Daniele Friedman

Pregnancies in an 18-Year Follow-up after Biliopancreatic Diversion

Background: 239 pregnancies occurred in 1136 women who had undergone biliopancreatic diversion (BPD). Methods: There were 73 abortions, and 14 pregnancies are presently in their course. The 152 term pregnancies (six twins) occurred in 129 women 2-173 months (mean 42.7) after BPD. Mean age and current excess weight were 31.4 years (20-42) and 29.1% (-6.9-78.2), and mean excess weight loss was 72.9% (30.4-110.5). Results: Mean weight gain during pregnancy was 6.2 kg (-21-25). In 32 patients (21%), parenteral nutritional support was needed. In all the other patients (79%), the usual supplementations were given. Of the newborns, 122 were delivered at term (84.7%) with a mean weight of 2842.4 g (1760-4600 g) and a mean length of 48.5 cm (43-59 cm), while the 22 preterm babies (15.3%) weighed 2151.1 g (1400-3850 g) and had a length of 44.6 cm (33-56 cm). Forty infants (27.8%) were small for gestational age but 17 of them weighed more than 2500 g. Eleven twins (one abortion at 26th week) were also delivered, with a mean weight of 2088.6 g (1200-3100 g) and a mean length of 45.6 cm (35-50 cm). Delivery was spontaneous in 85 instances (56%), while vacuum extractor was used in one, and 66 cesarean sections were performed. There were two birth malformations, one infant died after surgery for meconium obstruction and two died from unknown causes. Of the 129 women, 35 had been infertile before BPD. Conclusions: Disappearance of infertility and decrease of pregnancy risk are to be considered among the beneficial effects of weight reduction following BPD.

Lymphedema Microsurgical Preventive Healing Approach: A New Technique for Primary Prevention of Arm Lymphedema After Mastectomy

BackgroundThe purpose of this manuscript is to assess the efficacy of direct lymphaticvenous microsurgery in the prevention of lymphedema following axillary dissection for breast cancer.MethodsNineteen patients with operable breast cancer requiring an axillary dissection underwent surgery, carrying out LVA between the blue lymphatics and an axillary vein branch simultaneously. The follow-up after 6 and 12 months from the operation included circumferential measurements in all cases and lymphangioscintigraphy only in 18 patients out of 19 cases.ResultsBlue nodes in relation to lymphatic arm drainage were identified in 18/19 patients. All blue nodes were resected and 2-4 main afferent lymphatics from the arm could be prepared and used for anastomoses. Lymphatic-venous anastomoses allowed to prevent lymphedema in all cases. Lymphangioscintigraphy demonstrated the patency of microvascular anastomoses.ConclusionsDisruption of the blue nodes and closure of arm lymphatics can explain the significantly high risk of lymphedema after axillary dissection. LVA proved to be a safe procedure for patients in order to prevent arm lymphedema.

Atypical Ductal Hyperplasia Diagnosed at 11-Gauge Vacuum-Assisted Breast Biopsy Performed on Suspicious Clustered Microcalcifications: Could Patients Without Residual Microcalcifications Be Managed Conservatively?

OBJECTIVE The purpose of our study was to establish whether it might be safe for women with a diagnosis of atypical ductal hyperplasia (ADH) at stereotactically guided vacuum-assisted breast biopsy without any residual microcalcification after the procedure to undergo mammographic follow-up instead of surgical biopsy. MATERIALS AND METHODS From October 2003 to January 2009, 1173 consecutive 11-gauge vacuum-assisted breast biopsy procedures were performed. ADH was found in the specimens of 114 patients who underwent vacuum-assisted breast biopsy for a single cluster of suspicious microcalcifications smaller than 15 mm; 49 had residual microcalcifications, and 65 had microcalcifications completely removed by the procedure. Of 49 patients with residual microcalcifications, 41 underwent surgical biopsy. Of 65 patients without residual microcalcifications, 26 underwent surgical biopsy, 35 were not surgically treated and were managed conservatively with mammographic follow-up, and 4 had follow-up of less than 24 months. RESULTS In 41 patients with residual microcalcifications who underwent surgical biopsy, 8 malignant lesions were found at surgery. The underestimation rate was 20% (8/41). In 26 patients without residual microcalcifications who underwent surgical biopsy, no malignant lesions were found. One malignant lesion was found in the 35 patients managed conservatively at follow-up. The underestimation rate in patients without residual microcalcifications using surgical biopsy or mammographic follow-up as the reference standard was 1.6% (1/61). CONCLUSION Patients without residual microcalcifications after vacuum-assisted breast biopsy could possibly be managed in a conservative way with mammographic follow-up.

The use of bioelectrical impedance analysis for monitoring body composition changes during nutritional support

Body composition was measuredwith bioelectric impedance analysis (BIA) in 30 patients with protein malnutrition following biliopancreatic diversion. Determinations were carried out prior to, during, and at the completion of intravenous nutritional support when the nutritional parameters had completely reverted to normal. Before treatment, body weight (BW), lean body mass (LBM), and body fat (BF) values were similar to those of controls, whereas the total body sodium/total body potassium (TBNa/TBK) and extracellular mass/body cell mass (ECM/BCM) ratios were considerably higher. During the support, no changes in BW, LBM, and BF were demonstrated, although a sharp decrease of TBNa/TBK and ECM/BCM was observed, thus demostrating improved LBM composition. At the end of parenteral feeding, the BW, LBM, and BF values were similar to those observed before the support, while a further decrease in TBNa/TBK and ECM/BCM demonstrated a recovery towards normal of body composition. The full correspondence between clinical and BIA findings therefore suggests that this method may be valuable for monitoring body composition changes during nutritional support.

Orbital swelling as a first symptom in breast carcinoma diagnosis: a case report

IntroductionThe frequency of intra-orbital metastasis in systemic cancer is a controversial topic. Of all metastatic tumors to the orbit of the eye, breast carcinoma is considered to be the most prevalent. Orbital findings typically present themselves after the diagnosis of the primary tumor, with an average delay of three to six years. In spite of that, this study reports a case in which orbital manifestation was the initial symptom in breast carcinoma diagnosis.Case presentationA 66-year-old Italian Caucasian woman presented with a swelling located on the lower orbit of her right eye.ConclusionsPrevious cases report orbital manifestations discovered secondary to breast cancer. This case demonstrates that orbital symptoms may be the primary presentation of the disease. Orbital metastasis originating from breast cancer predicts widespread metastatic disease in other organs. In the presence of an ambiguous infiltrative orbital process, diagnostic examination of the breast is recommended.

Implant-based Breast Reconstruction Using a Polyester Mesh (surgimesh-pet): A Retrospective Single-center Study

Background: Although the introduction of acellular dermal matrices is considered one of the most important advancements in alloplastic breast reconstruction, costs and local policy limit their use in Italy. The purpose of this study was to assess short-term outcomes following Surgimesh-PET–based breast reconstruction. Methods: A single-center, retrospective, case-control study was performed from January 1, 2012, to December 31, 2013, by enrolling 206 breast reconstructions performed in 196 patients after oncologic (n = 200) or prophylactic (n = 6) mastectomy. Group A included 63 patients who underwent 70 immediate Surgimesh-PET–assisted breast reconstructions, and group B included 133 patients who underwent 136 standard breast reconstructions. Results: No significant differences between groups occurred for early postoperative complications (p = 0.610), major complications that required surgical revision (p = 0.887), volume (p = 0.498) or width of the prosthesis (p = 0.201), skin-sparing mastectomy (p = 0.315), or axillary surgery (p = 0.265). Multivariate logistic regression showed that prior radiotherapy was the only significant variable for early postoperative complications in both whole series (p = 0.011) and group B (p = 0.046), whereas body mass index greater than 25 was an independent predictor in group A (p = 0.041). Prior radiotherapy was the only variable that reached statistical significance in the multivariate model for major complications in the whole series (p = 0.005). Conclusions: Short-term outcomes of Surgimesh-PET–based alloplastic breast reconstruction are promising. Further studies are needed to evaluate the long-term results of this surgical approach. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Quantitative Real Time PCR assessment of hormonal receptors and HER2 status on fine-needle aspiration pre-operatory specimens from a prospectively accrued cohort of women with suspect breast malignant lesions

OBJECTIVES Reliable assessment of estrogen, progesterone (ER and PR), and HER2 receptor status are essential in breast cancer (BC) treatment. Immunohistochemical methods are limited by intra- and inter-laboratory variability. Furthermore, current methods are not the ideal approach for reproducing the biological continuum of ER, PR, and HER2 receptor levels, due to their intrinsic, semi-quantitative nature, relying in part on subjective interpretation. METHODS In the present study, we tested a molecular approach to define ER, PR, and HER2 status in fine-needle-aspirate (FNA) samples from patients with early BC. We performed flow cytometry analysis on 88 FNA specimens from suspect BC patients to determine cellularity. We used quantitative Real Time PCR (QRT-PCR) to assess ER, PR, HER2 status, and qPCR for HER2 gene copy number (GCN). RESULTS ER and PR mRNA levels showed a highly significant correlation with IHC data on surgical samples. qPCR showed greater accuracy than IHC in defining HER2 status. QRT-PCR defined better than IHC the continuous spectrum of the expression of the assessed receptors. Moreover, PCR analysis demonstrated a strict correlation between HER2 status and higher levels of its transcript, correctly stratifying HER2+ and HER2- patients. Finally, there was a strongly significant agreement between HER2 GCN assessed on FNA specimens by qPCR and FISH data obtained on pathological tissue specimens. CONCLUSIONS The present results support a comprehensive approach to determine ER, PR, and HER2 status by PCR (QRT-PCR and qPCR) in FNA specimens, with high relevance for therapeutic strategies like neoadjuvant treatment.

Dose-dense Vinorelbine and Paclitaxel with Granulocyte Colony-stimulating Factor in Metastatic Breast Cancer Patients: Anti-tumor Activity and Peripheral Blood Progenitor Cell Mobilization Capability

We studied the safety, activity and peripheral blood progenitor cell mobilizing capability of a dose-dense combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy for patients with metastatic breast cancer (MBC). Forty-three MBC patients were submitted to four cycles of VNB 30 mg/m2 and PTX 175 mg/m2 intravenously, every 2 weeks, as the first induction step of a tandem high-dose chemotherapy program. Granulocyte colony-stimulating factor (G-CSF) 5 µg/kg was administered daily from day +5 to +10 in order to accelerate hematopoietic recovery, or 48 h after the last VNB–PTX when a leukapheresis was planned (after the third or fourth cycle). A total of 172 cycles were administered. The mean delivered dose-intensity of VNB and PTX was 14.7 and 86 mg/m2/week, respectively (98% of the planned dose-intensity). The main per-patient toxicities were: peripheral neurotoxicity (G1/2 60%, G3 5%), constipation (G1/2 10%), oral mucositis (G1/2 20%), and asthenia (G1/2 35%). Hematological toxicity was unremarkable, except for anemia with hemoglobin (Hb) values <10 g/dl (28%), and lymphopenia with lymphocyte counts <1000/mm3 (28%). Two complete (5.1%) and 24 partial (61.5%) responses were observed in 39 assessable patients, for an overall response rate of 66.6% (95% CI 51.6–80.9). A median of one apheretic procedure (range 1–3) was required to achieve the target number of 6 × 106/kg CD34+ cells. The median number of CD34+ harvested per patient was 15 × 106/kg (range 6.4–36.5). Four cycles of dose dense VNB and PTX showed a favorable toxicity profile, a relevant anti-tumor activity and a high peripheral blood progenitor cell mobilizing activity.

Adjuvant intraoperative radiotherapy for selected breast cancers in previously irradiated women: Evidence for excellent feasibility and favorable outcomes

BACKGROUND The present report provides preliminary outcomes with intraoperative radiotherapy delivered to women with breast cancer included in a re-irradiation program. MATERIALS AND METHODS From October 2010 to April 2014, thirty women were included in a re-irradiation protocol by exploiting IORT technique. The median time between the two irradiations was 10 years (range 3-50). All patients underwent conservative surgery, sentinel lymph node excision and IORT with electron beam delivered by a mobile linear accelerator. Primary endpoint was esthetic result and consequential/late toxicity; secondary endpoints were local control (LC), disease free survival (DFS) and overall survival (OS). RESULTS With a median follow up of 47 months (range 10-78), we analyzed 29 patients (1 lost at follow up). Twenty-seven patients (90%) had presented breast cancer local relapse or a new primary cancer in the same breast after a previous conservative surgery plus radiation treatment; three patients (10%) had previously received irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts (21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC, DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively. CONCLUSION Although we analyzed a small number of patients, our results are satisfactory and this approach is feasible even if it could not be considered the standard treatment. Further clinical trials exploring IORT are needed to identify possible subgroups of patients that might be suitable for this type of approach.

Her2 assessment using quantitative reverse transcriptase polymerase chain reaction reliably identifies Her2 overexpression without amplification in breast cancer cases

BackgroundImmunohistochemistry (IHC) and fluorescent-in situ hybridization (FISH) are standard methods to assess human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) patients. Real-time quantitative polymerase-chain-reaction (qRT-PCR) is able to detect HER2 overexpression. Here we compared FISH, IHC, quantitative PCR (qPCR), and qRT-PCR to determine the concordance rates and evaluate their relative roles in HER2 determination.Patients and methodsWe determined HER2 status in 153 BC patients, using IHC, FISH, Q-PCR and qRT-PCR. In discordant cases, we directly measured HER2 protein levels using Western blotting.ResultsThe overall agreement (OA) between FISH and Q-PCR was 94.1, with a k value of 0.87. Assuming FISH as the standard reference, Q-PCR showed an 86.1% sensitivity and a 99.0% specificity with a global accuracy of 91.6%. OA between FISH and qRT-PCR was 90.8% with a k value of 0.81. Of interest, the disagreement between FISH and qRT-PCR was mostly restricted to equivocal cases. HER2 protein analysis suggested that qRT-PCR correlates better than FISH with HER2 protein levels, particularly where FISH fails to provide conclusive results.SignificanceqRT-PCR may outperform FISH in identifying patients overexpressing HER2 protein. Q-PCR cannot be used for HER2 status assessment, due to its suboptimal level of agreement with FISH. Both FISH and Q-PCR may be less accurate than qRT-PCR as surrogates of HER2 protein determination.