Surgery improves survival in elderly with breast cancer. A study of 465 patients in a single institution.

INTRODUCTION: Breast cancer treatment in elderly patients is controversial. This single-centre study was conducted to review the treatment and outcomes for octogenarian women treated for breast cancer. METHODS: Data from all patients aged 80 years or more with primary breast cancer treated at our institution between 1995 and 2012 were included. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. RESULTS: The study population consisted of 369 patients (median age 84 years). A total of 277 (75%) patients underwent surgical treatment (PST) and 92 (25%) received primary endocrine treatment (PET). Prognostic factors (HER-2, tumour grade, lymphovascular invasion and subsequent adjuvant therapy) were homogeneously distributed in both groups. PST and PET were stratified according to stage: 273 (66%) patients with early stage disease (I, IIA, IIB) and 96 (34%) with locally advanced disease (IIIA, IIIB, IIIC). Patients were followed-up for a median of 63 months. In patients with early stage disease, the mean breast cancer-specific survival (BCSS) was 109 months (95% CI = 101-115) in PST patients, and 50 months (95% CI = 40-60) in PET patients (P < 0.01). Conversely, for patients with locally advanced breast cancer, there was no significant difference in BCSS between the surgical and non-surgical groups. In the PST group, BCSS and disease-free survival were significantly better among patients who underwent standard surgical treatment than among those who received suboptimal treatment. There were no differences in the Charlson comorbidity index scores between the PST and PET groups. CONCLUSION: In women ≥80 years with early-stage breast cancer, standard surgical treatment was associated with a better BCSS when compared with PET.

Prediction of non-sentinel lymph node metastasis in early breast cancer by assessing total tumoral load in the sentinel lymph node by molecular assay.

INTRODUCTION: The one-step nucleic acid amplification (OSNA) is a molecular procedure that yields a semiquantitative result for detection of nodal metastasis. Size of metastasis in the sentinel lymph node (SLN) by conventional histology has been described as a predictive factor for additional axillary metastasis. The objective of this study is to quantify intraoperatively the total tumoral load (TTL) in the positive SLNs assessed by OSNA and to determine whether this TTL predicts non-SLN metastasis in patients with clinically node negative early stage breast cancer. METHODS: 306 patients with cT1-3N0 invasive breast cancer who had undergone intraoperative SLN evaluation by OSNA were included. TTL was defined as the addition of CK19 mRNA copies of each positive SLN (copies/µL). RESULTS: TTL was a predictive factor of additional non-SLN metastasis in the complete axillary lymph node dissection (cALND) (OR, 1.67; 95% CI, 1.18-2.35). In the multivariate analysis, the TTL was a predictor of non-SLN metastasis in HR positive patients (OR, 1.69; 95% CI, 1.19-2.41). In our cohort of patients, with a TTL ≤1.2 × 10(5) copies/µL, there was a specificity of 85.3% and negative predictive value (NPV) of 80%. If we consider only the HR positive patients, with a TTL ≤5 × 10(5) copies/µL there was a specificity of 86.7% and NPV of 83.7%. CONCLUSIONS: TTL assessed by OSNA assay predicts for additional non-SLN metastasis and this intraoperative tool can help guiding decisions on performing a cALND in breast cancer patients.

The EMT signaling pathways in endometrial carcinoma

Endometrial cancer (EC) is the most common gynecologic malignancy of the female genital tract and the fourth most common neoplasia in women. In EC, myometrial invasion is considered one of the most important prognostic factors. For this process to occur, epithelial tumor cells need to undergo an epithelial to mesenchymal transition (EMT), either transiently or stably, and to differing degrees. This process has been extensively described in other types of cancer but has been poorly studied in EC. In this review, several features of EMT and the main molecular pathways responsible for triggering this process are investigated in relation to EC. The most common hallmarks of EMT have been found in EC, either at the level of E-cadherin loss or at the induction of its repressors, as well as other molecular alterations consistent with the mesenchymal phenotype-like L1CAM and BMI-1 up-regulation. Pathways including progesterone receptor, TGFβ, ETV5 and microRNAs are deeply related to the EMT process in EC (AU)

Location of aortic node metastases in locally advanced cervical cancer.

BACKGROUND: To assess the location of aortic node metastasis in patients with locally advanced cervical cancer undergoing extraperitoneal aortic lymphadenectomy to define the extent of the aortic lymphadenectomy. MATERIAL AND METHODS: Between August 2001 and December 2010, 100 consecutive patients with primary locally advanced cervical cancer underwent extraperitoneal laparoscopic aortic and common iliac lymphadenectomy. The location of aortic node metastases, inframesenteric or infrarenal was noted. RESULTS: The mean number±standard deviation (SD) of aortic nodes removed was 15.9 ± 7.8 (range 4-62). The mean number ± SD of inframesenteric (including common iliac) nodes removed was 8.8 ± 4.5 (range 2-41) and the mean number ± SD of infrarenal nodes removed was 7.8 ± 4.1 (range 2-21). Positive aortic nodes were observed in 16 patients, and in 5 (31.2%) of them the infrarenal nodes were the only nodes involved, with negative inframesenteric nodes. CONCLUSION: Inframesenteric aortic nodes are negative in the presence of positive infrarenal nodes in about one third of patients with locally advanced cervical cancer and aortic metastases.

Breast conservative surgery after neoadjuvant chemotherapy in breast cancer patients: comparison of two tumor localization methods.

AIMS: The key to surgical planning for breast conservative treatment (BCT) after neoadjuvant chemotherapy (NAC) is tumor localization. Tumor marking can be performed using either skin tattoo or metallic marker. The objective of this study is to compare both types of tumor localization markers and to assess which techniques improve BCT in achieving a complete resection without compromise margins. METHODS: 149 patients between 1999 and 2009 were eligible for the study. The skin tattoo group (TG) included 118 patients and the metallic marker group (MG) included 31 patients. Both markers were placed before starting NAC. RESULTS: Median clinical tumor volume was 10.3 cm(3) in the TG and 22.4 cm(3) in the MG (p = 0.051). After NAC treatment, there were no significant statistically differences in both groups regarding complete clinical response, partial clinical response, and complete and partial pathological response. Median pathological tumor volume was: 0.8 cm(3) in the TG and 0.69 cm(3) in the MG (p = 0.8). Lumpectomy volume was bigger in the TG (268 cm(3)) than MG (143 cm(3)); p < 0.004. There were no statistically significant differences when comparing margin status. CONCLUSIONS: Lumpectomy guided with metallic marker after NAC allows lower excision of breast tissue without compromising margins. Having similar pathologic response between groups, skin tattoo leads to excise larger volume of tissue adding no benefits to the surgery. With the increasing pathologic complete responses to NAC, patients who are candidates for BCT after NAC will benefit from marking the tumor with metallic markers.

Can we predict local recurrence in breast conserving surgery after neoadjuvant chemotherapy?

BACKGROUND: One of the benefits of neoadjuvant chemotherapy (NAC) is its ability to convert patients ineligible for breast conservative treatment (BCT) to be candidates for this treatment, although questions have been raised regarding the effectiveness of BCT in terms of loco-regional recurrence (LRR). The objective of this study is to evaluate LRR in this group and the influence of tumor characteristics in recurrence. MATERIAL AND METHODS: Between 1996 and 2007, 137 patients were treated with BCT after NAC at our Service. After completion of NAC a multidisciplinary team evaluated the cases eligible for BCT. All patients treated with BCT had negative margins and received radiation therapy. Risk factors associated with local recurrence were analyzed using Kaplan-Meier survival curves and long-rang test. RESULTS: Information was obtained in 121 patients. Median age was 54 years old (SD: 12 years). At a median follow-up of 35 months (range, 18-87 months), 6 (4.95%) patients developed an LRR, with an accumulative incidence at 5 years of 7.3% (95% CI: 0.4-14.1%) and at 10 years of 11.5% (95% CI: 2.8-20.1%). Overall survival at 5 and 10 years was 94.8% (95% CI: 90.9-98.6%) and 82.3% (95% CI: 67.3-97.2%) respectively. Tumor size (T3) (p < 0.001) and pathological stage (Stage III) (p = 0.001) after surgery were strongly associated with LRR. CONCLUSIONS: The results of this study confirm that BCT is an effective treatment in patients with NAC. Tumor size and pathological stage after systemic treatment influence loco-regional recurrence in patients with BCT.

Out-of-protocol concurrent use of cisplatin and radiation therapy in locally advanced cervical cancer: feasibility and survival.

PURPOSE OF INVESTIGATION: We assessed the feasibility, response rates, and overall survival of patients with locally advanced cervical cancer treated with cisplatin-based chemotherapy during radiation therapy on an out-of-protocol basis. METHODS: Sixty-nine consecutive newly diagnosed untreated patients with locally advanced cervical cancer who received chemoradiation between 1999 and 2003 were retrospectively reviewed. Treatment consisted in external beam radiation followed by one 137-cessium intracavitary application. Cisplatin was administered for six weeks during external beam radiation. RESULTS: Treatment was well tolerated, although 52 patients presented some degree of acute adverse toxicity (gastrointestinal 65%, hematological 48%, genitourinary 10%). The 3-year survival rate was 61.8% (95% CI 54.5-69.0), with a mean 41.8 months (95% CI 35.7-48.3). Overall survival after adjusting by FIGO Stage IB2-IIA and IIB-IVA was 73.9% and 50%, respectively (p = 0.1839). Overall survival according to Stages IB2-IIb and III-IVA was 74.8% and 34.9%, respectively (P = 0.0376). CONCLUSION: In patients with locally advanced cervical cancer, adding a weekly regimen of cisplatin to standard pelvic radiation in an out-of-protocol basis is feasible, effective, and showed no unexpected toxicity.

Removal of all radioactive sentinel nodes in breast cancer improves the detection of positive sentinel nodes.

OBJECTIVE: The aim of this study is to evaluate if it is necessary to remove all the radioactive sentinel lymph nodes (SLNs) not seen on lymphoscintigraphy in order to accurately stage breast cancer patients. MATERIAL AND METHODS: From March 1999 to March 2006, SLN biopsy was performed in 461 patients. All patients were only injected with radioisotope. Lymphoscintigraphy was performed in all the patients. The mean number of SLNs removed was 2.1 (range 1-15). RESULTS: The SLN was positive in 133 patients (28.8%). Lymphoscintigraphy accurately predicted the number of SLNs identified intraoperatively in 243 patients (52.7%). In 175 patients (37.9%) there were more SLNs identified intraoperatively than were seen on lymphos cintigraphy. In 11 (6.2%) of these 175 patients, additional SLNs identified intraoperatively harboured metastasis. Type of injection, need for a second injection, tumour location and age were not identified as statistically significantly associated with additional positive SLNs identified intraoperatively and not seen on lymphoscintigraphy. CONCLUSIONS: Lymphoscintigraphy does not accurately predict the number of SLNs identified intraoperatively, this number being underestimated. Surgeons should remove all radioactive SLNs to improve the detection of positive SLNs.

Removal of all radioactive sentinel nodes in breast cancer improves the detection of positive sentinel nodes

OBJECTIVE: The aim of this study is to evaluate if it is necessary to remove all the radioactive sentinel lymph nodes (SLNs) not seen on lymphoscintigraphy in order to accurately stage breast cancer patients. MATERIAL AND METHODS: From March 1999 to March 2006, SLN biopsy was performed in 461 patients. All patients were only injected with radioisotope. Lymphoscintigraphy was performed in all the patients. The mean number of SLNs removed was 2.1 (range 1-15). RESULTS: The SLN was positive in 133 patients (28.8%). Lymphoscintigraphy accurately predicted the number of SLNs identified intraoperatively in 243 patients (52.7%). In 175 patients (37.9%) there were more SLNs identified intraoperatively than were seen on lymphos cintigraphy. In 11 (6.2%) of these 175 patients, additional SLNs identified intraoperatively harboured metastasis. Type of injection, need for a second injection, tumour location and age were not identified as statistically significantly associated with additional positive SLNs identified intraoperatively and not seen on lymphoscintigraphy. CONCLUSIONS: Lymphoscintigraphy does not accurately predict the number of SLNs identified intraoperatively, this number being underestimated. Surgeons should remove all radioactive SLNs to improve the detection of positive SLNs (AU)

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Novel molecular profiles of endometrial cancer-new light through old windows.

Endometrial carcinoma (EC) is the most common gynecological malignancy in the western world. A widely accepted dualistic model, which has been established on a morphological basis, differentiates EC into two broad categories: Type I oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II non-oestrogen-dependent EC with a serous papillary or clear cell morphology. Molecular genetic evidence indicates that endometrial carcinoma, as described in other malignancies, likely develops as the result of a stepwise accumulation of alterations in cellular regulatory pathways, such as oncogene activation and tumor suppressor gene inactivation, which lead to dysfunctional cell growth. These molecular alterations appear to be specific in Type I and Type II cancers. In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction with defects in DNA mismatch repair genes, as evidenced by the microsatellite instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are recognized major alterations, which define the progression of the normal endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu and seem to arise from a background of atrophic endometrium. Nevertheless, despite the great effort made to establish a molecularly-based histological classification, the following issues must still be clarified: what triggers the tumor cells to invade the myometrium and what causes vascular or lymphatic dissemination, finally culminating in metastasis? RUNX1, a transcription factor, was recently identified as one of the most highly over-expressed genes in a microarray study of invasive endometrial carcinoma. Another candidate gene, which may be associated with an initial switch to myometrial infiltration, is the transcription factor ETV5/ERM. These studies, as well as those conducted for other genes possibly involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, could help in understanding the differences in the biology and the clinical outcome among histological types.

Molecular determinants of invasion in endometrial cancer.

Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis.

Molecular determinants of invasion in endometrial cancer

Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis (AU)

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Sentinel lymph node identification in a primary ductal carcinoma arising in the vulva.

Primary or metastatic breast-like carcinoma of the vulva is a rare event. Because of the similarity with breast ductal carcinoma, we think that the same principles used for treatment of orthotopic breast cancer can be applied, as well as the use of sentinel lymph node technique, which is widely accepted in the management of early-stage breast cancer. We report a 49-old-year postmenopausal woman who was referred to our institution after small biopsy of a 3.5- x 3-cm right vulvar tumor. Histopathologically, infiltration of the vulvar dermis by a ductal carcinoma of mammary gland type was reported. At operation, the sentinel node technique revealed two sentinel nodes in the right inguinal area. Although these nodes proved negative for malignancy, the patient underwent wide local excision of tumor and complete ipsilateral inguinofemoral lymphadenectomy. The remaining excised nodes were negative. Surgical specimen proved estrogen- and progesterone-positive receptors, the reason for which the patient received tamoxifen adjuvant therapy. This report represents the first case in the world literature of primary breast carcinoma arising in the vulva in which sentinel lymph node identification has been possible. Because of the rarity of this condition, the pathologic similarity of this tumor along with currently accepted guidelines for the management of breast cancer supports the possibility of local excision and sentinel lymph node identification as a possible alternative to inguinofemoral lymphadenectomy.

Modified approach for extraperitoneal laparoscopic staging for locally advanced cervical cancer.

Describe a modified approach to the technique for staging laparoscopic extraperitoneal aortic and common iliac lymph node dissection for locally advanced cervical cancer.Retrospective, nonrandomized clinical study. (Canadian Task Force classification II-2), setting in an acute-care, teaching hospital. Thirty-six patients with locally advanced cervical cancer underwent laparoscopic surgical staging via extraperitoneal approach with the conventional or the modified technique from August 2001 through September 2004. Clinical outcomes in 23 patients who were operated on with the conventional technique using index finger for first trocar entrance; 12 patients with the modified technique using direct trocar entrance, were compared. One patient was excluded due to peritoneal carcinomatosis. Technique, baseline characteristics, histopathologic variables and surgical outcome were measured. There were no significant differences in patients basal characteristics on comparative analysis between conventional and modified technique. With our proposed modified technique, we obtained a reduced surgical procedure duration and blood loss. The proposed modified surgical technique offers some advantages, is an easier approach because the parietal pelvic peritoneum is elastic and this helps to avoid its disruption at time of trocar insertion, size of incision is shorter, we achieved no CO2 leak through the trocar orifice, and wound suture is fast and simple.

Histerectomía en oncología ginecológica / Hysterectomy in gynaecological oncology

En este capítulo se revisan las indicaciones de histerectomía en todos los tipos de cáncer ginecológico

Indications of hysterectomy in all types of gynaecological cancer are reviewed in this chapter

Extraperitoneal laparoscopic para-aortic lymphadenectomy for lymph node recurrence of fallopian tube carcinoma.

The endoscopic retroperitoneal approach is a minimally invasive method for surgical staging of cervical cancer. A 57-year-old woman had an intraoperative diagnosis of carcinoma of the left fallopian tube and undergone a retroperitoneal pelvic and para-aortic lymphadenectomy with no peritonization during surgical staging. Small suspicious nodes in the serous membrane of the sigmoid colon and peritoneal washings were positive for malignancy. A total of 12 nodes were obtained, all of which were negative. She received six cycles of paclitaxel and platinum-based chemotherapy and showed a complete clinical response. Thirty-two months after surgery, the abdominal computed tomography scan showed a left para-aortic lymph node, 19 mm in diameter, which was successfully removed through an extraperitoneal laparoscopic approach. The extraperitoneal laparoscopic approach of the para-aortic region is a feasible procedure after previous transperitoneal lymphadenectomy and chemotherapy.

Molecular pathology of endometrial carcinoma: transcriptional signature in endometrioid tumors.

A dualistic model, which has been established on a morphological basis and that differentiates type I endometrioid from type II non-endometrioid endometrial cancer, is widely accepted. Molecular genetics have provided us with data supporting the dualistic model of endometrial tumorigenesis and with some clues to speculate about the sequence of the molecular alterations defining the tumorigenesis pathways. In type I endometrioid endometrial cancer, PTEN gene silencing, microsatellite instability associated with defects in DNA mismatch repair genes, or mutations in the K-ras gene are the known major alterations defining the progression from normal endometrium to hyperplasia and then on to carcinoma. Recently, cDNA microarray technology for identifying the differences in gene expression patterns between the histological types of endometrial cancer have permitted the identification of differentially expressed genes that could help us to understand differences in the biology and the clinical outcome between histiotypes. Genes involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, or altered genes associated with the initial steps of myometrial infiltration in endometrioid endometrial cancer, represent examples of how useful large genetic screenings can be for understanding the tumorigenesis process and the future directions in the molecular pathogenesis of endometrial cancer.

Usefulness of sentinel lymph node detection in early stages of cervical cancer.

PURPOSE: Sentinel lymph node (SLN) mapping in combination with surgical biopsy is an emerging technique for use in the early stages of cervical cancer. The purpose of this study was to evaluate the technique in a series of 40 consecutive women with early stage cervical cancer. METHODS: Forty patients with early stage cervical cancer [FIGO stage IA2 (2), IB1 (34), IB2 (1) or IIA (3)] were referred for radical hysterectomy with pelvic lymphadenectomy. Patients were submitted to preoperative lymphoscintigraphy (four 99mTc-nanocolloid injections around the tumour) and intraoperative SLN detection. Hand-held or laparoscopic gamma probes were used to locate SLNs during surgery. RESULTS: The mean number of SLNs was 2.5 per patient (interiliac 49%, external iliac 19%). Of the total of 99 SLNs, six, in four women, showed metastases (all 68 non-SLNs removed were negative). In the other 36 patients, all the removed lymph nodes (sentinel and non-sentinel) were negative (0% false negative rate). During the follow-up (median 25 months), only two patients presented distant metastases: one died 6 months after surgery (two of three SLNs positive, both hot and blue), while the second patient is alive 4 years after surgery (lung metastasis, no isotope drainage, negative blue SLN). The survival rate was 95% and disease-free survival, 97%. CONCLUSION: SLN surgical biopsy based on lymphoscintigraphy and blue dye is a feasible and useful technique to avoid lymph node dissection in the early stages of cervical cancer. It has a high negative predictive value, can be incorporated into clinical routine (laparoscopy or open surgery) and is close to achieving validation in this setting.

Endometrial cancer in polyps: a clinical study of 27 cases.

PURPOSE OF INVESTIGATION: To review risk factors, clinical presentation, diagnostic methods, and histopathologic findings in 27 cases of endometrial cancer in polyps. METHODS: A descriptive, retrospective study of 204 consecutive patients with endometrial carcinoma who were diagnosed at our institution between June 1998 to June 2001. Endometrial cancer arising in polyps occurred in 27 patients (13.2%) and accounted for 1.8% of 1492 endometrial polyps diagnosed during this period. RESULTS: Patients had a mean age of 62 years. All except one woman were postmenopausal. Three breast cancer patients were currently given tamoxifen. Metrorrhagia was the presenting symptom in 74% of cases, although 22% of patients were asymptomatic at the time of diagnosis. Ultrasonography performed in 22 patients showed images compatible with an endometrial polyp in 50% of cases, myoma in 5%, and inconclusive findings in 45%. The median endometrial thickness was 11 mm (range 4-33 mm). Diagnosis was made by aspiration-biopsy in 13 patients and by hysteroscopic endometrial sampling in 13 (in one patient endometrial carcinoma was incidentally found in the surgical specimen). All patients were in FIGO Stage IA. Endometrioid carcinoma was found in 81.5% of cases. Retroperitoneal metastases were not found in 25 patients undergoing pelvic lymphadenectomy, nor neoplastic growth in the specimens of six polypeptomies performed during hysteroscopy. All patients are free of relapse after a mean follow-up of 30 months. CONCLUSIONS: Postmenopausal women with endometrial polyps diagnosed by ultrasonography should undergo directed biopsies under hysteroscopic vision. The present series confirms the good prognosis of endometrial cancer in polyps.

Fibromatosis agresiva de localización mamaria: una rara entidad / Aggressive fibromatosis of the breast: a rare entity

Presentamos 2 pacientes con un tumor mamario cuyo diagnóstico, tras su extirpación quirúrgica, ha sido el de fibromatosis agresiva de localización mamaria. Es característica la falta de microcalcificaciones en la mamografía, y el diagnóstico suele realizarse tras la extirpación de la tumoración. El tratamiento de elección es la exéresis quirúrgica amplia del tumor. El estudio patológico pone de manifiesto una proliferación de células fibroblásticas sin atipia ni mitosis, que se organizan en fascículos largos o haces que rodean los lobulillos y conductos lobulillares. En cuanto a la evolución clínica, la característica más importante es la alta tendencia a la recidiva (AU)