Controversies in the prophylactic mastectomy with simultaneous breast reconstruction

Catedra chirurgie nr. 1 “N. Anestiadi”, USMF „Nicolae Testemiţanu”; Institutul Oncologic, Chişinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Mastectomia profilactică (MP) întruneşte mai multe controverse, îndeosebi: valoarea MP pentru prevenirea cancerului mamar şi în ce măsură tratamentul medicamentos al mastopatiei poate reduce riscul de cancer mamar fără necesitatea MP. Material şi metode: MP s-a efectuat la 6 paciente cu vârsta între 25 şi 41 ani. Examinarea preoperatorie a inclus ultrasonografia, mamografia, CT, RMN (2 cazuri), citologia, testele genetice BRCA-1 şi BRCA-2. În 4 cazuri MP subcutanată s-a efectuat bilateral, iar în 2 cazuri – unilateral, pe fond de cancer mamar al glandei mamare contralaterale. Varianta de acces pentru MP în fiecare caz a fost individuală, în dependenţă de prezenţa şi sediul cicatricelor după rezecţiile mamare sectorale anterioare. Rezultate: În 5 cazuri operaţia s-a finisat cu reconstrucţia mamară cu implant. La 2 paciente s-a constatat o ischemie pronunţată a areolei şi mamelonului. Diminuarea sensibilităţii tegumentelor şi a complexului areolo-mamelonar s-a observat la toate pacientele. În perioada postoperatoare nu s-a înregistrat nici o extruzie a implantului, inflamaţie sau contractură mamară. Rezultatul estetic de reconstrucţie mamară în cazul MP “skin sparing” este superior comparativ cu reconstrucţia după mastectomia clasică. Concluzii: Considerăm determinante următoarele criterii pentru efectuarea MP: anamneza familiară agravată, cancerul suportat anterior la sînul contralateral, cancerul multicentric, multifocal, vârsta, factorul histologic, testele genetice pozitive BRCA-1 şi BRCA-2. Decizia în favoarea MP poate fi luată doar după o examinare minuţioasă şi în deplin acord cu pacienta.Introduction: Prophylactic mastectomy (PM) meets several controversies which are especially: the value of PM for preventing breast cancer and also the extent of the mastopathy drug therapy that may reduce the risk of breast cancer without requiring PM. Material and methods: PM was performed on 6 patients, aged between 25 and 41 years. Preoperative examination included ultrasound, mammography, CT, MRI (two cases), cytology, tests BRCA-1 and BRCA-2. Subcutaneous PM was performed bilaterally in 4 cases. In two cases of breast cancer PM was performed unilaterally for contralateral gland. Each case of PM had an individual type of incision depending on the presence and location of previous scars after the sectorial resection of the breast. Results: Simultaneous breast reconstruction was performed in 5 cases with implants. Two patients had a pronounced ischemia of areola and nipple. The decrease skin and areola sensitivity was observed in all cases. There has been no extrusion of the implant, and no breast inflammation or contracture in the postoperative period. The aesthetic result of breast reconstruction for PM via “skin sparing” mastectomy is superior to classical mastectomy. Conclusions: We consider defining the following criteria of PM – aggravated familiar history, previously supported contralateral cancer, multicenter and multifocal cancer, age of patient, histologic factor and positive BRCA-1 and BRCA-2 tests. The decision in favor of PM should be taken only after thorough examination and in full agreement with the patient

Optimization of results in breast reconstruction

Catedra de chirurgie nr. 1 „Nicolae Anestiadi”, Catedra de chirurgie nr.4, USMF „Nicolae Testemițanu”, Chișinău, Republica Moldova, Conferința stiințifică „Nicolae Anestiadi – nume etern al chirurgiei basarabene” consacrată centenarului de la nașterea profesorului Nicolae Anestiadi 26 august 2016Introducere. Cancerul mamar (CM) rămâne cea mai răspândită formă de tumoare malignă la femei. Mastectomia duce la un aspect inacceptabil pentru orice femeie și doar reconstrucția mamară (RM) poate izbăvi bolnava de un coşmar psihologic. Scopul. Perfectarea tehnicilor de reconstrucție mamară. Material și metode. RM a fost efectuata la 39 paciente cu vârsta cuprinsa intre 26 si 58 de ani. Operația de RM s-a efectuat prin metoda expander-implant la 19 paciente, doar cu aplicarea implantului mamar în 8 cazuri si în 12 cu lamboul TRAM (Transversus Rectus Abdominis Myocutaneous flap). Cu scop de adaptare a vascularizării lamboului și de prevenire a necrozelor marginale, inclusiv a necrozei adipoase în 5 cazuri cu o luna înainte de operația TRAM s-a efectuat ligaturarea a. epigastrice inferioare, iar în două cazuri s-au efectuat inciziile elipsoidale și s-a mobilizat lamboul TRAM, apoi s-a suturat pe același loc. În a doua etapă s-a efectuat transpoziția lamboului și s-a modelat glanda mamară. Rezultate. În aceste cazuri nu am întâlnit necroze marginale de lambou. Expanderul anatomic Eurosillicone cu valva integrată oferă posibilitatea modelării unei forme mai naturale a GM. Concluzii. Astfel, alegerea metodei de RM trebuie efectuată cu respectarea principiilor oncologice şi în dependenţă de starea regiunii recipiente. Efectuarea în două etape a operației de reconstrucție mamară cu lamboul TRAM poate diminua incidența necrozelor marginale.Introduction. Breast cancer remains the most common form of malignancy in women. Mastectomy lead to unacceptable look for any woman and only breast reconstruction (BR) can deliver a psychological nightmare. Purpose. The aim of the work was perfecting the techniques for breast reconstruction. Material and methods. BR was performed in 39 patients. Age range was between 26 and 58 years. BR operation was performed by the expander-implant method in 19 patients, implant application was made in 8 cases and TRAM flap (transversus rectus abdominis flap Myocutaneous) in 12 cases. Inferior epigastric artery ligation was performed one month before TRAM flap operation for vascularization adapting and for prevent of marginal necrosis, including fat necrosis in 5 cases. Mobilization of TRAM flap's, without rearrangement, was performed in two cases. In the second stage transposition flap was performed and was modeled mammary gland. Results. In these cases we encountered marginal flap necrosis. Eurosillicone integrated valve anatomical expander creates the possibility for modeling of more natural forms of mammary gland. Conclusion. Thus, choosing the method of BR must be made on oncologic principles and depending on the condition of receiver region. Making two-stage surgery for breast reconstruction with TRAM flap may reduce the incidence of marginal necrosis

Prophylactic mastectomy with immediate breast reconstruction

CME SANCOS, Catedra Chirurgie nr.4, Universitatea de Stat de Medicină și Farmacie „NicolaeTestemițanu”, Chșinău, Republica Moldova, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaIntroducere: Mastectomia profilactică (MP) poate reduce riscul de apariție a cancerului mamar cu 90-95% în majoritatea situațiilor. Cu toate acestea, sunt foarte importanți termenii de reconstrucție a sânilor și prezervarea complexului areolă-mamelon pentru satisfacția pacienților. Material și metode: Mastectomia profilactică a fost efectuată la 14 pacienți cu o vârstă medie de 38,3 (interval, 25-45 ani). Examenul preoperator a inclus ultrasonografie, mamografie, CT, RMN, citologie, teste genetice BRCA 1/2. MP bilaterală ”nipple-sparing” a fost realizat în 9 cazuri și unilateral (după cancer mamar controlateral) în 5 cazuri. Accesul chirurgical pentru MP a fost individual și a depins de prezența și localizarea cicatricilor postoperatorii după rezecțiile sectorale anterioare. Intervențiile chirurgicale au fost finalizate cu o reconstrucție mamară cu implant. Rezultate: O ischemie pronunțată de areolă și mamelon a fost determinată în 2 cazuri. Reducerea sensibilității pielii și a complexului areolă-mamelon (CAM) a fost observată la toate pacientele. Nu a survenit o extruzie a implantului, inflamație sau contractură capsulară în perioada postoperatorie. Rezultatul estetic de reconstrucție mamară în cazul MP “nipple-sparing” este superior comparativ cu reconstrucția după mastectomia clasică. Concluzii: Mastectomia profilactică este o bună opțiune pentru pacientele care prezintă un risc sporit de apariție a cancerului de sân. Reconstrucția mamară imediată cu implant și prezervarea CAM crește gradul de satisfacție postoperatorie a pacienților.Introduction: Prophylactic mastectomy (PM) can reduce the risk of developing breast cancer by 90-95% in most situations. However, the terms of the breast reconstruction and the preservation of the nipple-areolar complex (NAC) are very important for the patient satisfaction. Material and methods: Prophylactic mastectomy was performed on 14 patients with a mean age 38,3 (range, 25-45 years). Preoperative examination included ultrasonography, mammography, CT, NMR, cytology, genetic tests BRCA 1/2. A bilateral nipplesparing PM was accomplished in the 9 cases and unilateral (after contralateral breast cancer) in 5 cases. Surgical access for the PM was individual and depended of the presence and localization of the postoperative scars after the previous sectoral resections. The surgical interventions finished with an implant breast reconstruction. Results: A pronounced ischemia of areola and nipple was determined in 2 cases. The reduction in sensitivity of the skin and NAC has been observed in all patients. There was no implant extrusion, inflammation or capsular contracture in the postoperative period. The aesthetic result of mammary reconstruction in MP nipple-sparing is superior compared to reconstruction after classical mastectomy. Conclusions: Prophylactic mastectomy is a good option for patients who are at high risk of developing breast cancer. Immediate implant breast reconstruction and preservation of the NAC increase patient’s satisfaction

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies