Semi-quantitative evaluation of estrogen receptor expression is a strong predictive factor of pathological complete response after anthracycline-based neo-adjuvant chemotherapy in hormonal-sensitive breast cancer.

Absence of hormonal receptors (HR) expression is a predictive factor of high pathologic complete response (pCR) rate after neo-adjuvant chemotherapy. However, HR-positive tumors are less chemosensitive. In the present study, we evaluated the predictive value of estrogen (ER) and progesterone (PgR) semi-quantitative expression in patients with HR-positive tumors treated uniformly with antracycline-based neoadjuvant chemotherapy without hormonal treatment. Value of HR expression as a predictive factor was then evaluated in a multivariate analysis with tumor grade, Ki67 index and HER2 expression. From January 2000 and December 2006, 177 patients with HR-positive breast ductal invasive carcinoma ≥2 cm in its largest diameter were treated with six cycles of an anthracycline-based neo-adjuvant chemotherapy. Tumor grade, ER, PgR, HER2 status and Ki67 index were determined on microbiopsy performed before chemotherapy. A semi-quantitative evaluation of ER and PgR expression by IHC was performed using the Barnes'score. pCR rate was significantly different (P < 0.001) according to the ER expression score. pCR rate was 28% for low score, 9% for medium score and 3% for high score. On the contrary, pCR rate was not significantly different (P = 0.49) according to the PgR expression score. In the multivariate analysis, ER expression score (P = 0.0002) and Ki67 index (P = 0.02) were the only predictive factors of response for HR-positive tumors. pCR after anthracycline-based chemotherapy is significantly correlated with the ER expression score.

Value of fine-needle aspiration in evaluating large thyroid nodules.

BACKGROUND: The American Thyroid Association (ATA) recommends using ultrasound-guided fine-needle aspiration (FNA) in order to evaluate supracentimetric and suspect thyroid nodules. The purpose of this study was to evaluate the effective use of FNA before surgery for nodules over 3 cm in diameter. METHODS: In this retrospective study, we analyzed the results of ultrasound-guided FNA and postoperative histological analysis in 843 nodules >3 cm. RESULTS: The FNA was informative in 42.6%. The correlation with the final histological analysis was 94.8% for benign nodules and 71.0% for malignant nodules. The FNA had a positive predictive value of 71%, a specificity of 97%, a sensitivity of 56%, and a 4.7% rate of false-negative results. CONCLUSION: Because there is a nonnegligible FNA risk of error, notably allowing the evolution of a cancer in 1 of 20 cases, the FNA data should not delay surgical intervention for potentially suspect nodules >3 cm in diameter. © 2016 Wiley Periodicals, Inc. Head Neck 39: 32-36, 2017.

Unusual primary tumors presenting as papillary carcinomas metastatic to the neck.

The presence of a metastatic papillary carcinoma in the neck is presumptive evidence of a primary thyroid neoplasm since neck metastases of other primary tumors are uncommon. Immunohistochemical studies may be required to diagnose these metastases. We report 2 cases in which an unrelated tumor mimicked a thyroid malignancy. Both patients had been referred for evaluation of enlarged lymph neck nodes without any other symptoms. In both cases, a lymph node biopsy identified a metastatic papillary adenocarcinoma that was believed to be consistent with a thyroid primary. Thyroidectomy was not performed in either case. Further investigations led to the diagnosis of other primary tumors that were unrelated to the thyroid; the unrelated primaries were an ovarian serous tumor in one patient and a papillary renal cell carcinoma in the other.

Assessment of response by breast helical computed tomography to neoadjuvant chemotherapy in large inflammatory breast cancer.

Breast helical computed tomography (CT) was evaluated for use in assessing response to neoadjuvant chemotherapy and residual tumor volume. Forty-three patients with large, inflammatory breast cancers (stage IIA, 12; IIB, 13; IIIA, 9; IIIB, 9), all histologically confirmed by core biopsy, were evaluated prior to and following neoadjuvant chemotherapy. The breast helical CT procedure involved patients in the prone position using single acquisition during quiet respiration following intravenous injection of nonionic contrast material. Helical CT results (3.2-mm slices and maximum intensity projections) were compared to clinical and mammographic evaluations, as well as to pathologic findings. All tumors were clearly visible by breast helical CT, showing important tumor enhancement. Helical CT evaluation of response to chemotherapy (using World Health Organization criteria) corresponded better with mammography (78%, Cohen's kappa statistic (kappa) = 0.65) than with clinical examination (53%, kappa = 0.30). Helical CT measurement of residual tumor volume after neoadjuvant chemotherapy and correlation with pathologic findings were globally satisfactory. The intraclass correlation coefficient was 0.69 (excellent for rounded opacities [0.97], but not as good for diffuse, scattered or multinodular opacities [0.60]). By contrast, clinical and mammographic correlations were globally unsatisfactory (0.49 and 0.28, respectively). Breast helical CT can be very useful in the quantitative assessment of response to neoadjuvant chemotherapy and preoperative determination of residual tumor volume. For this reason, it can be considered an alternative to breast magnetic resonance imaging because of its simplicity, rapidity, and accessibility.

[Detection of the sentinel node by the surgeon]. / Le repérage du ganglion sentinelle par le chirurgien.

The sentinel node is detected by blue dye, radiocolloïd injection or by combined techniques. Before performing selective lymphadenectomy, a complementary axillary clearance is mandatory during the learning phase. This axillary mini-invasive surgery requires a close collaboration with the nuclear physicians, the pathologists and a training under expert teams leadership.

[Standards, Options and Recommendations 2000: non metastatic endometrial cancer]. / Standards, Options et Recommendations 2000: cancer de l'endomètre, stades non métastatiques (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Cancer Centers, and specialists from French Public Universities, General Hospitals and Private Clinics, and some specialists learned societies. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The SORs are developed using a methodology based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for the management of patients with carcinoma of the endometrium according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline , web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 63 independent reviewers. RESULTS: The main recommendations for the management of carcinoma of the endometrium are: 1) The diagnosis of carcinoma of the endometrium is based on biopsy and histological examination. However, as first intention, the first elements for diagnosis can be obtain from a hysterography, or particularly, a endovaginal ultrasound examination. Ultrasound allows locoregional metastases to be detected, the CT scan allows the lymph node involvement to be assessed and magnetic resonance imaging allows the myometrium invasion to be evaluated. 2) For the majority of patients, surgery is the initial treatment, both for localised and advanced-stage carcinomas. The excised sample can be used for pathological analysis and tumour staging, using the FIGO (Fédération internationale de gynécologie obstétrique) classification. Surgery for patients with stage I and II carcinomas involves total extrafascial hysterectomy with bilateral salpingo-oophorectomy., In patients with stage III and IV carcinomas radical surgery should be performed, when possible. If this is not possible, then surgery should be as complete as possible and be associated with a complementary treatment. In patients with the most advanced carcinomas, tumour reduction by surgery should be performed. 3) Complementary treatment includes external-beam radiotherapy and brachytherapy. The decision concerning the extent and type of irradiation should be taken taking into consideration the stage and the prognostic factors present. For patients with stage I and II carcinoma, complementary treatment with brachytherapy can be performed, if the myometrium invasion is not deep, or if the carcinoma is grade 2 or 3. Patients with stage III carcinomas can be treated with pelvic or abdominal-pelvic complementary irradiation. In patients that cannot undergo surgery, exclusive radiotherapy can be performed. 4) In the absence of any symptoms, surveillance should include a general clinical and gynaecological examination. All patients with symptoms should undergo an additional work-up.

Stimulation of breast cancer cell lines by post-surgical drainage fluids.

BACKGROUND/AIM: Surgery, which remains a conventional treatment of breast tumors, may induce the secretion of growth factors that support angiogenesis and wound healing. These factors are suspected to trigger carcinoma cell division and promote tumor relapse. We addressed this question by culturing breast cancer cell lines in the presence of wound fluid harvested after surgery. MATERIALS AND METHODS: Wound fluids were collected from patients who underwent either breast reconstruction, tumor resection, or tumor resection after neoadjuvant chemotherapy. MCF-7 (estrogen receptor (ER)+/progesterone receptor (PgR)+, HCC1937 (ER/PgR-, human epidermal growth factor receptor/neuralized (HER2/neu)-) and MCF-10A (used as a negative control) cell lines were grown in culture media supplemented with wound fluids. RESULTS: Wound fluids drained during the three categories of procedures significantly stimulated the proliferation of MCF-7 and HCC1937 cells in a similar manner. CONCLUSION: This stimulatory effect on tumor cell proliferation could be attenuated by therapeutic targeting against growth factors and inflammation processes in order to avoid tumor relapse.

A large retrospective multicenter study of vaginal melanomas: implications for new management.

The outcome of patients presenting with vaginal melanoma has been assessed in a large multicentric retrospective study. The databases of 12 French institutions were searched for primary vaginal melanomas managed between 1990 and 2007. Among the 54 patients recorded, 46 were managed with a curative intent and included in the study. The clinical characteristics, treatments, and detection of c-KIT protein expression have been studied. The median age of the patients was 63.5 years (42-88). Twenty-eight patients were classified as International Federation of Gynecology and Obstetrics (FIGO) stage I, five as stage II, six as stage III, and one as stage IVA. c-KIT protein was overexpressed in 80% of the patients. Forty-two patients underwent surgical resection of the tumor, nine patients received local adjuvant treatment, and 10 received systemic adjuvant therapy. The median relapse-free survival was 10.9 months. c-KIT-negative status (P=0.01) and stage I (P=0.02) were associated with locoregional recurrence. The rate of metastasis was increased for advanced FIGO stages (P<0.01). The median overall survival (OS) was 28.4 months. The finding of lymph node metastasis adversely affected OS (P<0.01). Conservative surgery and radiotherapy were associated with a decrease in metastasis-free and OS (P<0.01) compared with surgery alone, this group of patients presenting with advanced FIGO stages (P=0.02). Despite the use of limited data, conservative surgery combined with a sentinel lymph node procedure, followed by adjuvant radiotherapy could be proposed to patients with early FIGO stage in the absence of validated management. c-KIT negativity by immunochemistry appears to be a poor prognosis marker in terms of locoregional recurrences but not for metastatic spread nor survival. Further assessment of the role of c-KIT expression in this disease is thus mandatory to select patients for targeted therapy.

Main complications and results of treatment with intra-arterial infusion chemotherapy through the subclavian and thoracic arteries for locally advanced breast cancer.

Intra-arterial infusion chemotherapy for locally advanced breast cancer (LABC) has been previously performed. However, the main complications of this type of chemotherapy remain to be clarified. In the present study, catheterization chemotherapy was carried out for 53 LABC cases (stage IIIa-IIIc) between May, 2006 and March, 2007. For IIIB and IIIC patients, the catheters were guided to the opening of the subclavian artery. For stage IIIa patients, the catheters were placed into the thoracic artery through a subcutaneous femoral artery puncture. One to four cycles of chemotherapy (mean, 1.6 cycles) were administered for the patients using taxotere, epidoxorubicin, 5-fluorouracil and/or cyclophosphamide. The interval time between the two cycles was 21 days. Seven cases were identified as complete response (CR, 13.2%), 41 cases were partial response (PR, 77.4%) with a rate of effectiveness of (CR + PR, 90.6%), 5 cases were stable disease (SD, 9.40%) and no case was progressive. Pain of the ipsilateral upper extremity was present in 7 cases. Two cases exhibited ipsilateral upper extremity atrophy following drug administration from the opening of the subclavian artery. One case experienced neck pain and headache, while in one case necrosis of local skin was evident. Hematological toxicity over grade 3 was observed in 6 cases (11.30%). Systemic toxicity was mild and did not affect the quality of life of the patients. Overall survival was identified as 18/51 (35.3%), and free-disease survival as 10/51 (19.6%). In conclusion, intra-arterial infusion chemotherapy is an effective local control treatment for LABC. The main complications are pain of the ipsilateral upper extremity and neck as well as headache. Severe complications are ipsilateral upper extremity atrophy and necrosis of local skin. During the treatment, controlling the pressure of the tourniquet and velocity of drug administration are crucial for reducing local complications.

Sentinel lymph nodes fluorescence detection and imaging using Patent Blue V bound to human serum albumin.

Patent Blue V (PBV), a dye used clinically for sentinel lymph node detection, was mixed with human serum albumin (HSA). After binding to HSA, the fluorescence quantum yield increased from 5 × 10(-4) to 1.7 × 10(-2), which was enough to allow fluorescence detection and imaging of its distribution. A detection threshold, evaluated in scattering test objects, lower than 2.5 nmol × L(-1) was obtained, using a single-probe setup with a 5-mW incident light power. The detection sensitivity using a fluorescence imaging device was in the µmol × L(-1) range, with a noncooled CCD camera. Preclinical evaluation was performed on a rat model and permitted to observe inflamed nodes on all animals.

Thoracic duct fistula after thyroid cancer surgery: towards a new treatment?

The use of somatostatin analogs is a new conservative therapeutic approach for the treatment of chyle fistulas developing after thyroid cancer surgery. The combination therapy with a total parenteral nutrition should avoid the high morbidity of a re-intervention with an uncertain outcome. This promising trend is supported by the present case report of a chyle leak occurring after total thyroidectomy with central and lateral neck dissection for a papillary carcinoma, which was treated successfully without immediate or distant sequelae.

REG gamma: a potential marker in breast cancer and effect on cell cycle and proliferation of breast cancer cell.

To investigate the expression and significance of proteasomes reactivator REG gamma (γ) in breast cancer. First, we showed the expression of REGγ in breast cancer, metastatic lymph nodes and normal breast tissues. Meanwhile, we also analyzed the relationship between REGγ and estrogen receptor (ER), CerBb-2, lymph nodes metastasis and clinical stage of breast cancer. REGγ expression was determined by immunohistochemical staining and western blot. Secondly, we detected the expression of REGγ and REGγ-mRNA in human breast cancer cell lines (MDA-MB-231, MCF-7) and human breast ductal epithelial cell line (HBL-100) by western blot and real-time PCR. Finally, in order to identify effect of REGγ on breast cancer cell cycle and proliferation, we constructed recombinant plasmid of PcDNA3.1-REGγ and designed siRNA for REGγ in vitro. Cell cycle was assayed by flow cytometer (FCM), proliferation was measured by methyl thiazolyl tetrazolium (MTT). The results demonstrated abnormal high expression of REGγ in breast cancer and its metastatic lymph nodes. REGγ expression was related to breast cancer and its status of ER, CerBb-2 and lymph nodes metastasis. REGγ is one of the potential markers in breast cancer. REGγ could facilitate the growth of breast cancer cells.

Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature.

The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi (131)I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of (131)I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.

Role of intraoperative neuromonitoring of the recurrent laryngeal nerve in high-risk thyroid surgery.

BACKGROUND: Thyroid surgeries associated with an elevated incidence of recurrent laryngeal nerve (RLN) injury are considered high-risk thyroidectomies. These high-risk operations include surgery for thyroid cancer, Graves disease, and recurrent goitre. In addition, the size of the goitre is an important risk factor for RLN injury. OBJECTIVE: In our retrospective study, we tried to evaluate the role of intraoperative neuromonitoring of RLN specifically in high-risk thyroid surgery with 421 nerves at risk. METHOD: Thyroid surgeries in our study were done by experienced surgeons in a high-volume provider centre.The overall percentage of RLN injury was 8.8% in the monitored group in comparison with 9.1% in the unmonitored group. The percentage of permanent nerve palsy in the monitored group was 3.9% of nerves at risk in comparison with 3.8% in the unmonitored group. No statistically significant difference was found between groups. CONCLUSION: Routine visual identification of the nerve by meticulous dissection is the best method to avoid RLN injury. The benefit of RLN neuromonitoring could be further assessed by performing a multicentre prospective study to compare the role of RLN neuromonitoring in high-risk thyroid surgeries.

Prospective multicentric randomized study comparing periareolar and peritumoral injection of radiotracer and blue dye for the detection of sentinel lymph node in breast sparing procedures: FRANSENODE trial.

PURPOSE: To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer. PATIENTS AND METHODS: A prospective randomized multicentric study was initiated to compare the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients. RESULTS: The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001). CONCLUSION: This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.

Randomized multicentric study of perioperative chemotherapy with mitoxantrone in early breast cancer.

BACKGROUND: To confirm the hypothesis that reducing the interval between surgery and adjuvant chemotherapy could improve prognosis, a randomized multicentric study of adjuvant perioperative chemotherapy (POC) in breast cancer was initiated. METHODS: A total of 552 patients were randomized to evaluate whether the addition of POC to standard adjuvant treatment significantly improved outcome. Patients were stratified according to menopausal status, with 362 patients in the postmenopausal group and 192 patients in the premenopausal group. Premenopausal women with positive axillary nodes, negative hormonal receptors, or grade 3 tumors received adjuvant mitoxantrone-based chemotherapy. Node-negative premenopausal patients with grade 1 or 2 tumors expressing hormonal receptors received no standard adjuvant treatment. All postmenopausal women received hormonal therapy (tamoxifen 20 mg/day for 3 years). The perioperative regimen was a 14 mg/m(2) mitoxantrone infusion at the end of tumor excision. RESULTS: With a median follow-up of 6.1 years, this study showed no significant advantage of POC on overall survival, disease-free survival, or metastasis-free survival for the total cohort or for the premenopausal and postmenopausal groups. CONCLUSIONS: POC was a safe procedure in this study. However, the addition of POC to standard adjuvant treatment offered no benefit in breast cancer adjuvant treatment.