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Biomedical subjects

G Baiocchi

Publications and source records attributed to G Baiocchi.

At least 19 recordsLinked to original sources

Systematic pelvic and paraaortic lymphadenectomy at second-look laparotomy for ovarian cancer.

A retrospective review of the medical records of all ovarian cancer patients admitted to our institution from January 1974 to December 1993 was performed. A total of 58 consecutive patients who underwent systematic pelvic and paraaortic lymphadenectomy during second-look surgery was found. Node metastases were found in 15 of 58 patients (25.8%). No significant correlation was found between the variables of disease (e.g., stage of the disease at diagnosis, histology, grade, residual tumor after the first cytoreductive surgery, and the type of chemotherapy administered) and node status at second-look. Node metastases were found in 8 of 45 (17.7%) patients with absence of intraperitoneal disease, compared with 7 of 11 (63.6%) patients with intraabdominal residual disease (P < 0.02). There was no difference in 5-year survival for patients with absence of residual tumor in the peritoneal cavity as well as in the retroperitoneum (5-year survival 80%) and for patients with retroperitoneal disease only (5-year survival 77%). On the contrary, a highly significant difference in survival (P < 0.001) was observed between these two groups of patients and those who had intraabdominal residual tumor. Twelve of 45 (26.6%) patients have recurred. FIGO stage, grade, and residual disease after primary surgery were determinant in predicting recurrence. Notably, no relation emerged between relapse rate and the node status at second-look.

Adult↗

Pure Leydig cell tumour (hilus cell) of the ovary: a rare cause of virilization after menopause.

A 58-year-old postmenopausal woman with high plasma testosterone levels and virilization, as demonstrated by hirsutism and alopecia, is presented. Urinary 17-ketosteroids and 17-hydroxycorticosteroids as well as the computed axial tomography scan of the adrenal glands were normal. Although no pelvic mass was detected by sonography or pelvic examination, the patient was found to have small pure Leydig cell tumour of the left ovary. Following total abdominal hysterectomy and bilateral salpingo-oophorectomy, the patient had regression of the hirsutism, and the plasma testosterone dropped to normal level.

17-alpha-Hydroxyprogesterone↗

[Endometrial carcinoma: an increasing neoplasm. Screening and early diagnosis: proposal for a protocol].

Endometrial cancer is the most common cancer of the genital tract and it represents 10% of all cancers diagnosed in women. A protocol for screening and early diagnosis of this tumor has been designed by the authors. All asymptomatic women with risk factors undergo transvaginal sonography. The value of endometrial thickness suggests the need for endometrial sampling. On the contrary, such a procedure is always combined with transvaginal sonography in case of women with atypical genital bleeding. The aim of the protocol is to verify the efficacy of transvaginal sonography and endometrial sampling as combined procedures for screening and early diagnosis of endometrial cancer.

Aged↗

Fallopian tube cancer: incidence and role of lymphatic spread.

Lymphatic spread pattern in 17 cases of adenocarcinoma of fallopian tube is reported. Median age of the patients was 48 years. All patients underwent surgical staging including total abdominal hysterectomy, bilateral salpingo-oopherectomy omentectomy, and appendectomy. Systematic pelvic and paraaortic lymphadenectomy was feasible in 15 cases. Majority of the patients (11 of 17 cases, 64%) had advanced disease and showed serous adenocarcinoma (83%). Lymph nodes were involved in 10 of 17 cases (59%). Node metastases rate increased significantly (P < 0.01) with intraperitoneal stage of disease and with grading. Interestingly, positive nodes were also found in 2 cases (33%) of 6 patients with disease still limited to fallopian tube. Overall, patients with negative nodes had a median survival of 76 months, compared with only 33 months if node metastases were found. In conclusion, combined pelvic and para-aortic lymphadenectomy seems to be necessary for staging and perhaps for prognosis of this disease.

Adenocarcinoma↗

Systematic pelvic and paraaortic lymphadenectomy for advanced ovarian cancer: prognostic significance of node metastases.

A retrospective study of 488 patients with untreated advanced ovarian cancer is presented. Systematic pelvic and paraaortic lymphadenectomy was performed in 248 cases (50.8%). Selective sampling and node biopsy was performed in 33 (6.7%) and 47 (9.6%) patients, respectively. Node metastases were found in 194 of 328 patients (59.1%). The incidence of metastatic nodes significantly increased with more advanced stages, with serous histology, and with a greater amount of residual tumor. Node status appeared to be related to pathology findings at second-look. A complete pathologic response was documented in 26 of 31 (83.8%) patients with negative nodes and in 38 of 59 (64.6%) with positive nodes at first surgery. Patients with negative nodes survived significantly longer (5-year survival, 46%; median, 60 months) than those who had node metastases (5-year survival, 25%; median, 36 months). Using multivariate analysis, lymph node status, together with the stage of disease and residual tumor, still had a significant impact on 5-year survival. Moreover, among patients with optimal cytoreduction, 5-year survival was 46% (median, 56 months) and 30% (median, 41 months) for patients who did and did not undergo lymphadenectomy, respectively (P = 0.05). Likewise, when suboptimal cytoreduction was considered, a median 5-year survival of 24 months was obtained in patients who underwent lymphadenectomy compared with 14 months in patients who did not (P < 0.005).

Adult↗

Very high-dose chemotherapy with autologous peripheral stem cell support in advanced ovarian cancer.

20 patients with stage III-IV ovarian cancer were submitted to induction chemotherapy (ICT) (40 mg/m2 cisplatin, days 1-4; 1.5 g/m2 cyclophosphamide, day 4; every 4 weeks for 2 cycles) followed by intensified CT (100 mg/m2 cisplatin, day 1; 650 mg/m2 etoposide, day 2; 1.8 g/m2 carboplatin by 24 h infusion, day 3). Haematological support consisted of autologous peripheral stem cells (APSC) and bone marrow (ABM) transplant (T) in 16 and 4 patients, respectively. All patients were evaluable for toxicity and 19 for pathological response (PR), one patient dying of systemic mycosis after ABMT. Severe (grade 3-4) non-haematological toxic effects were gastrointestinal (100%), neurological (10%) and hepatic (10%). PR was observed in 84% of patients (complete response 37%, partial response with microscopic residual disease 26%, partial response with macroscopic residual disease 21%). Five year overall survival was 60% and progression-free survival was 51% with 9 patients still disease-free (DFS). APSCT significantly reduced the duration of aplasia compared with ABMT, and toxicity was acceptable in those patients undergoing APSCT. The prolonged DFS in patients showing PCR suggests that this new approach may have a therapeutic impact.

Adenocarcinoma↗

Autologous stem cell transplantation: sequential production of hematopoietic cytokines underlying granulocyte recovery.

We investigated the serum concentrations of a variety of cytokines [granulocyte-macrophage-colony-stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), interleukin (IL) 1 alpha, IL-3, IL-6, IL-8, erythropoietin, tumor necrosis factor alpha, gamma-interferon in 10 patients with advanced ovarian cancer undergoing autologous peripheral blood stem cell (PBSC) harvesting followed by treatment with high-dose cisplatin, etoposide, and carboplatin and PBSC transplantation (chemotherapy was administered on days 1 through 3, PBSCT on day 6). Preliminary observations on cytokine serum levels were performed for 4 patients; on this basis, the kinetics of cytokines was then investigated in greater detail at closely sequential times in 6 further patients. We observed a consistent pattern of sequential GM-CSF, G-CSF, and IL-8 release after chemotherapy/PBSCT in all 10 cases, including the 6 patients monitored in detail: (a) at days 5-10 a GM-CSF peak; (b) at days 12-14 a pronounced release of both G-CSF and IL-8, which always preceded granulocyte recovery by approximately 7 days. At days 17-23, a second GM-CSF peak was monitored in 5 of the 6 patients analyzed in detail, as well as in the other 4 cases. Particularly relevant are the observations that: (a) the peak of G-CSF serum concentration and neutrophil number in the recovery phase are strikingly and directly correlated, thus indicating a key role for G-CSF in granulocyte rescue; (b) the time courses of G-CSF and IL-8 levels are strictly parallel, thereby suggesting a coordinate stimulus for production of granulocytes, mediated by G-CSF, and their activation/migration capacity, mediated by IL-8. Results were essentially negative for IL-3, tumor necrosis factor alpha, and gamma-interferon concentrations (except in one case for each cytokine). An early peak of IL-1 alpha was observed in all 3 analyzed patients, while an IL-6 peak was monitored at days 13-15 in all 4 patients analyzed in detail. The present results indicate a sequential coordinate pattern of cytokine release after ablative therapy and PBSCT and shed light on the mechanisms mediating the recovery of granulocytes, and more generally of hematopoiesis, after stem cell transplantation. Furthermore, these studies may contribute to the design of improved protocols for cytokine administration following myelosuppressive anticancer therapy, as well as to the prediction of granulocytic response.

Adult↗

Radical hysterectomy: a randomized study comparing two techniques for resection of the cardinal ligament.

To compare two different surgical techniques for the resection of the cardinal ligaments during radical operation for cervical cancer, 84 patients with locally advanced cervical cancer (FIGO stages IB-IIA > or = 4 cm, IIB-III) primarily treated with chemotherapy and then eligible for radical surgery underwent radical hysterectomy. Lateral parametria were resected by using the Meigs technique or a modified Magara technique. The procedure to be performed on the right hand side was randomly chosen, consequently the left cardinal ligament was resected with the other technique. Evaluation of the first 35 cases showed that the median size of the parametria resected with the modified Magara technique (52 mm) was significantly greater than that removed with the Meigs technique (34 mm) (P < 0.05). Therefore hemoclips were routinely adopted in the following 49 cases. In 11% of cases hemoclips could not be used due to a deep and narrow pelvis or varicosities of the hypogastric plexus, therefore clamps were necessary. Bleeding complicating parametrial dissection occurred independently of the adopted technique. Five-years DFS is 100, 80, and 52% for stage IB-IIA > 4 cm, IIB and III, respectively. The study showed that the modified Magara technique is feasible and safe and allows for a more radical resection of the parametrial tissue. Furthermore, this approach seems to improve the local control of disease.

Adenocarcinoma↗

Immunological reconstitution after high-dose chemotherapy and autologous blood stem cell transplantation for advanced ovarian cancer.

We evaluated the immunological reconstitution of patients who underwent high-dose chemotherapy and autologous blood stem cell transplantation (ABSCT) for advanced ovarian cancer. Sixty days after transplantation a complete reconstitution of lymphocytes and of the CD3, CD4, CD8, CD19, and CD16/56 subsets was observed in this series. A significant increase in the count of interleukin-2 receptor expressing lymphocyte (CD25) was found on day +60 after transplantation compared to that obtained at diagnosis and before transplantation. A significantly higher lymphokine-activated killer (LAK) precursor activity was seen on day +60 compared to the values obtained at diagnosis and before transplantation while natural killer activity did not show any significant variation. We conclude that ABSCT gives prompt and complete immunohaematopoietic reconstitution after high-dose treatment. Moreover, our data support the feasibility of interleukin-2/LAK therapy as consolidative therapy after ABSCT.

Antineoplastic Combined Chemotherapy Protocols↗

Expression of ras oncogene p21 protein in normal and neoplastic ovarian tissues: correlation with histopathologic features and receptors for estrogen, progesterone, and epidermal growth factor.

OBJECTIVE: The aim of the study was to investigate the biologic significance of p21 expression in normal and neoplastic ovarian tissues. STUDY DESIGN: Western blotting analysis of p21/ras oncoprotein was conducted in a group of 14 normal and cystic ovaries, six benign tumors, 42 primary ovarian cancers, and 15 omental metastases. RESULTS: Levels of p21 were similar in normal and cystic ovaries and in benign tumors, whereas they were significantly higher in malignant tumors than in control tissues (median 1.91, range 0.12 to 5.00 vs median 1.03, range 0.32 to 2.20; p = 0.023) and in omental metastases than in primary ovarian carcinomas (median 3.05, range 0.55 to 5.72 vs median 1.97, range 0.12 to 5.00; p = 0.14). We found no correlation between p21 expression and histopathologic or clinical characteristics. Estrogen receptor-positive and progesterone receptor-positive tumors expressed higher p21 levels than did estrogen receptor-negative and progesterone receptor-negative tumors (p < 0.05), but no correlation with epidermal growth factor receptor status was found. In the univariate analysis of survival p21 positivity showed a negative prognostic value. CONCLUSION: The enhancement of p21 protein is associated in the ovarian tissue with the malignant phenotype and the acquisition of metastatic potential.

Adult↗

Mitomycin C and 5-fluorouracil salvage chemotherapy in platinum-resistant ovarian carcinoma.

Twenty-four patients with progressing or recurrent ovarian carcinoma, all pretreated with cisplatin, were evaluated for response and toxicity to mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy. Eligible patients had histologically proven intra-abdominal disease (67% clinically measurable; 33% nonmeasurable), and 67% of them had progressed on prior platinum-based chemotherapy. WHO response criteria were adopted in patients with measurable disease while those with nonmeasurable lesions were considered as responding in case of nonevident disease and CA-125 values less than 35 U/dl for at least 6 months. All patients received at least 2 treatment courses (median 6, range 2-10), and 5 patients (21%) could be considered as responding: 4/8 (50%) with nonmeasurable and 1/16 (6%) with measurable disease. The overall median survival was 12 months, range 7-30+ (median follow-up: 29.5 months, range 28-30). Progression-free survival was significantly different in responders (15 months) versus nonresponders (3 months) (p = 0.0001). Toxicity was mainly represented by myelosuppression (grade I 29%; II 8% and III 4%). MMC and 5-FU did not show significant activity against large tumor burden, while a relatively good activity was detected in patients with minimal disease. The limited toxicity and possible schedule modifications have to be taken into account for further investigation on selected patients.

Adult↗

Significance of epidermal growth factor receptor in advanced ovarian cancer.

PURPOSE: The purpose of this study was to investigate the significance of epidermal growth factor receptor (EGF-R) expression in a group of advanced ovarian carcinomas. PATIENTS AND METHODS: The study was conducted on 72 previously untreated patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IV disease. The median follow-up was 24 months (range, 4 to 75 months). EGF-R was measured by a radioreceptorial assay. A cutoff of 1.5 fmol per milligram of protein was chosen to define EGF-R positivity. Medians and life tables obtained with the Kaplan and Meier method were analyzed by the log-rank test. The risk of progression was estimated by Cox's proportional hazards model. RESULTS: EGF-R was detected in 54% of primary tumors. When EGF-R was analyzed in different tissue specimens of the same tumor, consistent findings were noted in 88% (seven of eight) of cases. A lower concordance rate (nine of 15; 60%) was found between primary tumors and omental metastases, with a tendency toward higher EGF-R levels in the latter. The EGF-R expression did not significantly correlate with age, stage, grading, and residual tumor after primary surgery. In the univariate analysis, stage IV disease, postoperative residual tumor diameter greater than 2 cm, presence of ascites, and EGF-R positivity were found to be significantly associated with a greater risk of disease progression. In the multivariate analysis, only the postoperative residual tumor and the EGF-R expression remained significantly associated with a high risk of progression. CONCLUSION: Data reported here suggest that the presence of EGF-R in advanced ovarian tumor at the time of the primary surgery identifies a subset of patients with a particularly poor prognosis.

Analysis of Variance↗

Anatomical study of para-aortic and pelvic lymph nodes in gynecologic malignancies.

Between January 1986 and June 1990, systematic para-aortic and pelvic lymphadenectomy was performed in 208 women with untreated ovarian, endometrial, and cervical cancers. This study aimed to evaluate the median number of nodes collected from each pelvic and para-aortic group and to verify a new detailed nomenclature for the various lymph node groups. The para-aortic nodes were distinguished as paracaval, precaval, and retrocaval, depending on their relationship with the vena cava. Para-aortic, pre-aortic, and retro-aortic nodes were located close to the aorta. The nodes situated between the vena cava and aorta were designated intercavo-aortic. A median of 26 (range 15-48) para-aortic nodes were collected during ovarian or endometrial cancer operations. The lymphatic system of the pelvis was divided into six groups, depending on the relationship with the pelvic blood vessels. The pelvic nodes were distinguished as common, internal and external iliac, presacral, obturator, and parametrial. In cases of cervical cancer, the median number of pelvic nodes collected was 38 (range 20-88). Such anatomical study of the lymphatic system shows that a higher number of nodes than expected can be found in the retroperitoneum.

Aorta, Abdominal↗

Recombinant alpha-2b-interferon dynamic test as a potential tool in predicting disease status during second look in ovarian cancer. A preliminary report.

The circulating levels of a 90-kilodalton (KD) tumor-associated antigen were measured in the blood of 26 patients with ovarian cancer in clinical remission who received a short course of recombinant alpha-2b-interferon (rIFN-alpha-2b, 3 million U/m2/d intramuscularly for 3 days) before second-look procedures. The administration of rIFN-alpha-2b to 90-KD antigen-positive patients produced a slight increase of the marker. However, in patients without the marker but with evidence of disease, a remarkable increase above the cutoff level was observed. Less pronounced modifications of 90-KD antigen serum levels were found in patients with no disease at second look. Moreover, considering the 90-KD antigen mean percentage increase, the dynamic test with rIFN-alpha-2b was able to eliminate five of six false-negative results obtained with the 90-KD antigen basal assay alone. The sensitivity of the assay increased to 92% after IFN compared with 54% for the 90-KD antigen assay alone. An increase (greater than 100% above pretreatment titer) of 90-KD antigen levels during the test also was observed in four patients with no evidence of disease at second look. In two of these false-positive cases, recurrence of disease was observed 13 and 24 months later. At the time of this analysis, none of the patients with a negative second look and negative dynamic test had relapsed. These results suggest that the dynamic test with rIFN-alpha-2b might be a new tool to assess disease status in patients with ovarian cancer before second-look procedures.

Adult↗

Expression of the macrophage colony-stimulating factor and its receptor in gynecologic malignancies.

Recently, hematopoietic growth factors have been implicated in protean nonhematopoietic processes. In the current study, expression of macrophage colony-stimulating factor (M-CSF) and its receptor (the c-fms proto-oncogene) was investigated in 42 samples of gynecologic tissues. There were 15 samples of normal ovarian and uterine tissue or benign conditions of these organs; 11 samples of primary ovarian cancer tissue; seven samples of metastatic ovarian cancer tissue; and nine samples of primary endometrial cancer tissue. Steady state transcript levels were assessed by Northern Blot analysis. Macrophage colony-stimulating factor (M-CSF) expression was not observed in any of the specimens of benign abnormalities or of normal organs; c-fms expression was detected in two of 15 (13%) of these specimens, albeit at very low levels. In contrast, 14 (78%) of 18 ovarian tumor specimens, and five (55%) of nine endometrial tumor specimens expressed M-CSF. Similarly, 16 (89%) of 18 ovarian tumor specimens and six (67%) of nine endometrial tumor specimens expressed c-fms. Most positive malignant tissues (19 [86%] of 22) showed coexpression of M-CSF and c-fms. Of interest, M-CSF and c-fms mRNA were detected in tumor, but not in adjacent normal tissue. Furthermore, M-CSF and c-fms transcripts were produced by all metastatic tumors, including two cases in which the corresponding primary tumor from the same patient was negative. Because M-CSF mediates its effects by binding to its receptor, the increased levels of both these gene products in gynecologic malignancies suggest that an interaction between M-CSF and c-fms may participate in the development of ovarian and endometrial carcinomas and especially in progression to the metastatic state.

Blotting, Northern↗

Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival.

Between January 1986 and September 1988, 75 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stages IB-III) received three courses of neoadjuvant chemotherapy (NAC), including cisplatin, bleomycin, and methotrexate (PBM). Fifteen percent of patients achieved a complete response (CR) and 68% a partial response (PR). Pretreatment characteristics were analyzed for response to NAC. Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall. None of the biological parameters studied was related to chemoresponsiveness. Patients achieving CR or PR had a significantly improved 3-year survival rate compared with those who did not respond. After NAC, radical surgery was possible in all responding patients. The median number of lymph nodes removed was 60. A lower than expected incidence of lymph node metastases was detected. None of the clinical and pathologic features considered was significantly correlated with the lymph node status. Twelve of the 62 operated patients had disease recurrence. Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence. A 3-year, disease-free survival of 89%, 73%, and 43% for Stage IB-IIA, IIB, and III, respectively, was found. Among the operated patients these rates increased to 100%, 81%, and 66% for Stage IB-IIA, IIB, and III, respectively. A prospective randomized trial comparing NAC and surgery with radiotherapy alone is in progress.

Adenocarcinoma↗