Latissimus dorsi flap for breast reconstruction: a large single-institution evaluation of surgical outcome and complications.

PURPOSE: The use of autologous tissues is considered gold standard for patients undergoing breast reconstruction and is the preferred method in the post-radiation setting. Although the latissimus dorsi flap (LDF) has been replaced by abdominal flaps as technique of choice, it remains a valuable option in several specific clinical situations and its use has been regaining popularity in recent years. In this work, we present an 18-year retrospective analysis of a single-institution single-surgeon experience with LDF-based reconstruction with focus on early complications and reconstructive failures. METHODS: Hospital records of all patients undergoing breast surgery for any reason in the Certified Breast Cancer Center, Regio Klinikum Pinneberg, Germany between April, 1st 2005 and October, 31st 2022 were reviewed. 142 consecutive LDF-based reconstructive procedures were identified. Detailed information was gathered on patient characteristics, treatment-related factors, and complications. RESULTS: One hundred forty patients (139 female, 1 male) received 142 LDF-based surgeries. The flap was used mainly for immediate breast reconstruction with or without implant (83% of patients), followed by defect coverage after removal of a large tumor (7%), implant-to-flap conversion with or without placement of a new implant (6%), and delayed post-mastectomy reconstruction (4%). The use of LDF decreased between 2005 and 2020 (2005: 17, 2006: 13, 2007: 14, 2008: 16, 2009: 5, 2010: 9, 2011: 8, 2012: 3, 2013: 10, 2014: 8, 2015: 8, 2016: 7, 2017: 7, 2018: 4, 2019: 4, 2020: 2, 2021: 6, 2022: 4). Surgery was performed for invasive breast cancer in 78%, ductal carcinoma in situ in 20% and other reasons such as genetic mutation in 1% of patients. Ipsilateral radiation therapy was received by 12% of patients prior to LDF surgery and by 37% after the surgery. 25% of patients were smokers. The median duration of surgery, including all procedures conducted simultaneously such as e.g., mastectomy, axillary surgery, or implant placement, was 117 min (range 56-205). Patients stayed in the hospital for a median of 7 days (range 2-23 days). The most common complication was seroma (26%), followed by wound dehiscence (8%), surgical site infection (7%), partial skin and/or nipple necrosis of any size (7%) and hematoma requiring surgical evacuation (2%). 19% of all patients required seroma aspiration or drainage, mostly at the donor site and performed under ultrasound guidance in the ambulatory setting. Flap loss due to necrosis occurred in 2% of patients. CONCLUSIONS: Latissimus dorsi flap is a well-established surgical technique commonly used for immediate breast reconstruction as well as defect coverage in locally advanced breast cancer. To the best of our knowledge, this is one of the largest single-surgeon analyses of early complications in patients receiving LDF. As expected, seroma was the most common complication observed in nearly one third of patients and requiring a therapeutic intervention in every fifth patient. Serious adverse events occurred rarely, and flap loss rate was very low.

Intraoperative Ultrasound-Guided Excision of Non-Palpable and Palpable Breast Cancer: Systematic Review and Meta-Analysis.

Wire-guided localization (WGL) is the most frequently used localization technique in non-palpable breast cancer (BC). However, low negative margin rates, patient discomfort, and the possibility of wire dislocation have been discussed as potential disadvantages, and re-operation due to positive margins may increase relapse risk. Intraoperative ultrasound (IOUS)-guided excision allows direct visualization of the lesion and the resection volume and reduces positive margins in palpable and non-palpable tumors. We performed a systematic review on IOUS in breast cancer and 2 meta-analyses of randomized clinical trials (RCTs). In non-palpable BC, 3 RCTs have shown higher negative margin rates in the IOUS arm compared to WGL. Meta-analysis confirmed a significant difference between IOUS and WGL in terms of positive margins favoring IOUS (risk ratio 4.34, p < 0.0001, I2 = 0%). 41 cohort studies including 3291 patients were identified, of which most reported higher negative margin and lower re-operation rates if IOUS was used. In palpable BC, IOUS was compared to palpation-guided excision in 3 RCTs. Meta-analysis showed significantly higher rates of positive margins in the palpation arm (risk ratio 2.84, p = 0.0047, I2 = 0%). In 13 cohort studies including 942 patients with palpable BC, negative margin rates were higher if IOUS was used, and tissue volumes were higher in palpation-guided cohorts in most studies. IOUS is a safe noninvasive technique for the localization of sonographically visible tumors that significantly improves margin rates in palpable and non-palpable BC. Surgeons should be encouraged to acquire ultrasound skills and participate in breast ultrasound training.

Slow-freezing versus vitrification for human ovarian tissue cryopreservation.

PURPOSE: Ovarian tissue can be cryopreserved prior to chemotherapy using either the slow-freezing or the vitrification method; however, the data on the equality of the procedures are still conflicting. In this study, a comparison of the cryo-damage of human ovarian tissue induced by either vitrification or slow-freezing was performed. METHODS: Ovarian tissue from 23 pre-menopausal patients was cryopreserved with either slow-freezing or vitrification. After thawing/warming, the tissue was histologically and immunohistochemically analyzed and cultured in vitro. During tissue culture the estradiol release was assessed. RESULTS: No significant difference was found in the proportion of high-quality follicles after thawing/warming in the slow-freezing and vitrification group, respectively (72.7 versus 66.7 %, p = 0.733). Estradiol secretion by the ovarian tissue was similar between groups during 18 days in vitro culture (area-under-the-curve 5,411 versus 13,102, p = 0.11). Addition of Sphingosine-1-Phosphate or Activin A to the culture medium did not alter estradiol release in both groups. The proportion of Activated Caspase-3 or 'Proliferating-Cell-Nuclear-Antigen' positive follicles at the end of the culture period was similar between slow-freezing and vitrification. CONCLUSION(S): Slow-freezing and vitrification result in similar morphological integrity after cryopreservation, a similar estradiol release in culture, and similar rates of follicular proliferation and apoptosis after culture.

Protein profiling of genomic instability in endometrial cancer.

DNA aneuploidy has been identified as a prognostic factor in the majority of epithelial malignancies. We aimed at identifying ploidy-associated protein expression in endometrial cancer of different prognostic subgroups. Comparison of gel electrophoresis-based protein expression patterns between normal endometrium (n = 5), diploid (n = 7), and aneuploid (n = 7) endometrial carcinoma detected 121 ploidy-associated protein forms, 42 differentially expressed between normal endometrium and diploid endometrioid carcinomas, 37 between diploid and aneuploid endometrioid carcinomas, and 41 between diploid endometrioid and aneuploid uterine papillary serous cancer. Proteins were identified by mass spectrometry and evaluated by Ingenuity Pathway Analysis. Targets were confirmed by liquid chromatography/mass spectrometry. Mass spectrometry identified 41 distinct polypeptides and pathway analysis resulted in high-ranked networks with vimentin and Nf-κB as central nodes. These results identify ploidy-associated protein expression differences that overrule histopathology-associated expression differences and emphasize particular protein networks in genomic stability of endometrial cancer.

Genomic instability influences the transcriptome and proteome in endometrial cancer subtypes.

BACKGROUND: In addition to clinical characteristics, DNA aneuploidy has been identified as a prognostic factor in epithelial malignancies in general and in endometrial cancers in particular. We mapped ploidy-associated chromosomal aberrations and identified corresponding gene and protein expression changes in endometrial cancers of different prognostic subgroups. METHODS: DNA image cytometry classified 25 endometrioid cancers to be either diploid (n = 16) or aneuploid (n = 9), and all uterine papillary serous cancers (UPSC) to be aneuploid (n = 8). All samples were subjected to comparative genomic hybridization and gene expression profiling. Identified genes were subjected to Ingenuity pathway analysis (IPA) and were correlated to protein expression changes. RESULTS: Comparative genomic hybridization revealed ploidy-associated specific, recurrent genomic imbalances. Gene expression analysis identified 54 genes between diploid and aneuploid endometrioid carcinomas, 39 genes between aneuploid endometrioid cancer and UPSC, and 76 genes between diploid endometrioid and aneuploid UPSC to be differentially expressed. Protein profiling identified AKR7A2 and ANXA2 to show translational alterations consistent with the transcriptional changes. The majority of differentially expressed genes and proteins belonged to identical molecular functions, foremost Cancer, Cell Death, and Cellular Assembly and Organization. CONCLUSIONS: We conclude that the grade of genomic instability rather than the histopathological subtype correlates with specific gene and protein expression changes. The identified genes and proteins might be useful as molecular targets for improved diagnostic and therapeutic intervention and merit prospective validation.

Polar body biopsy in the diagnosis of monogenic diseases: the birth of three healthy children.

BACKGROUND: For prospective parents at risk of transmitting a monogenic disease, polar body analysis is an option for pre-conception genetic diagnosis. In Germany, polar body analysis is currently performed in only two centers (Lübeck and Regensburg). METHODS: The authors present a clinical series of 9 couples at risk for the transmission of a monogenic disease who underwent in vitro fertilization with polar body analysis. RESULTS: Nine couples have undergone in vitro fertilization with polar body analysis at the center in Lübeck since 2004. Three healthy children were born after polar body analysis for mucopolysaccharidosis type I, incontinentia pigmenti, and cystic fibrosis. The decision to undergo in vitro fertilization with polar body analysis is not easy for prospective parents to take, even though it often follows years of emotional suffering. Treatment with the methods of reproductive medicine in general, and with polar body analysis in particular, can cause considerable physical and emotional stress. CONCLUSIONS: For prospective parents in Germany at risk of transmitting a monogenic disease, polar body-based preimplantation diagnosis is an alternative to prenatal diagnosis and possible termination of pregnancy. The live birth rate per treatment cycle in this clinical series was 30%, which can be considered satisfactory. Nonetheless, most of the couples who did not achieve pregnancy after a first treatment cycle dropped out of treatment prematurely and did not go on to a second cycle.

The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome.

Recently, expression profiling of breast carcinomas has revealed gene signatures that predict clinical outcome, and discerned prognostically relevant breast cancer subtypes. Measurement of the degree of genomic instability provides a very similar stratification of prognostic groups. We therefore hypothesized that these features are linked. We used gene expression profiling of 48 breast cancer specimens that profoundly differed in their degree of genomic instability and identified a set of 12 genes that defines the 2 groups. The biological and prognostic significance of this gene set was established through survival prediction in published datasets from patients with breast cancer. Of note, the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets, such as luminal A and B, basal, normal-like, and ERBB2+, and prognostic signatures including MammaPrint and Oncotype DX, predicted genomic instability in our samples. This remarkable congruence suggests a biological interdependence of poor-prognosis gene signatures, breast cancer subtypes, genomic instability, and clinical outcome.