Duloxetine and escitalopram for hot flushes: efficacy and compliance in breast cancer survivors.

Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) might be an effective treatment for hot flushes (HFs) in breast cancer survivors (BCSs). This study aims to compare the efficacy and tolerability of duloxetine (SNRI) versus escitalopram (SSRI) in reducing frequency and severity of HFs in BCSs and to assess the effect on depression. Thirty-four symptomatic BCSs with emotional impairment received randomly duloxetine 60 mg daily or escitalopram 20 mg daily for 12 weeks. Patients were asked to record in a diary HF frequency and severity at baseline and after 4 and 12 weeks of treatment. Depression was evaluated through validated questionnaires (Beck Depression Inventory and Montgomery Asberg Depression Rating Scale) at baseline and after 4 and 12 weeks of treatment. Both drugs showed a significant reduction of HF frequency and severity after 12 weeks of treatment with no significant difference between the two groups. A significant improvement in depression symptoms was observed at the end of the study period within both the groups, without difference between the two drugs. In conclusion, escitalopram and duloxetine are both effective treatment for the relief of HFs in BCSs, with similar beneficial effect. A significant improvement of depression was obtained with no major side effects.

Radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy: analysis of 49 cases from a single-centre and review of the literature.

The purpose of this study was to evaluate the reliability of image-guided 14-gauge needle core biopsy in the diagnosis of radial scar without associated atypical epithelial proliferation, by comparison with definitive histological diagnosis on surgical excision. The records of 8792 consecutive image-guided 14-gauge needle core biopsy of the breast performed from January 1996 to December 2009 were reviewed. Forty-nine cases of radial scar without associated atypical epithelial proliferation were identified and compared with definitive histological diagnosis on surgical excision. The definitive histological diagnosis on surgical excision confirmed the results of image-guided 14-gauge needle core biopsy in 36 of 49 cases (73.5%), in 9 cases (18.3%) radial scar was associated with atypical epithelial proliferation, while 4 cases out of 49 cases were upgraded to carcinoma (3 cases of ductal carcinoma in situ and one case of invasive lobular carcinoma), with an underestimation rate of 8.2%. A diagnosis of radial scar without associated atypical epithelial proliferation on image-guided 14-gauge needle core biopsy does not exclude a malignancy on surgical excision; consequently during the multidisciplinary discussion further assessment by surgical excision or vacuum-assisted excision, as recently reported, needs to be considered to obtain a definitive histological diagnosis.

Loco-regional recurrence in 2064 patients with breast cancer treated with mastectomy without adjuvant radiotherapy.

INTRODUCTION: We investigated the incidence of loco-regional recurrence in a sub-group of patients who underwent mastectomy without adjuvant radiotherapy to evaluate the effect of each specific clinical or pathological parameter that could be associated with a higher local relapse rate. PATIENTS AND METHODS: Two thousand and sixty-four patients were treated from January 1971 to December 2003 at the University of Florence. RESULTS: At the time of analysis 18.3% of patients (378/2064) had isolated loco-regional failures. Univariate analysis showed an association of borderline statistical significance with pathological tumour size. Elderly age at diagnosis had a low incidence of local recurrence but the results did not reach statistical significant. The number of positive axillary lymph node did not show any influence for local recurrence. CONCLUSION: In our series we noted a higher relapse rate only related to the pathological tumour size without any correlation with number of positive axillary nodes. Radiotherapy after mastectomy still remains controversial, but in our series the number of positive axillary lymph node did not seem enough to justify adjuvant treatment.

Ovarian cancer in the elderly: feasibility of surgery and chemotherapy in 89 geriatric patients.

Gynecological oncologists are faced with an increasing proportion of geriatric ovarian cancer patients. Comorbidities are frequently a matter of concern in this age group, and what is adequate treatment for such patients is still debated. The aims of this study were to analyze the feasibility of standard surgery and chemotherapy in a series of elderly ovarian cancer patients (>/=70 years) and to investigate the influence of age (70-75 vs >75 years) on survival. We retrospectively evaluated 89 elderly patients treated at our department between 1985 and 2005. Comorbidities, type of surgical procedure, complications, drugs and schedules of chemotherapy, number of cycles, toxicity, and clinical outcome were registered. Comorbidities were present in 71.9%. Only six patients were inoperable. Among the 83 patients who underwent surgery, 76.4% received adequate surgical treatment. Severe postoperative complications occurred in 16.8%, operative mortality was zero. A total of 801 cycles of chemotherapy were administered to 77 patients (median 10; range 1-38). Overall, G3-G4 toxicity was documented in 61.0%. The rates of dose reduction, treatment delay, and discontinuation were 13.0%, 20.7%, and 3.9%, respectively. Patients who received adequate surgery and those with residual disease <1 cm did significantly better than their counterparts (P= 0.04 and P < 0.001, respectively). No difference in survival according to age (70-75 vs >75 years) was found. Standard surgery and chemotherapy were feasible in elderly ovarian cancer patients. The type of surgery and the amount of residual disease, but not the age of the patients, significantly influenced the clinical outcome.

Expression and amplification of HER-2/neu oncogene in uterine carcinosarcomas: a marker for potential molecularly targeted treatment?

Surgery is the treatment of choice for uterine carcinosarcomas; nevertheless, the poor effect of chemotherapy and radiotherapy represents an insidious problem for patients with metastatic or unresectable disease, and indeed, new therapeutic approaches are clearly required to improve survival of uterine carcinosarcoma patients. The HER-2 oncogene, located on chromosome 17, encodes for a tyrosine kinase growth factor receptor. We analyzed HER-2/neu overexpression by immunohistochemistry in 28 uterine carcinosarcomas. HER-2/neu amplification with fluorescence in situ hybridization (FISH) was tested in positive cases. The expression of HER-2/neu was correlated with disease-free interval and survival (Kaplan-Meier estimates). We observed HER-2/neu overexpression in nine cases (32.1%) and HER-2/neu amplification in all the four HER-2/neu 3+ score positive cases tested by FISH. HER-2/neu expression was not correlated with clinical outcome. Patients with disease limited to the uterus (stages I-II) displayed a significantly better disease-free survival (P= 0.004) and actuarial survival (P= 0.01). Demonstration of HER-2/neu overexpression and amplification in uterine carcinosarcoma may represent the first rationale step for further investigations. Hence, the results of this analysis may support the challenge of a new therapeutic approach, which could test the role of anti-HER-2 (trastuzumab) in patients with advanced or metastatic uterine carcinosarcoma.

Radiofrequency bipolar coagulation for radical hysterectomy: technique, feasibility and complications.

This study describes the surgical technique and intra- and postoperative complications associated with the use of a radiofrequency bipolar coagulator in a series of 18 Piver type III-IV radical hysterectomies performed in cervical cancer patients. Preliminary vessel-by-vessel dissection of the lateral parametria was possible in 17 out of 18 (94%) cases, and a direct application of a radiofrequency bipolar coagulation instrument was performed to coagulate the posterior and anterior parametrial tissues in all cases. We were able to easily coagulate isolated vessels up to 5 mm of maximal diameter. In no case were clamps or hemoclips necessary to complete hemostasis. We did not observe any parametrial vessel damage or heat-related injury of the surrounding normal tissue. The median size of the parametria removed was 44 mm (range 31-58) and nodes were detected in 15 cases (83%). Median operative time and estimated blood loss for the whole procedure including systematic pelvic and aortic lymphadenectomy was 250 min (range 200-410) and 550 ml (range 400-2500), respectively. Median follow-up time was 9 months (range 5-13). No complications specifically related to the use of radiofrequency coagulation were found. In conclusion the radio-frequency coagulation with this instrument appears to be a safe technique that is particularly useful in reducing blood loss and operative time without affecting radicality in patients undergoing radical hysterectomy.

Systematic pelvic and aortic lymphadenectomy in elderly gynecologic oncologic patients.

BACKGROUND: Retroperitoneal lymph node dissection is a fundamental step in the surgical management of patients with pelvic gynecologic malignancies, but its applicability to geriatric patients is controversial. The objective of this study was to evaluate whether pelvic and aortic lymphadenectomy in elderly patients with gynecologic malignancies can be a safe procedure in terms of morbidity and mortality. METHODS: In a retrospective case-control study, the authors compared morbidity, mortality, and surgical data in a series of elderly patients (age > 70 years) with endometrial and ovarian carcinoma who underwent surgery. Patients were divided into two groups: Cases were 36 elderly patients who underwent surgery and pelvic and/or aortic lymphadenectomy and were matched with 72 controls, who were patients who underwent surgery without lymphadenectomy. RESULTS: Cases showed a significantly longer median operative time than controls (median, 162 minutes [range, 85-330 minutes] vs. median, 100 minutes [range 20-310 minutes], respectively; P = 0.003). No significant difference between the two groups in terms of blood loss, blood transfusions, intraoperative complications, duration of ileus, reintervention required, or postoperative hospital stay were observed. One patient in the control group died. The type and frequency of severe postoperative complications in the two groups were not substantially different. CONCLUSIONS: Pelvic and aortic lymphadenectomy was performed safely in elderly patients age > or = 70 years with endometrial and ovarian carcinoma without an increase in morbidity and mortality. Advanced chronologic age alone should not be considered a contraindication to full surgical treatment in these patients.

Expression of the retinoblastoma-related gene Rb2/p130 is downregulated in atypical endometrial hyperplasia and adenocarcinoma.

The retinoblastoma-related gene Rb2/p130 encodes a protein that is a negative cell-cycle regulator normally expressed in a number of adult tissues. This protein shares many structural and functional features with the product of the retinoblastoma gene, one of the best-studied tumor-suppressor genes, and plays a fundamental role in growth control. The Rb2/p130 gene product associates with specific members of the E2F family and various cyclins, displaying a growth-suppressive activity specific for the G(0)/G(1) phases. It has been reported that Rb2/p130 is involved in the pathogenesis and progression of lung cancer and mesothelioma. We previously demonstrated for the first time that reduced immunohistochemical expression of Rb2/p130 was a strong independent predictor of poor outcome in endometrial cancer. The aim of the present study was to evaluate Rb2/p130 expression in normal, hyperplastic, and neoplastic endometrial lesions to determine whether the protein plays a significant role in endometrial carcinogenesis. We evaluated Rb2/p130 expression by immunohistochemistry staining in 102 specimens chosen to represent a spectrum of endometrial changes, including proliferative endometrium (n = 18), secretory endometrium (n = 18), simple or complex hyperplasia without atypia (n = 18), atypical hyperplasia (n = 18), and invasive carcinoma (n = 30). We found that Rb2/p130 was highly expressed in proliferative endometrium and in hyperplasia without atypia, the mean percentage of stained nuclei being 66% and 60%, respectively, but was downregulated in secretory endometrium, atypical hyperplasia, and carcinoma, with mean scores of 38%, 25%, and 22%, respectively. When categorized on a semiquantitative scale (negative v 1% to 50% v >50% positivity), endometrial cancer displayed significantly less staining than all other endometrial samples (P <.001). Poorly differentiated carcinomas (n = 9) showed a significantly lower immunoreactivity for Rb2/p130 than did well-differentiated carcinomas (n = 11; P =.005) and moderately differentiated carcinomas (n = 10; P =.03). In addition, atypical hyperplasia showed a significantly lower immunoreactivity than either proliferative endometrium (P =.003) or hyperplasia without atypia (P = 0.02). Our findings of a progressive decrease in Rb2/p130 expression from hyperplastic endometrium through atypical hyperplasia to poorly differentiated carcinomas suggest the involvement of this negative cell-cycle regulator in endometrial carcinogenesis. Furthermore, immunostaining for Rb2/p130 may prove diagnostically useful in the often difficult distinction between hyperplastic and atypical hyperplastic endometrium. HUM PATHOL 32:360-367.

Eating attitudes and behavior throughout the menstrual cycle in obese women: a case-control study.

Premenstrual variations of eating behavior are reported in several studies, but their relationship with mood is unclear. Eating behavior and physical and psychological complaints during the menstrual cycle were studied in 107 obese patients and 93 matched controls using retrospective (Weekly Bulimic Test Edinburgh, W-BITE and Premenstrual Assessment Form, PAF) and prospective (Daily Rating Form, DR) questionnaires. Eating disorder symptoms increased in the premenstrual phase, as shown by the W-BITE scores both in patients (6.2 +/- 5.3 premenstrual week vs 4.9 +/- 4.4 postmenstrual week, p < 0.05) and in control subjects (4.9 +/- 4.1 premenstrual week vs 4.2 +/- 3.0 postmenstrual week, p < 0.05) and were correlated to premenstrual complaints in control subjects (r = 0.5; p < 0.05) but not in obese women (r = 0.2; p = NS). A close relationship between physical and psychological premenstrual disturbances was observed in obese patients only. Premenstrual variation of eating behavior could be the target of specific treatment.

Giant pelvic retroperitoneal liposarcoma.

BACKGROUND: Pelvic retroperitoneal liposarcomas are rare in young women (under 30 years old). We present a case of a giant well-differentiated liposarcoma of the retroperitoneum in a young woman. CASE: A 27-year-old nulligravida presented with rapid abdominal enlargement. Pelvic examination found a huge mass extending from the left adnexa to the epigastric region. At surgery, the pelvic organs were displaced to the right side by a retroperitoneal mass that marginally involved the left fallopian tube. The left ovary, uterus, and right adnexa were not involved and were not removed. No adjuvant irradiation was given. The patient was alive and well 2 years after the operation and was 23 weeks pregnant. CONCLUSION: Gynecologists should be familiar with pelvic retroperitoneal liposarcomas and their treatment.

Extraperitoneal pelvic lymphadenectomy to complement vaginal operations for cervical and endometrial cancer.

OBJECTIVE: The aim of the current study was to test the applicability of a personal modification of Mitra extraperitoneal pelvic lymphadenectomy in combination with radical vaginal operations for treatment of endometrial and cervical cancer. METHOD: In a prospective series, 82 patients were submitted to extraperitoneal pelvic lymphadenectomy. In 34 cases of stage I endometrial cancer the procedure was combined with a class I vaginal hysterectomy and in 48 cases of cervical cancer stage Ib-IIIb lymphadenectomy was associated with a class II or III radical vaginal hysterectomy. Type of anesthesia, number of lymph nodes removed, operating time, blood loss and postoperative complications were recorded. RESULT: The operation was performed with spinal anesthesia in 43% of the cases. Thirty-seven patients (45%) were high surgical risk because of associated diseases. The median operative time for lymphadenectomy was 20 min for each side; the vaginal procedures took a median of 25 min (class I) and 40 min (class II-III). Blood transfusions were necessary in seven cases (8. 5%). A median of 26 lymph nodes were removed from each patient. Lymphocyst occurred in seven patients (8.5%), retroperitoneal hematoma in two and retroperitoneal abscess in one. CONCLUSION: Extraperitoneal pelvic lymphadenectomy has proven to be a safe and quick technique to complement vaginal operations for endometrial and cervical cancer. Specific features of this approach are: (1) fast, timesaving procedure; (2) possible use of spinal anesthesia; and (3) applicability in high surgical risk patients.

Gynecologic oncologic surgery in the elderly: A retrospective analysis of 213 patients.

OBJECTIVES: The aims of the study were (1) to analyze morbidity and mortality for elderly women (>/=70 years) operated on for gynecological malignancies at our department between 1985 and 1996; and (2) to compare two periods of time (years 1985-1990 versus years 1991-1996) to investigate whether new expedience in the surgical technique as well as in the perioperative management introduced by 1991 influenced the feasibility and tolerability of surgery in elderly patients. METHODS: In a retrospective analysis, we evaluated tumor site, comorbidities, surgical features, morbidity, and mortality. By 1991, several modifications in management were introduced, including: (1) early postoperative mobilization; (2) self-donation with autologous blood transfusion; (3) intraoperative antibiotic prophylaxis; (4) the retroperitoneum was left open and drains were not used after pelvic and aortic lymphadenectomy; (5) use of coagulator forceps and hemoclips for meticolous hemostasis. RESULTS: In 213 patients, tumor site distribution was uterine corpus n = 93, ovary n = 51, vulva n = 29, cervix n = 23, breast n = 15, and vagina n = 2. There were advanced stage diseases in 47%, comorbid illnesses in 76%, and high surgical risk in 48%. Sixty-nine patients (group A) and 144 patients (group B) were treated in the first and second study periods, respectively. Overall, severe postoperative morbidity and mortality were 17 and 2.8%, respectively. Group B compared to group A showed more frequent use of major surgical procedures (P < 0.01) and lymphadenectomy (P < 0.04), lower transfusion rate (P < 0.001), reduced severe morbidity (P < 0.002), lower mortality (P = 0.3), and shorter hospital stay (P < 0.001). CONCLUSIONS: Our study suggests that surgery, including very radical procedures, is reasonably feasible and well tolerated by elderly patients. The introduction of technical and medical advances in the later years of the study resulted in a significant improvement of surgical rates.

Preoperative evaluation of tumor ploidy in endometrial carcinoma: An accurate tool to identify patients at risk for extrauterine disease and recurrence.

BACKGROUND: Tumor ploidy is a strong prognostic factor in patients with endometrial carcinoma, but generally is evaluated only after surgery. The availability of a simple and reliable method to determine tumor ploidy before any treatment is initiated could be helpful in the selection of patients at high risk for advanced primary disease and subsequent recurrence, with several possible benefits. The objectives of the current study were: 1) to test the accuracy of flow cytometric determination of tumor ploidy from preoperative outpatient endometrial biopsies compared with standard postoperative evaluation from the surgical specimen and 2) to correlate this preoperative parameter with the local recurrence and extrauterine tumor spread. METHODS: Tumor ploidy from both preoperative biopsy material and the macroscopic surgical specimens was evaluated prospectively in 50 consecutive patients with endometrial carcinoma. DNA analyses were performed in a blind fashion. Patients were followed for a median of 26 months (range, 16-46 months). RESULTS: In 9 of 50 cases (18%) an aneuploid tumor was found by the standard postoperative analysis. All 9 aneuploid tumors (100%) also were identified correctly by the preoperative test on biopsy material. Occult extrauterine tumor spread was found in 10 patients (20%). The incidence rate of aneuploidy among these tumors was 50% compared with 10% in surgical International Federation of Gynecology and Obstetrics Stage I tumors (P = 0.01). The recurrence rate was 55.5% (5 of 9 tumors) in the aneuploid group and 2.4% (1 of 41 tumors) in the diploid group (P < 0.001). The disease free survival rates of patients with diploid and aneuploid tumors were 97.5% and 44.4%, respectively (P < 0.0001). CONCLUSIONS: Preoperative tumor ploidy determination based on outpatient endometrial biopsy is as accurate as the standard postoperative evaluation in patients with endometrial carcinoma. Tumor aneuploidy confirms the usefulness of this method in selecting patients at risk for occult extrauterine tumor diffusion and recurrence.

[The "age factor" in ovarian cancer. Clinical, therapeutic and prognostic aspects]. / Il "fattore età" nei carcinomi dell'ovaio. Considerazioni cliniche, terapeutiche, prognostiche.

115 patients affected by ovarian tumors, were studied retrospectively, each with a follow-up of a minimum of 5 years. These cases were subdivided into two subgroups according to the age (younger or older than 65 years) to value the differences, from a prognostic and therapeutic point of view about the age of neoplasm onset. In patients older than 65 years, there were prevalent cases with worse prognosis, linked both to the neoplasm (greater incidence of advanced stages at the moment of the diagnosis; prevalence of tumours of low degree of differentiation), and to the treatment given (less destroying intervention, with a higher frequency of non optimal residual disease; fewer chemotherapeutic cycles for every patient, with lower doses and fewer times of administration of drugs; higher incidence of phenomena of resistance and rejection of the I line therapy). The survival curves were significantly different in the two groups of patients, proving a worse prognosis for older women. At last, a multivaried statistical analysis, revealed that age, like stage, residual disease and the number of chemotherapeutic cycles performed, represent an independent prognostic factor.

Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer.

PURPOSE: The retinoblastoma gene is the prototype of tumor-suppressor genes and has been shown to be involved in the pathogenesis and progression of several human malignancies. In this study, we determined the relation between the expression of a newly discovered retinoblastoma-related gene Rb2/p130 and outcome in patients with endometrial carcinoma. PATIENTS AND METHODS: pRb2/p130 expression was determined immunohistochemically in specimens of endometrial carcinoma (stages I to IV) from 100 patients who underwent surgery as the first treatment. The pRb2/p130 status was analyzed in relation to the length of disease-free survival and disease-specific survival. RESULTS: Decreased levels of pRb2/p130 in endometrial cancer cells was significantly associated with a decreased probability of remaining disease-free after treatment (P = .003) and with decreased probability of survival (P < .0001). In a multivariate analysis, pRb2/p130 status (P = .004), tumor stage (P = .009), and ploidy status (P = .02) were independent predictors of clinical outcome. The risk of dying of disease was increased substantially (risk ratio, 4.91; 95% confidence interval, 1.66 to 14.54) among patients with decreased levels of pRb2/p130 in tumor cells. CONCLUSION: In patients with endometrial carcinoma who did not receive radiotherapy or chemotherapy before surgery, the presence of decreased levels of pRb2/p130 in tumor cells is associated with a significantly increased risk of recurrence and death of disease, independent of tumor stage and ploidy status.

Identification, characterization, and biological activity of endothelin receptors in human ovary.

We previously reported the expression of endothelin-1 (ET-1) in granulosa cells (GCs) of the human ovary and the presence of ET-1-like immunoreactivity in human follicular fluid obtained from women in an in vitro fertilization program. In follicular fluid, but not in plasma, the levels of ET-1-like immunoreactivity were higher in gonadotropin-stimulated vs. spontaneous cycles, suggesting hormonal regulation of follicular ET-1. To identify and characterize ET receptors in human ovary, we performed autoradiography, radioligand binding, and functional studies. Mathematical analysis of families of self- and cross-competition curves among [125I]ET-1, [125I]ET-3, and selective analogs indicates that human ovary expresses both subtypes of ET receptors, i.e. ETA and ETB receptors. However, the concentration of the ETB site was 100-fold lower than that of the ETA one. By using [125I]ET-1, we demonstrated that the density of binding sites in human ovary is not affected by the hormonal milieu (similar concentrations in normal cycling, postmenopausal, and combined oral contraceptive-treated women). In situ binding studies indicate that the majority of ETA and ETB receptors are expressed in the blood vessels of the ovary. In particular, ETA receptors are abundant in the ovulatory follicles and localized in the theca interna, in close proximity to the granulosa layer. Few GCs of the ovulatory follicle were specifically labeled. Conversely, in the rat ovary, used as a control, ETB receptors were predominantly expressed and localized in GCs. Accordingly, ETB receptors negatively regulated estrogen accumulation in rat GCs. In human granulosa-luteal cells, neither ET-1 (unselective ligand) nor ET-3 or sarafotoxin 6c (ETB ligands) affected estrogen or progesterone secretion. ET-1 was 2.5-fold more potent than noradrenaline in eliciting contraction of ovarian artery, acting through the ETA receptor. Our results indicate that in human ovary, at variance with rat ovary, the endothelin system is primarily involved in the regulation of ovarian blood flow and not steroidogenesis.