.5% partial response), with 22.5% stable disease and 3.7% progressive disease. Median progression free survival was 13.0 months, and median survival was 25 months. Grade III-IV toxicity was moderate: leukopenia 20.0% of patients, thrombocytopenia 5.0%, anemia 16.2%. No cardiac toxicity was observed. In conclusion, the PEC combination, an anthracycline-containing platinum-based regimen, proved to be effective in advanced ovarian cancer, in terms of response rate and overall survival. The regimen was devoid of significant toxicity and in particular of cardiac toxicity.

Adult↗
PubMed1999

Expression of vascular endothelial growth factor related to 72-kilodalton metalloproteinase immunostaining in patients with serous ovarian tumors.

BACKGROUND: The aim of the current study was to investigate the expression of vascular endothelial growth factor (VEGF) by neoplastic cells in patients with serous ovarian tumors. The correlation between neoangiogenesis and 72-kilodalton metalloproteinase (MMP2) immunostaining also was evaluated. METHODS: Fifty-eight patients with serous ovarian tumors who were treated at the Institute of Gynecology and Obstetrics of Ancona University (Ancona, Italy) were used as the study population; 10 women had serous cystoadenoma, 16 women had a serous borderline tumor, and 32 women had invasive cystoadenocarcinoma. Expression of VEGF and MMP2 was evaluated immunohistochemically by polyclonal antibody anti-VEGF (dilution, 1:100) and affinity purified, rabbit anti-MMP2, formalin fixed, paraffin embedded tissue. Positive staining was expressed as a percentage of positive cells per 10(3) counted neoplastic cells. RESULTS: Compared with cystoadenomas and borderline tumors, the tessutal VEGF immunostaining was significantly higher in cystoadenocarcinomas, with the highest values detected in architectural International Federation of Gynecology and Obstetrics Grade 3 neoplasms (P2 < 0.001). A direct relation was observed between VEGF and MMP2 immunostaining (correlation coefficient, 0.44; P2 = 0.013). A relation was found between VEGF expression and disease free survival as evaluated by Cox hazards analysis (P2 = 0.03). CONCLUSIONS: Neoangiogenesis detected by VEGF immunostaining appears to be a promising indicator of aggressiveness in serous ovarian tumors. In cystoadenocarcinomas, VEGF expression appears to be related to MMP2 index.

Adult↗
PubMed1999

Cisplatin-based polychemotherapy reduces the natural cytotoxicity of peripheral blood mononuclear cells in patients with advanced ovarian carcinoma and their in vitro responsiveness to interleukin-12 incubation.

BACKGROUND: The aim of the current study was to evaluate the in vitro effect of IL-12 on the natural cytotoxicity of peripheral blood mononuclear cells (PBMCs) obtained from patients who underwent adjuvant-based cisplatin polychemotherapy for advanced ovarian carcinoma. The authors also investigated amifostine, a cytoprotective agent that appears to protect against chemotherapy damage to healthy tissues, to determine its effects on natural immune function. METHODS: Twenty-one women with advanced ovarian serous cystoadenocarcinoma who underwent adjuvant cisplatin-based polychemotherapy were included in the study, and 20 normal volunteer women matched for age served as controls. Six of the 21 women who underwent polychemotherapy received 1:3 amifostine pretreatment. Blood samples were obtained immediately before the first cycle of cisplatin-based polychemotherapy and within 24 hours after the completion of polychemotherapy infusion to evaluate the natural cytotoxic activity of PBMCs against the K562 cell line and the in vitro responsiveness of cytotoxic cells to interleukin-12 (IL-12). RESULTS: The in vivo administration of cisplatin-based polychemotherapy significantly reduced the natural killer cytotoxicity of PBMCs toward undetectable levels (2.2+/-3.1 vs. 9.2+/-7.0 lytic units, respectively, after and before cisplatin; P < 0.01), and the in vitro exposure to IL-12 did not increase the cytolytic activity of PBMCs (1.9+/-2.1 lytic units). PBMCs from the 6 patients who received random amifostine pretreatment were shown to have retained natural killer cytotoxicity after in vivo administration of cisplatin polychemotherapy (9.7+/-6.7 vs. 9.6+/-6.0 lytic units, respectively, after and before cisplatin; P = 0.9), and the incubation with IL-12 increased cytotoxic activity (13.4+/-6.9 lytic units) toward the levels observed in PBMCs of controls (14.0+/-4.6 lytic units). CONCLUSIONS: These data suggest that cisplatin-based polychemotherapy reduces the natural cytotoxicity of PBMCs in patients with advanced ovarian carcinoma as well as their in vitro responsiveness to IL-12 incubation. Amifostine demonstrated a protective effect on natural killer cell cytotoxicity and responsiveness to IL-12 in this small cohort of patients.

Amifostine↗
PubMed1999

Vascular endothelial growth factor expression as a prognostic index in serous ovarian cystoadenocarcinomas: relationship with MIB1 immunostaining.

OBJECTIVE: The aim of our study was to investigate the expression of vascular endothelial growth factor (VEGF) by neoplastic cells in serous ovarian cystoadenocarcinomas; the correlation between this marker of angiogenesis, histopathologic parameters, disease-free survival, and MIB1 immunostaining was also evaluated. MATERIALS AND METHODS: Thirty-two patients with serous ovarian cystoadenocarcinoma, treated at the Institute of Gynecology and Obstetrics, Ancona University (Italy), were used as study population; 10 women with serous cystoadenoma were also analyzed. The expression of VEGF was immunohistochemically evaluated by polyclonal antibody anti-VEGF (Santa Cruz, CA, dilution 1:100) on formalin-fixed paraffin-embedded tissue. RESULTS: Compared to cystoadenomas, the tissutal VEGF immunostaining was significantly higher in cystoadenocarcinomas, with the highest values in architectural grade 3 neoplasms (P < 0. 001). A direct relationship was observed between VEGF immunostaining and MIB1 index (r = 0.44, P = 0.013). A relationship was defined between VEGF expression and disease-free survival, evaluated by Cox hazards analysis (P < 0.001). CONCLUSIONS: Angiogenesis, evaluated by VEGF immunostaining, seems to be an interesting prognostic indicator in serous ovarian cystoadenocarcinoma, involved in neoplastic proliferation.

Adult↗
PubMed1999

In vivo amifostine (WR-2721) prevents chemotherapy-induced apoptosis of peripheral blood lymphocytes from cancer patients.

Aim of this work was to evaluate whether in vivo amifostine (WR-2721, ethanethiol, 2-[(3-aminopropyl)amino]-,dihydrogen phosphate (ester), Ethyol) pretreatment was able to prevent the apoptosis of peripheral blood lymphocytes (PBLs) induced by cytotoxic drugs. The study included 19 patients with advanced gynaecological cancers who received neoadjuvant polychemotherapy consisting of three cycles of cysplatin, adriamycin, and cyclophosphamide. Five patients received randomly amifostine pretreatment (910 mg/m2). PBLs apoptosis was measured through flow-cytometry using two different methods: a) DNA fragmentation of PBLs cultured in vitro for one hour; b) measurement of early apoptotic cells through Apostain uptake by fresh PBLs. The percentage of apoptotic PBLs was increased in all patients 24 hr after the first chemotherapy cycle (27.1 +/- 15.6 vs 6.3 +/- 6.2, p<.0001). A similar increase was observed in the following chemotherapy cycle. Amifostine pretreatment prevented the apoptosis of PBLs induced by chemotherapeutic drugs. Amifostine also prevented the reduction of lymphocyte number determined by chemotherapy. The results demonstrate that amifostine protects peripheral lymphocytes from the apoptotic damage induced by chemotherapy. This effect may explain the mechanism by which amifostine prevents the chemotherapy-associated reduction of leukocyte number.

Adult↗
PubMed1999

Role of zinc and alpha2 macroglobulin on thymic endocrine activity and on peripheral immune efficiency (natural killer activity and interleukin 2) in cervical carcinoma.

Decreased natural killer (NK) activity as well as interleukin 2 (IL-2) are risk factors for the progression of cervical carcinoma. NK activity and IL-2 may be thymus controlled. Plasma levels of active thymulin, a zinc-dependent thymic hormone (ZnFTS), are reduced in cancer because of the low peripheral zinc bioavailability. Zinc and thymulin are relevant for normal immune functions. Alpha2-macroglobulin is an inhibitor of matrix metalloproteases (MMPs) against invasive tumour proliferation. Because alpha2-macroglobulin has a binding affinity (Kd) for zinc that is higher than does thymulin, it may play a key role in immune efficiency in cancer. Plasma samples of 22 patients (age range 35-60 years) with locally advanced squamous cervical carcinoma and with FIGO stage Ib2-IIb were examined. They showed reduced active thymulin, decreased NK activity and IL-2 production, increased soluble IL-2 receptor (sIL-2R) and augmented alpha2-macroglobulin in the circulation, whereas plasma zinc levels were within the normal range for age. Significant positive correlations were found between zinc or active thymulin and alpha2-macroglobulin (r = 0.75, P < 0.01, r = 0.78, P < 0.01, respectively) in cancer patients. In vitro zinc increases IL-2 production from peripheral blood mononuclear cells (PBMCs) of cancer patients. These data suggest that an increase in alpha2-macroglobulin, which competes with thymulin for zinc binding, may be involved in causing a thymulin deficit with a consequent decrease of IL-2 and NK cytotoxicity. Thus, physiological zinc treatment in cervical carcinoma maybe restores impaired central and peripheral immune efficiency.

Adult↗
PubMed1998

The role of human papillomavirus DNAs in cervical carcinoma and risk of lymph node metastasis: association with 72-kilodalton metalloproteinase immunostaining.

BACKGROUND: The role of human papillomavirus (HPV) as a prognostic factor in cervical carcinoma is not understood completely and little is known regarding the intrinsic mechanisms involved in the metastatic process of HPV positive carcinoma. The authors evaluated HPV status with respect to clinical features in early stage cervical carcinoma, with special emphasis on lymph node spread. The authors also analyzed the relation between HPV, lymph node involvement, and 72-kilodalton (kDa) metalloproteinase immunostaining, an enzyme that cleaves Type IV collagen and may play a role in tumor metastasis. METHODS: Thirty-two patients with International Federation of Gynecology and Obstetrics Stage I and IIA squamous cell cervical carcinoma treated by primary radical surgery were reviewed. Histologic grade of differentiation, tumor size, fractional depth of invasion, and lymph node spread were evaluated with respect to HPV status and 72-kDa metalloproteinase immunostaining. HPV DNA was detected by polymerase chain reaction and the primers potentially recognized at least the following HPV subtypes: 6, 11, 16, 18, 31, 33, 34, 35, 42, 51, 56, and 58. Immunohistochemical staining was performed using the avidin-biotin complex technique. Affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. RESULTS: HPV DNA was detected in a total of 69% of cases, and HPV-16 was the most frequent type detected. HPV positive carcinomas showed a significantly higher rate of lymph node metastases than HPV negative carcinomas (45% vs. 10%; P = 0.03); similarly, 72-kDa metalloproteinase index was significantly higher (P = 0.001). CONCLUSIONS: These findings suggest a relation between HPV and risk of lymph node metastasis, which may be mediated by an increased production of 72-kDa metalloproteinase.

Amino Acid Sequence↗
PubMed1998

Decrease in peripheral blood polymorphonuclear leukocyte chemotactic index in endometriosis: role of prostaglandin E2 release.

OBJECTIVE: To investigate the effect of disease on peripheral blood polymorphonuclear leukocyte chemotactic index and natural killer cell cytotoxicity and to provide additional information concerning the cell-mediated immune function in endometriosis. METHODS: Chemotactic index of peripheral blood polymorphonuclear leukocytes, natural killer cell activity, and plasma estradiol (E2) and plasma prostaglandin (PG) E2 levels were evaluated in 46 women who underwent laparoscopy or laparotomy for pelvic pain, infertility, and/or benign adnexal masses. RESULTS: The 20 women (43%) with endometriosis showed a decrease in peripheral blood polymorphonuclear leukocyte chemotactic index, related to advanced disease stage (P < .001). A significant inverse correlation was observed between plasma PGE2 levels and chemotactic index in stage III and IV endometriosis (r = -.73, P = .004). Similarly, natural cytotoxicity was decreased significantly with respect to the stage of endometriosis (P = .004) and related inversely to plasma PGE2 levels (r = -.74, P = .003). A direct relationship was observed between PGE2 and plasma E2 levels (r = .59, P = .006). CONCLUSION: Advanced endometriosis is associated with decreased peripheral blood polymorphonuclear leukocyte chemotactic index and natural killer cytotoxicity, which may be related to plasma PGE2 and E2 levels.

Adult↗
PubMed1998

Combined ultrasonographically guided drainage and laparoscopic excision of large endometriomas: a pilot study.

We report a prospective pilot study which evaluated the feasibility of combined ultrasonographically guided drainage and laparoscopic excision after pre-operative administration of a gonadotrophin-releasing hormone analogue for 3 months in the management of ovarian endometriotic cysts >5 cm. Ten patients with an ultrasonographic diagnosis of large unilateral or bilateral ovarian endometriotic cysts received an intramuscular injection of leuprorelinum acetate 3.75 every 4 weeks for 12 weeks. After 4 weeks of medical treatment, the endometrioma was carefully drained transabdominally under ultrasonographic control. Within 8 weeks since the last injection, the patients were submitted to a second ultrasonography, and laparoscopy-guided stripping of the endometrioma was performed. A videotape review was undertaken to evaluate duration and complexity of the different phases of surgery. Stripping of endometriomas with preservation of residual ovarian parenchymas was obtained in all cases; adhesiolysis was complete in 6 cases. There were neither intra-operative complications nor conversions in laparotomy. In conclusion, gonadotrophin-releasing hormone analogue and cyst drainage seem to permit an easy laparoscopic approach of large endometriomas; the findings of our pilot phase seem to justify a randomized trial to better define the effectiveness of this approach with respect to standard procedures.

Adult↗
PubMed1997

MIB 1 immunostaining in cervical carcinoma of young patients.

OBJECTIVE: In the present study, we assessed whether biologic characteristics of tumors in young patients differ from those observed in older patients with the same clinical and histologic characteristics, but ranging in age from 50 to 70 years. The hypothesis to be verified was whether cervical carcinoma in young patients presented an increased proliferative activity which might explain more aggressive behavior. MATERIALS AND METHODS: Locally advanced cervical carcinoma tumor samples were obtained from our series of patients, maximum age 40 years, and immunohistochemically evaluated by monoclonal MIB 1 antibody (Immunotech, Marseille Cedex, France) on microwave-oven-processed Formalin-fixed paraffin-embedded tissue. Positive staining was expressed as a percentage of positive cells per 10(3) counted neoplastic cells for each case. For each young patient, a control was selected among patients aged >/=50 years (range 50-70) matched for stage, tumor size, histologic type and grading, and lymphvascular invasion. RESULTS: Fourteen of 73 patients (19.2%) with stage I and IIa cervical carcinoma who underwent primary radical surgery at our Institute between 1986 and 1994 were aged </=40 years. The MIB 1 index was significantly higher in young patients with respect to the older group (mean +/- standard deviation, 61.6 +/- 16.3% and 45.2 +/- 12.2%, with P = 0.006). CONCLUSIONS: Although any conclusions from this study need to be tempered because of the small number of patients involved, locally advanced cervical carcinomas present in young patients showed a more aggressive biologic behavior, expressed by a higher cell proliferation index.

Adult↗
PubMed1997

Longitudinal measurement of amniotic fluid index in term pregnancies and its association with intrapartum fetal distress.

OBJECTIVE: The aim of the present study was to evaluate the dynamic changes in serially obtained amniotic fluid index values and to determine any association with intrapartum fetal distress in a term population. MATERIALS AND METHODS: All patients, > or = 40 weeks of gestational age, evaluated at the Institute of Obstetrics and Gynecology, 'G. Salesi' Hospital, University of Ancona, between January 1, 1994, and December 31, 1995, participated in this longitudinal study. Women with an amniotic fluid index of > 50 mm, who also demonstrated a reactive nonstress test, underwent semiweekly amniotic fluid assessment until spontaneous labor. After 42 gestational weeks, the patients underwent an elective induction of labor. All patients were managed with continuous electronic fetal heart rate monitoring throughout labor. The incidence of intrapartum fetal distress, and meconium staining of amniotic fluid were evaluated with respect to the amniotic fluid index. RESULTS: Of the 117 patients that were evaluated by ultrasound, 83 women had multiple amniotic fluid index measurements and were enrolled in the study. A serial decrease in amniotic fluid index was documented in 54 women; the mean decrease per week was 20.7 +/- 15.4%. An increase in amniotic fluid index was noted in 17, while 11 women showed no change in amniotic fluid index over time. The 14 patients who underwent cesarean section for fetal distress had a significantly lower amniotic fluid index (p < 0.001) at the last sonographic examination than the normal outcome group. Significant differences were also observed for a serial decrease in the amniotic fluid index within a week (p < 0.001). The sensitivity and specificity of the 30% serial decrease in the amniotic fluid index cutoff point, with respect to intrapartum fetal distress were 86 and 93%, respectively. CONCLUSION: Longitudinal measurement of the amniotic fluid index seems to be an effective method in predicting intrapartum fetal distress in a term population.

Amniotic Fluid↗
PubMed1997

Prophylactic transabdominal amnioinfusion in oligohydramnios for preterm premature rupture of membranes: increase of amniotic fluid index during latency period.

OBJECTIVE: This study was designed to: (i) evaluate the effect of amnioinfusion on the latency period in patients with oligohydramnios for preterm premature rupture of membranes, and (ii) to investigate the relationship between changes in the amniotic fluid index and fetal heart rate short-term variability by computerized Hewlett-Packard cardiotocography, longitudinally estimated before and after prophylactic amnioinfusion. MATERIALS AND METHODS: All singleton pregnancies with prolonged premature rupture of membranes after 25 weeks of gestation and seen at the Institute of Obstetrics and Gynecology, University of Ancona (Italy), between January 1994 and June 1995 were included in the study. Transabdominal amnioinfusion with 150-350 ml warmed normal saline (25-50 ml/min) was performed at weekly intervals. Amniotic fluid volume was assessed ultrasonographically by means of the four-quadrant technique on a weekly basis before and after each amnioinfusion, as well as the short-term variability by a Hewlett-Packard computerized cardiotocographic system. RESULTS: 18 women were enrolled and underwent prophylactic transabdominal amnioinfusion at weekly intervals until delivery. Eighteen controls, who did not undergo prophylactic amnioinfusion, were recruited from our 1992-1993 series and included in the study. The median interval between premature rupture of membranes and delivery was 3.0 weeks (range 1-8 weeks), with an average delivery age of 33.0 weeks (range 27-36 weeks). The latency period was significantly longer in patients who underwent prophylactic amnioinfusion (mean +/- SD, 4.1 +/- 1.7 weeks) than in controls(1.7 +/- 1.0 weeks; p < 0.001). An increase in both the weekly amniotic fluid index (linear regression analysis r = 0.8, p = 0.03) and the weekly short-term variability (linear regression analysis r = 0.82, p = 0.02) was observed among patients who underwent prophylactic amnioinfusion. A direct relationship was observed between the amniotic fluid index and short-term variability (linear regression analysis r = 0.54, p = 0.04). The mean values of fetal movements recorded by computerized tomography during the 20 min of observation significantly increased after amnioinfusion in comparison with those before it (2.6 +/- 0.9 and 0.9 +/- 0.7 respectively; p = 0.001). CONCLUSION: The present study has shown a positive effect of prophylactic transabdominal amnioinfusion on the latency period in patients with preterm premature rupture of membranes and oligohydramnios. Among the patients who underwent amnioinfusion, an interesting improvement in fetal heart rate short-term variability was associated with the progressive increase in amniotic fluid volume, as an expression of fetal well-being.

Abdomen↗
PubMed1996

The 72-kDa metalloproteinase immunostaining in cervical carcinoma: relationship with lymph nodal involvement.

OBJECTIVE: In the present study we detected 72-kDa metalloproteinase expression in our series of early stage cervical carcinomas and analyzed the relationship between 72-kDa metalloproteinase staining and risk of nodal involvement with the goal of identifying a parameter useful in predicting the metastatic potential of lesions. MATERIALS AND METHODS: The medical records of 34 patients with FIGO stage I squamous cell cervical carcinoma who had undergone primary radical surgery with systematic pelvic and para-aortic lymphadenectomy (Piver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, between January 1988 and January 1993 were recruited from our series of 57 consecutive cases and reviewed. Any characteristic that could be relevant for prognosis was recorded in all of the cases: histologic grade of differentiation, tumor size, lymphatic spread, and adjuvant radiotherapy. Immunohistochemical staining was performed on serial sections of tumors using the avidin-biotin complex technique (Vector Laboratories, Burlingame, CA). The affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. Positive staining was expressed as a percentage of positive cells per 10(3) counted neoplastic cells (the 72-kDa metalloproteinase index). RESULTS: The tissue 72-kDa metalloproteinase immunoreactivity was diffusely expressed in all cervical carcinomas (ranging from 8.6 to 51.9%, with a median of 17.8%) and showed a significant relationship with respect to lymphatic spread. In the presence of lymph nodal involvement, the 72-kDa metalloproteinase index was significantly higher than in the absence of nodal metastasis (32.9 +/- 12.2% versus 18.1 +/- 9.0%, means +/- standard deviations with P = 0.001); a significant relationship was also observed between the 72-kDa metalloproteinase index and the number of positive nodes (r = 0.8, with P = 0.01). No significant relationship was defined with respect to the other prognostic parameters. The Cox proportional hazard analysis showed a significant relationship between the 72-kDa metalloproteinase index and disease-free survival (P < 0.0001) that was independent of tumor size, nodal involvement, and lymphvascular space invasion. CONCLUSIONS: Although the small numbers do not allow any definitive conclusion, a significant relationship between the 72-kDa metalloproteinase index and the risk of lymphatic spread is defined in early stage cervical carcinoma. The 72-kDa metalloproteinase immunostaining seems to have a prognostic value, suggesting the possibility of an association between neoplastic aggressiveness and 72-kDa metalloproteinase expression.

Adult↗
PubMed1996

Proliferating cell nuclear antigen in endometrial carcinoma: pretreatment identification of high-risk patients.

OBJECTIVE: The aim of our study was to retrospectively examine the proliferating cell nuclear antigen (PCNA) immunoreactivity of tumor cells in curettage specimens containing endometrioid adenocarcinoma and obtained immediately before definitive surgical staging. This PCNA index was compared with the one subsequently derived from surgical specimens and assessed as a function of histologic grade, depth of myometrial invasion, neoplastic nodal involvement, cervical spread, and progression-free survival in order to determine a new prognostic parameter valuable at the time of diagnosis. MATERIALS AND METHODS: A population of 79 patients with locally advanced (stage I and II) endometrioid carcinoma, who underwent both the preliminary diagnostic curettage and the subsequent definitive surgical management, selected from January 1986 to June 1993 at the Department of Gynecology and Obstetrics, Ancona University, was retrospectively recruited from our series of 99 endometrial carcinomas. The archival paraffin blocks from the curettage and uterine specimens were identified and assessed for histologic reexamination and PCNA immunostaining [PC10 monoclonal antibody (Dako, Denmark)]. RESULTS: After a median follow-up of 47 months, recurrences were detected in 7 cases, and the Kaplan-Meier disease-free survival curve estimated for the entire study group was 91%. The median PCNA index of the curettage specimens presented a good overlap with the PCNA immunostaining in corresponding uterine samples with a correlation coefficient of 0.4 (P=0.02). A PCNA index >/=30% in curettage specimen was predictive of deep myometrial invasion; of 35 patients with PCNA index > or = 30%, 29 (83%) had myometrial invasion > or = 50%. No significant relationship was observed with neoplastic cervical spread, and histologic differentiation. By Cox hazard analysis, the PCNA index evaluated on curettage specimens was significantly related to disease-free survival, with significant disease-free survival advantages for patients with PCNA <30% (P<0.001). CONCLUSION: Our findings suggest that the PCNA immunostaining has proved to be considerably promising for the risk assessment in locally advanced endometrial carcinoma. The PCNA index is an objective and reproducible parameter accruably valuable also before starting the treatment; in presence of a high PCNA index, the patients should be referred to gynecologic oncologists for appropriate management.

Adenocarcinoma↗
PubMed1996

Recurrence patterns in locally advanced cervical carcinoma: role of nodal status and 72-kDa metalloproteinase index.

OBJECTIVE: The aim of the study was to analyze the relationship between lymph nodal involvement and regional and/or distant recurrences in locally advanced squamous cervical carcinomas, and also evaluate tumor 72-kDa metalloproteinase, as a biologic parameter useful for understanding the mechanisms of disease relapse and prognosis. In particular, 72-kDa metalloproteinase is an enzyme that specifically cleaves type IV collagen and seems to play a critical role in tumor invasion and metastatic dissemination. METHODS: The medical records of 62 patients with FIGO (International Federation of Gynecology and Obstetrics) stage Ib and IIa squamous cervical carcinoma who underwent primary radical surgery with systematic pelvic and paraaortic lymphadenectomy and then were routinely followed were recruited from our series of 76 consecutive cases and reviewed. Fifty-four patients with complete clinicopathologic information were considered eligible for the study. All recurrences were defined as histologically and/or cytologically documented disease, following a minimum 3-month disease-free interval. Sites of recurrences were classified as distant, or regional to the pelvis. Immunostaining with 72-kDa metalloproteinase was performed on serial sections of tumors using avidin-biotin complex technique. Affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. Positive staining was expressed as a percentage of positive cells per 10(3) counted neoplastic cells (72-kDa metalloproteinase index). RESULTS: After a median follow-up of 38 months (range 9-71 months), 11 patients recurred with a 20% overall incidence. Seven patients (64%) recurred regionally, with side-wall infiltration in 2 cases, and 4 patients (36%) recurred distantly. By Cox hazard multivariate analysis, lymph nodal status was significantly related to disease-free survival (P = 0.01); in particular, all the patients with side-wall or distant recurrences had lymph nodal involvement. A significant relationship was also observed between tumor 72-kDA metalloproteinase immunostaining and disease-free survival (P = 0.02). The 72-kDA metalloproteinase index was significantly higher in patients who recurred than in patients with disease-free follow-up (P < 0.001); in particular, the highest values were detected in patients who recurred distantly. A relationship between 72-kDa metalloproteinase staining and nodal status was observed (P < 0.001). CONCLUSIONS: In conclusion, nodal status and the 72-kDa metalloproteinase index were two independent prognostic parameters, significantly related to recurrence risk and pattern of recurrence in locally advanced cervical carcinoma. Although they are independent prognostic parameters, a relationship between nodal involvement and 72-kDa metalloproteinase was observed. A model of tumor recurrence in which intrinsic tumor factors exert their negative influence directly or by contributing to the development of nodal metastases seems possible.

Animals↗
PubMed1996

Microinvasive cervical carcinoma and cervical intraepithelial neoplasia: biologic significance and clinical implications of 72-kDa metalloproteinase immunostaining.

OBJECTIVE: The immunohistochemical expression of 72-kDa metalloproteinase was evaluated in cervical intraepithelial neoplasia (CIN) and microinvasive carcinoma, with the aim to define a relationship between 72-kDa metalloproteinase expression and neoplastic invasiveness, useful to identify subsets of intraepithelial lesions with higher risk of progression. MATERIALS AND METHODS: Cervical bioptic samples were obtained consecutively from 54 women who attended our Colposcopic Service from January 1993 to July 1993 because of abnormal pap smear, suspicious for cervical dysplasia and/or human papillomavirus infection. After written consent, 29 women with CIN were included in the study. All women with CIN 3 lesion underwent conization; in 21 women with mild or moderate cervical dysplasia, we did not perform any medical or physical treatment but followed them longitudinally at close interval. After 12 months, the clinical evolution was classified as spontaneous remission, persistence, or progression depending on the absence or presence of lesion and/or HPV infection in colposcopy, histology, and polymerase chain reaction findings. In the study we also included surgical specimens from 10 women with microinvasive squamous carcinoma who underwent primary radical surgery. Seventy-two kilodalton metalloproteinase positivity was immunohistochemically stained on serial sections by using the avidin-biotin complex technique (Vector Laboratories, Burlingame, CA) and expressed as percentage of cells per 10(3) counted neoplastic cells. RESULTS: Cytoplasmatic positive 72-kDa metalloproteinase immunostaining was significantly higher in microinvasive cervical carcinomas than in CIN lesion (Student's t test; P < 0.001). Considering only cervical intraepithelial neoplasias, a significant increase in 72-kDa metalloproteinase immunostaining was observed with CIN degree increasing (one-way analysis of variance; P = 0.002). No correlation was found between 72-kDa metalloproteinase immunostaining and HPV infection and lesion size defined by quadrants of the cervix involved with colposcopically evident dysplasia. By analyzing 72-kDa metalloproteinase positivity, regressive dysplasia showed low values of 72-kDa metalloproteinase immunostaining (median 1.2%, range 0.5-1.8%), while persistent (median 2.6%, range 1.9-3.6%) and progressive lesions (median 4.6%, range 2.3-6.9%) presented a significantly higher positivity (one-way analysis of variance; P < 0.001). DISCUSSION: In conclusion, the 72-kDa metalloproteinase expression is related to invasive potential with a significant increase in staining positivity in microinvasive carcinomas; 72-kDa metalloproteinase is detectable in cervical dysplasia, and it is related to the severity of cellular atypia. A clinical implication of 72-kDa metalloproteinase immunostaining seems to be indicated, by analyzing the differences in 72-kDa metalloproteinase positivity rates between regressive and persistent or progressive disease.

Adult↗
PubMed1996

Natural cytotoxicity and GnRH agonist administration in advanced endometriosis: positive modulation on natural killer activity.

OBJECTIVE: To investigate the effects of pharmacologic suppression of ovarian function on the immune system, with respect to the clinical outcome of endometriosis and the possibility of an immunoendocrine combined treatment. METHODS: After informed consent, 25 of 37 patients with revised American Fertility Society stage III and IV endometriosis who underwent postoperative medical treatment were selected and enrolled for this immunoendocrine longitudinal study. Medical treatment consisted of tryptorelinum depot injection, 3.75 mg/month for 24 weeks. Blood samples were collected before the first injection in the early follicular phase, day 2-3 of the cycle, and during medical treatment (every 4 weeks) and follow-up (every 6 months). At the end of the study, we had ten blood samples per patient to evaluate the cytotoxic activity, the number of natural killer cells, and the serum levels of estradiol. Natural killer activity was determined against the K562 cell line by target cell retention of the fluorescent dye carboxyfluorescein diacetate. RESULTS: A positive immunomodulating effect was observed during GnRH agonist administration. In particular, a significant progressive increase in natural killer cell activity was defined within the first 12 weeks of medical treatment; after three injections, we observed the highest values of cytotoxicity, with a median of 7.1 lytic units (range 0.3-14.0; P = .02). Natural cytotoxicity then decreased toward a plateau, which persisted during therapy completation and follow-up, with slight fluctuations. In patients who had recurrence, the values of natural killer cell activity were constantly lower than those in patients with disease-free follow-up, particularly within the first 12 weeks of medical treatment.

Adult↗