Composite breast reconstruction: Implant-based breast reconstruction with adjunctive lipofilling.

INTRODUCTION: Options for breast reconstructions enclose autologous tissue transfers or implants. Fat grafting is gaining more interest in this specific field of breast surgery. This study concentrates on the technique and aesthetic results of breast reconstruction with fat grafts combined with implants, in women who have undergone total mastectomy. METHODS: Breast reconstructions (n = 23) was performed using a protocol of intratissular expansion with serial deflation-lipofilling. In order to achieve the best aesthetic outcome, an additional small implant was placed. A retrospective data analysis was performed. In all patients a tissue expander was placed at the time of mastectomy or after removal of a previous breast reconstruction. The mean of lipoaspirate material for the reconstruction was 333 mL (range 120-715 mL). To create an adequate volume of the reconstructed breast, a supplementary small implant was placed, with a mean volume of 222 mL (range 125-375 mL). The mean follow-up was 33 months (range 19-50 months). RESULTS: A MRI analysis was performed in eight patients at least 9 months after the last lipofilling procedure, demonstrating a mean of 171 mL (range 64-538 mL) of transferred fat, a mean fat survival of 53% and a volume ratio of fat graft/implant of 0.97 (range 0,3-3,8). CONCLUSION: This composite technique of using autologous fat tissue and implants shows aesthetic pleasant results and must be considered as a valid alternative in a subset of patients. Further investigations to optimize the fat graft take must be encouraged.

Mesonephric adenocarcinoma of the cervix: Case report and literature review.

A mesonephric adenocarcinoma of the cervix is a very rare tumor deriving from remnants of the mesonephric duct. Differential diagnosis from other cervical carcinomas is difficult and little is known regarding its biological behavior, prognosis, and the optimal management strategy. We present a case of a mesonephric adenocarcinoma of the cervix with a comprehensive review of the existing literature. In this case a 66-year-old woman presented with postmenopausal vaginal bleeding. She was diagnosed with a FIGO stage IIB mesonephric adenocarcinoma of the cervix and treated with neoadjuvant chemoradiotherapy and a Wertheim hysterectomy. The recovery from surgery was uneventful and the patient remains with no evidence of disease with 2 years of follow-up.

Improving systemic breast cancer therapy: time to look beyond the primary tumour?

AIM: Intra and inter tumour heterogeneity is a known feature in cancer because tumour cells undergo changes at genetic and epigenetic level as they spread from their primary tumour site. Adjuvant treatment protocols in breast cancer are currently based on the biological characteristics of the primary tumour, which in most cases has been removed surgically. Considering tumour heterogeneity in metastases we examined the present status of knowledge regarding measurable differences in tumour profiling between the primary breast tumour and its synchronous axillary lymph node metastases (ALNM) and if so whether adjuvant therapy directed towards the tumour characteristics of the ALNM instead of those of the primary tumour is more effective. METHODS: We performed a literature search in Pubmed with the following MeSH headings: HUMAN and BREAST NEOPLASMS and RECEPTORS and ErbB-2. RESULTS: A significant change in tumour features was seen in metachronous metastases. In contrast, a high concordance of biomarker expression was reported between a primary breast tumour and its synchronous ALNM. CONCLUSION: Tumour heterogeneity is a challenge for targeted therapy. A poor response can be explained by the diversity of tumour cells. The biological profile of synchronous ALNM measured by oestrogen (ER), progesterone (PR) and her-2-neu receptor status does not differ from the primary breast tumour and is not predictive of the tumour profile in metachronous metastasis. New techniques, such as profiling of circulating tumour cells or tumour behaviour in xenografts, are promising in directing more effective adjuvant therapy.

Prone left-sided whole-breast irradiation: significant heart dose reduction using end-inspiratory versus end-expiratory gating.

PURPOSE: To quantify the influence on heart dose metrics of prone left-sided whole-breast irradiation in an end-inspiratory phase (PrIN) versus an end-expiratory phase (PrEX). PATIENTS AND METHODS: Twenty patients underwent CT-simulation in PrIN and PrEX. Dynamic intensity-modulated radiotherapy was planned for whole-breast irradiation with a median prescription dose of 40.05Gy in 15 fractions and maximal sparing of the organs at risk. Dose-volume parameters were analyzed for heart, left anterior descending coronary artery, ipsilateral lung and both breasts. RESULTS: PrIN consistently reduced (P<0.001) heart and left anterior descending coronary artery dose metrics compared to PrEX. Population averages for maximum and mean heart dose were 6.2Gy and 1.3Gy for PrIN versus 21.4Gy and 2.5Gy for PrEX, respectively. Moreover, a maximum heart dose less than 10Gy was achieved in 80% of patients for PrIN. Target dose distribution, ipsilateral lung and contralateral breast sparing by radiation dose were similar for both procedures. CONCLUSIONS: Inspiratory gating consistently reduced heart dose metrics pointing to a possible benefit of breathing-adapted radiotherapy for prone left-sided whole-breast irradiation.

Leiomyomatosis peritonealis disseminata associated with ascites and endometriosis: a case report and review of the literature.

We present a case of leiomyomatosis peritonealis disseminata (LPD) and review the literature. LPD is a rare, benign disorder that is characterized by multiple subperitoneal or peritoneal nodules of varying sizes on the omentum and peritoneal surfaces, grossly resembling disseminated carcinoma. It should be differentiated from other peritoneal tumors. It is mostly asymptomatic and diagnosis is often incidental during surgery. One should be aware of the iatrogenic component of this entity. LPD is being documented with increasing frequency. We report the case of a 39-year-old woman with chronic abdominal pain and heavy dysmenorrhea due to endometriosis associated with LPD. She underwent an abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy. LPD and endometriosis is a known association. LPD with ascites and endometriosis however has not yet been reported.

Improved cone-beam computed tomography in supine and prone breast radiotherapy. Surface reconstruction, radiation exposure, and clinical workflow.

BACKGROUND AND PURPOSE: Cone-beam computerized tomography (CBCT) enables three-dimensional information of the scanned region and provides soft tissue images with good spatial resolution. Our aim was to optimize image acquisition settings for prone and supine breast radiotherapy with respect to contour accuracy, clinical practicalities, and radiation dose. PATIENTS AND METHODS: CBCT images were acquired for both prone and supine anthropomorphic phantoms and a female cadaver in supine and prone set-up. CBCT protocols were investigated by altering the tube current, exposure time, range of projection views, field of view (FOV), and starting angle. For clinical practicalities, the frequency of the use of an offset CBCT isocenter was evaluated at 558 205°-CBCTs (37 patients; 13 prone and 24 supine) and 1272 360°-CBCTs (102 patients; 13 prone and 89 supine). RESULTS: Prone and supine breast CBCT images acquired with a bowtie filter, a small FOV, a range of projection views equaling 180°, a tube current of 20 mA and an exposure time of 32 ms, demonstrated adequate contour accuracy and an elimination of the offset CBCT isocenter procedure, while this occurred in 40.7 % for the old full-rotation protocol. Furthermore a 4.3-fold dose reduction was observed for the Computed Tomography Dose Index (CTDIw) compared to the preset Chest M20 protocol. CONCLUSION: The established 180° protocol demonstrated acceptable contour accuracy, eliminated the CBCT isocenter offset procedure and reduced patient radiation exposure.

Systematic review of breast cancer related lymphoedema: making a balanced decision to perform an axillary clearance.

AIM: Breast cancer-related lymphoedema (BCRL) is a disabling complication developing after breast cancer treatment in a proportion of patients. Its impact on quality of life becomes more substantial as survival after breast cancer diagnosis increases. The incidence of BCRL following breast cancer treatment varies due to a lack of -uniform definition and measurement criteria. This review aims to determine the prevalence of BCRL following axillary lymph node dissection (ALND) as a benchmark to be used in a risk-benefit medical decision whether to proceed with ALND or not. The risk of leaving unresected non-sentinel metastatic lymph nodes with a presumed inherent risk of local recurrence will be balanced against the risk of BCRL following a potentially unnecessary ALND. METHODS: Pubmed and Embase databases were searched for all publications on BCRL in order to estimate its -incidence and to decide on the most appropriate measurement method to use in clinical practice. RESULTS: 51 articles were identified on BCRL incidence and measurement technique. Most studies measured BCRL based on differences in arm circumference (n = 18) or by self-reported symptoms (n = 18). The weighted average of BCRL incidence following ALND measured by self-report and circumference method was 28% and 16%, respectively. CONCLUSION: The importance of ALND and irradiation as part of the treatment of operable breast carcinoma is well established, but its morbidity is less well documented. We argue self-report as the most appropriate method to -establish a diagnosis of BCRL. Therefore a 28% risk of finding non-sentinel lymph node metastases in a completion ALND will be regarded as the cut-off in a medical decision to proceed with ALND.

Intensity-modulated arc therapy with cisplatin as neo-adjuvant treatment for primary irresectable cervical cancer. Toxicity, tumour response and outcome.

PURPOSE: The goal of this work was to evaluate the feasibility and outcome of intensity-modulated arc therapy ± cisplatin (IMAT ± C) followed by hysterectomy for locally advanced cervical cancer. PATIENTS AND METHODS: A total of 30 patients were included in the study. The primary tumour and PET-positive lymph node(s) received a simultaneous integrated boost. Four weeks after IMAT ± C treatment, response was evaluated. Resection consisted of hysterectomy with or without lymphadenectomy. Tumour response, acute and late radiation toxicity, postoperative morbidity and outcome were evaluated. RESULTS: All hysterectomy specimens were macroscopically tumour-free with negative resection margins; pathological complete response was 40%. In 2 patients, one resected lymph node was positive. There was no excess in postoperative morbidity. Apart from two grade 3 hematologic toxicities, no grade 3 or 4 acute radiation toxicity was observed. No grade 3, 1 grade 4 (4%) intestinal, and 4 grade 3 (14%) urinary late toxicities were observed. The 2-year local and regional control rates were 96% and 100%, respectively. The 2-year distant control rate was 92%. Actuarial 2-year progression free survival rate was 89%. Actuarial 1- and 2-year overall survival rates were 96% and 91%, while 3-year overall survival was 84%. CONCLUSION: Surgery after IMAT ± C is feasible with low postoperative morbidity and radiation toxicity. Local, regional, distant control and survival rates are promising.

Xenotransplantation of cryopreserved human ovarian tissue into murine back muscle.

BACKGROUND: Ovarian tissue (OT) cryopreservation and transplantation are options for fertility preservation in young female cancer patients. METHODS: We investigated xenotransplantation of human OT into back muscle (B) of severe combined immunodeficiency mice. OT follicle content was evaluated by stereomicroscopy and pre-transplantation. Xenograft survival, follicular development (with/without FSH administration), apoptosis and vascularization were compared in B- versus K-site (under the kidney capsule) several times after grafting using histology, immunohistochemistry and magnetic resonance imaging. In vitro maturation (IVM) was also performed. RESULTS: Anastomoses which developed from existing human and invading murine vessels were seen in OT at both sites, but angiogenesis was more prominent at the B- than K-site (P < 0.001). Vascularization and follicle size were correlated in the B-group (Spearman's coefficient 0.73; P < 0.001). FSH increased early (8 days) micro-vessel formation in B but not in K grafts (P < 0.0001, versus no FSH). B-site grafts showed a better histological morphology and survival (P = 0.0084), formation of larger antral follicles (P = 0.005), more metaphase-II (MII) oocytes, growing follicles (P = 0.028) and slightly fewer apoptotic follicles than K grafts. One MI oocyte from B underwent IVM and reached MII stage next day. CONCLUSIONS: To our knowledge, this is the first report of MII and IVM-MII oocytes obtained from B xenografts. We report the largest oval-shaped antral follicles containing an MII oocyte obtained after OT xenotransplantation to date. Xenografting in the mouse B should be further explored as a method for human OT transplantation.

Mammography and breast sonography in transsexual women.

Data on the necessity of performing screening mammographies in transsexual women are lacking. The main objective of this study was to assess the possibility to perform mammography and breast sonography in transsexual women. Fifty Dutch-speaking transsexual women were interviewed about the following: attitude towards mammography and breast sonography, importance attributed to and satisfaction with breast appearance, opinion about the necessity of breast check-up, expectations regarding discomfort during the exams and knowledge about the breast surgery. A fasting blood sample, clinical breast exam, mammography and breast sonography were performed. At mammography the following parameters were noted: density, technical quality, location of the prostheses, presence of any abnormalities and painfulness. At sonography the following parameters were recorded: density, presence of cysts, visualisation of retro-areolar ducts or any abnormalities. Twenty-three percent of patients are not aware of the type of breast implants and 79% do not know their position to the pectoral muscles. Patient satisfaction with the appearance of their breasts was rather high (7.94 on a scale of 0-10). Mean expected and experienced pain from mammography was low (4.37 and 2.00 respectively). There was no statistically significant difference in expected pain between those who already had mammography and those who did not. There was a significant positive correlation between the expected and the experienced pain. Mammography and breast sonography were technically feasible and no gross anomalies were detected. Since both exams were judged as nearly painless, 98% of transsexual women intended to come back if they would be invited. Since breast cancer risk in transsexual women is largely unknown and breast exams are very well accepted, breast screening habits in this population should not differ from those of biological women.

Back muscle as a promising site for ovarian tissue transplantation, an animal model.

BACKGROUND: The aim of this study was to evaluate the optimal transplantation site for ovarian tissue fragments in murine hosts. We compared the transplantation to the back muscle (B) versus the kidney capsule (K) in a mouse allograft model. METHODS: Hemi-ovaries from 12-day-old mice were allografted into B and K of bilaterally ovariectomized same strain recipients which had undergone gonadotrophin stimulation (n = 15). Graft survival after 27 days, angiogenesis and follicle development were scored and compared to age-matched control ovaries (38-day old, n = 5). The ability of oocytes to be fertilized was studied after IVF, ICSI and embryos were transferred to recipient mothers. Anti-mouse CD 31+ antibody was used to evaluate neo-vascularization in grafts. RESULTS: Primordial follicle survival was higher (P < 0.01) and vascular support was better (P < 0.01) in B- than in K-grafts. From 34 oocytes retrieved from B-grafts (15 metaphase I, of which 14 matured in vitro, and 19 collected at metaphase II), 18 morulae were obtained. Transfer of 12 embryos obtained by ICSI led to three live offspring, and transfer of six IVF embryos to another recipient mother yielded four offspring, one of which was born dead and one showed placental anomalies. CONCLUSIONS: The back muscle is a promising site for ovarian allografts in mice. This is the first report of live offspring obtained after back muscle grafting using both IVF and ICSI.

Preceding sentinel node biopsy in early breast cancer: does it affect the number of axillary lymph nodes?

In the staging of early breast cancer a positive sentinel node biopsy is followed by axillary dissection in order to assess the number of metastasised lymph nodes. Immediate axillary dissection has been abandoned in our centre. If necessary, an axillary dissection takes place about two weeks later, but the post surgical inflammatory reaction might hinder dissection and decrease the number of removed lymph nodes. In a retrospective study, the total number of lymph nodes removed by sentinel node biopsy followed later by axillary dissection (n = 53) was compared with the total number of lymph nodes removed by axillary dissection without previous sentinel node biopsy in combination with breast conserving therapy (n = 113), or following breast conserving therapy (n = 15), or in combination with mastectomy (n = 65). A total number of 12 (median) lymph nodes were removed by sentinel node biopsy followed later by axillary dissection. Only in the mastectomy + axillary dissection group were less lymph nodes (median of 9) removed (P = 0.009). Multiple regression showed the total number of axillary lymph nodes to be correlated with age (R = -0.21; P = 0.002) and with the number of lymph nodes with metastasis (R = 0.31; P < 0.0001). Age distribution showed that the mastectomy + axillary dissection group had the oldest patient population. The number of removed axillary lymph nodes is not decreased by preceding sentinel node biopsy, but depends on other factors.

Two novel techniques to detect follicles in human ovarian cortical tissue.

BACKGROUND: Ovarian tissue cryopreservation and transplantation are becoming increasingly important issues for preserving female fertility as shown by recent successes in restoring ovarian activity and even fertility. Primordial follicle content before transplantation is a key issue for success. We investigated two novel methods to detect primordial follicles in human ovarian cortical tissue strips. METHODS: The first method used the fluorescent mitochondrial stain rhodamine 123 in combination with laser scanning confocal microscopy (LSCM). The first method used the fluorescent mitochondrial stain rhodamine 123 (R123) in combination with laser scanning confocal microscopy (LSCM). The second used a simple stereomicroscopic method with glass-bottom dishes for detecting primordial follicles in ovarian cortical tissue strips. Potential toxic effects of R123 and of the exposure to confocal laser were investigated in a mouse ovarian allograft model. RESULTS: Follicles were visible as white spots in thin cortical strips using LSCM in single and fast scanning at low magnification, allowing a fair estimation of the number of primordial follicles present. Using the second method, ovarian follicles were also visible using glass-bottom dishes under the stereomicroscope, although tissue thickness and density were limiting factors of its success. DISCUSSION: Follicles can be visualized in human cortical ovarian strips with R123 in combination with LSCM. Stereomicroscopy using glass-bottom dishes and transmitted illumination is a simple alternative method and has the advantage of allowing further safe clinical use of the analysed tissue.

Primary lymphoma of the cervix uteri: a diagnostic challenge. Report of two cases and review of the literature.

BACKGROUND: Primary non Hodgkin's lymphoma (NHL) of the cervix and vagina is uncommon; the incidence of uterine lymphoma is estimated to be less than 0.5% of all NHL. Patients regularly present with vaginal bleeding. The diagnosis is made on biopsy but this can be difficult on small samples which may not be representative of the lesion. Immunohistochemical analysis and often molecular techniques are required to confirm the diagnosis. CASES: We report two cases of primary diffuse large B-cell lymphoma of the cervix. In the first case, the diagnosis could only be made on repeat biopsies. The second case presented as a cervical polyp. CONCLUSION: Gynecologists should be aware of this rare clinical entity in order to apply the proper treatment.

Adenoid cystic carcinoma of the breast in a 19-year-old girl.

A case of adenoid cystic carcinoma of the breast in a 19-year-old girl is presented. As this tumor has specific characteristics and diagnostic criteria, this case illustrates the importance of an accurate histological diagnosis.

Follicular growth in fresh and cryopreserved human ovarian cortical grafts transplanted to immunodeficient mice.

OBJECTIVE: To investigate follicle growth in fresh and cryopreserved human ovarian cortical grafts transplanted to immunodeficient mice. STUDY DESIGN: Fresh or frozen-thawed human ovarian cortex was grafted subcutaneously or under the kidney capsule of 43 mice (35 nude mice and eight SCID mice), 14 of which were non-stimulated controls, 21 injected intra-peritoneally with gonadotrophins during 2 weeks and eight injected during 3 months. Follicle count was compared by Chi-square. RESULTS: Proportions of primordial follicles were significantly lower in grafts than in the tissue before transplantation in gonadotrophin-stimulated mice (37% versus 79%), but not in non-stimulated mice (51% versus 74%). Proportions of primary and secondary follicles were increased after transplantation indicating early follicular growth. One antral follicle was observed in a graft in a mouse stimulated for 3 months. CONCLUSION: Primordial follicles in fresh or frozen-thawed human ovarian cortex transplanted under the kidney capsule or subcutaneously can grow and are responsive to hormonal stimulation. CONDENSATION: Primordial follicles in fresh and cryopreserved human ovarian cortical grafts can initiate growth after transplantation to immunodeficient mice

Comparison of closed-loop controlled administration of propofol using Bispectral Index as the controlled variable versus "standard practice" controlled administration.

BACKGROUND: This report describes a new closed-loop control system for propofol that uses the Bispectral Index (BIS) as the controlled variable in a patient-individualized, adaptive, model-based control system, and compares this system with manually controlled administration of propofol using hemodynamic and somatic changes to guide anesthesia. METHODS: Twenty female patients, American Society of Anesthesiologists physical status I or II, who were scheduled for gynecologic laparotomy were included to receive propofolremifentanil anesthesia. In group I, propofol was titrated using a BIS-guided, model-based, closed-loop system. The BIS target was set at 50. In group II, propofol was titrated using classical hemodynamic signs of (in)adequate anesthesia. Performance of control during induction and maintenance of anesthesia were compared between both groups using BIS as the controlled variable in group I and the reference variable in group II, and, conversely, the systolic blood pressure as the controlled variable in group II and the reference variable in group I. At the end of anesthesia, recovery profiles between groups were compared. RESULTS: Although patients undergoing manual induction of anesthesia in group II at 300 ml/h reached a BIS level of 50 faster than patients undergoing open-loop, computer-controlled induction in group I, manual induction caused a more pronounced initial overshoot of the BIS target. This resulted in a more pronounced decrease in blood pressure in group II. During the maintenance phase, better control of BIS and systolic blood pressure was found in group I compared with group II. Recovery was faster in group I. CONCLUSION: A closed-loop system for propofol administration using the BIS as a controlled variable together with a model-based controller is clinically acceptable during general anesthesia.

Live offspring by in vitro fertilization of oocytes from cryopreserved primordial mouse follicles after sequential in vivo transplantation and in vitro maturation.

The objectives of the present study were to achieve 1) oocyte maturation, 2) oocyte competence of fertilization, and 3) oocyte competence of embryogenesis with oocytes from primordial follicles obtained from cryopreserved newborn mouse ovaries by using a two-step method. In the first step, frozen-thawed newborn mouse ovaries were transplanted under the kidney capsule of recipients for the initiation of growth from the primordial follicle stage on. In the second step, growing preantral follicles in the ovarian grafts were recovered and cultured. The results demonstrated that primordial follicles were able to be recruited to preantral follicles during the period of transplantation, and preantral follicles could be mechanically isolated from ovarian grafts. Under the present in vitro culture conditions, 85.8% of the isolated follicles (n = 332) from ovarian grafts survived the 12-day in vitro culture process, 84.9% of the recovered oocytes (n = 285) were germinal vesicle breakdown (GVBD)-competent, and 76% of the oocytes that underwent GVBD (n = 242) developed to the metaphase II (MII) stage. In the in vitro fertilization experiments, 75.4% of 142 inseminated MII oocytes underwent fertilization and cleavage to the 2-cell stage. Subsequently, 79.7% of the 2-cell-stage embryos (n = 69) progressed to the late morula-early blastocyst stage. Transfer of late morula-early blastocyst embryos resulted in the production of live offspring. From our experiments, it may be concluded that in vivo maturation by grafting followed by in vitro maturation of frozen-thawed primordial follicles can restore fertility in mice. This model could be useful for a similar application in the human.