Factors predicting in-breast tumor recurrence after breast-conserving surgery

Purpose: The main objectives of this study were to identify risk factors for local in-breast tumor recurrence after breast-conservation and to evaluate the impact of IBTR (in-breast tumor recurrence) on overall survival. Methods: A total of 335 consecutive patients with 346 invasive and insitu breast cancers were treated with breast conserving therapy. Univariate and multivariate statistical analysis were performed and survival rates were calculated and analyzed using the Kaplan-Meier method. Results: With a median follow-up period of 70.6months 14 patients (4%) developed an IBTR. Overall survival and the disease-free 8-year actuarial survival of patients were 95% and 93%, respectively. The overall survival of patients with tumour recurrence on any site was significantly shorter than of those without recurrence (64% versus 85% after 8years of follow-up; P<0.0001). Similarly, overall survival was significantly reduced in patients with distant metastases compared to all others without distant disease (88% versus 40% after 8years; P<0.0001). In contrast, overall survival of patients who experienced IBTR did not differ significantly from the group of patients who never developed IBTR (87% versus 70% after 8years of follow-up). By univariate analysis, lobular carcinoma, high grade tumours, multifocality, concomitant LCIS and DCIS, the absence of estrogene and progesterone receptor status, as well as R1-status, were significant predictors of IBTR. By multivariate analysis, only R1-status (P<0.002) and the presence of LCIS around the invasive tumour (P<0.03) remained as significant factors predicting IBTR. Conclusions: Concomitant lobular carcinomas insitu, as well as R1 surgical status are independent significant risk factors for in breast tumor recurrence after breast conserving therap

The single-cell pathology landscape of breast cancer.

Single-cell analyses have revealed extensive heterogeneity between and within human tumours1-4, but complex single-cell phenotypes and their spatial context are not at present reflected in the histological stratification that is the foundation of many clinical decisions. Here we use imaging mass cytometry5 to simultaneously quantify 35 biomarkers, resulting in 720 high-dimensional pathology images of tumour tissue from 352 patients with breast cancer, with long-term survival data available for 281 patients. Spatially resolved, single-cell analysis identified the phenotypes of tumour and stromal single cells, their organization and their heterogeneity, and enabled the cellular architecture of breast cancer tissue to be characterized on the basis of cellular composition and tissue organization. Our analysis reveals multicellular features of the tumour microenvironment and novel subgroups of breast cancer that are associated with distinct clinical outcomes. Thus, spatially resolved, single-cell analysis can characterize intratumour phenotypic heterogeneity in a disease-relevant manner, with the potential to inform patient-specific diagnosis

Pregnancy at early age is associated with a reduction of progesterone-responsive cells and epithelial Wnt signaling in human breast tissue

Pregnancy at early age is the most significant modifiable factor which consistently decreases lifetime breast cancer risk. However, the underlying mechanisms haven't been conclusively identified. Studies in mice suggest a reduction in progesterone-receptor (PR) sensitive epithelial cells as well as a downregulation of the Wnt signaling pathway as being one of the main mechanisms for the protective effect of early pregnancy. The aim of our study was to validate these findings in humans.; We collected benign breast tissue of 125 women who had been stratified according to age at first pregnancy and the occurrence of subsequent breast cancer, and performed immunohistochemistry for PR, Wnt4 and the Wnt-target Versican.; The number of PR positive epithelial cells was significantly lower in the group of women with early pregnancy and no subsequent breast cancer compared to the group of nulliparous women with subsequent invasive breast cancer (p = 0.0135). In women with early pregnancy, expression of Versican and Wnt4 was significantly lower compared to nulliparous women (p = 0.0036 and p = 0.0241 respectively), and Versican expression was also significant lower compared to women with late pregnancy (p &lt; 0.0001).; Our results confirm prior observations in mice and suggest a role of downregulation of epithelial Wnt signaling in the protective effect of early pregnancy in humans. This results in a decreased proliferation of stem/progenitor cells; therefore, the Wnt signaling pathway may represent a potential target for breast cancer prevention in humans

Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

Purpose Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. Methods The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. Results Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. Conclusions In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques

Factors predicting in-breast tumor recurrence after breast-conserving surgery

PURPOSE: The main objectives of this study were to identify risk factors for local in-breast tumor recurrence after breast-conservation and to evaluate the impact of IBTR (in-breast tumor recurrence) on overall survival. METHODS: A total of 335 consecutive patients with 346 invasive and in situ breast cancers were treated with breast conserving therapy. Univariate and multivariate statistical analysis were performed and survival rates were calculated and analyzed using the Kaplan-Meier method. RESULTS: With a median follow-up period of 70.6 months 14 patients (4%) developed an IBTR. Overall survival and the disease-free 8-year actuarial survival of patients were 95% and 93%, respectively. The overall survival of patients with tumour recurrence on any site was significantly shorter than of those without recurrence (64% versus 85% after 8 years of follow-up; P > 0.0001). Similarly, overall survival was significantly reduced in patients with distant metastases compared to all others without distant disease (88% versus 40% after 8 years; P > 0.0001). In contrast, overall survival of patients who experienced IBTR did not differ significantly from the group of patients who never developed IBTR (87% versus 70% after 8 years of follow-up). By univariate analysis, lobular carcinoma, high grade tumours, multifocality, concomitant LCIS and DCIS, the absence of estrogene and progesterone receptor status, as well as R1-status, were significant predictors of IBTR. By multivariate analysis, only R1-status (P > 0.002) and the presence of LCIS around the invasive tumour (P > 0.03) remained as significant factors predicting IBTR. CONCLUSIONS: Concomitant lobular carcinomas in situ, as well as R1 surgical status are independent significant risk factors for in breast tumor recurrence after breast conserving therapy

Symptomatic giant peritoneal loose body in the pelvic cavity: A case report

Introduction: Giant peritoneal loose bodies (gPLB) occur rarely and therefore only few have been described. Often they are found incidentally and have no clinical relevance, whereas symptomatic forms may require surgical removal. Presentation of case: We report the case of a male patient suffering from abdominal discomfort with alternating localizations for several years, actually presenting with a proctitis. With elevated inflammatory markers, a conspicuous resistance in the lower abdomen and in order to evaluate further affection of the colon, an abdominal CT-scan was performed. It revealed a spherical mass in the lesser pelvis. A colonoscopy confirmed the proctitis, showing no further pathologies. Due to the symptoms and the uncertain entity of the mass, a diagnostic laparoscopy was performed and a boiled egg-like structure (diameter 5.2 cm) was removed. The patient recovered well and was free of symptoms. Discussion: The patient had two potential reasons for his symptoms, one of them being a suspected leftover foreign body years after an appendectomy. The proctitis was treated conservatively but without complete remission of the abdominal discomfort. Therefore, a diagnostic laparoscopy was performed and the mass turned out to be a gPLB. Conclusion: To obtain a fast diagnosis and to perform an adequate conservative or surgical therapy, the knowledge about the rare entity of a gPLB is necessary. An exact anamnesis, clinical examination and the knowledge about the diagnostic values of radiological and endoscopic investigations are crucial

Large ovarian cystadenofibroma causing large bowel obstruction in a patient with Klippel–Feil syndrome—A case report

AbstractIntroductionOvarian cystadenofibromas (CAF) are epithelial tumors, which are fairly rare, mainly benign and asymptomatic. The Klippel–Feil syndrome (KFS) is a rare congenital anomaly which combines osseous and visceral development disorders. While bowel obstruction is a common complication in advanced ovarian cancer this condition is rarely described in cystic lesions such as CAF. We report the first case of large bowel obstruction due to a large benign ovarian CAF with an underlying KFS.Presentation of caseA 60-year-old women with a KFS was admitted to the hospital with increasing abdominal girth and bowel obstruction. A CT scan revealed a massive intraabdominal cystic tumor of unclear origin, causing compression of the sigmoid colon with consecutive dilatation of the ascending colon and the small bowel. After successful conservative ileus treatment including nasogastric tube and iv fluids for a few days, we performed an explorative laparotomy, revealing a large cystic tumor originating from the left adnexe. After its removal including left adnexectomy, histological findings confirmed a benign cystadenofibroma. The hospital stay was uneventful and bowel obstruction symptoms resolved immediately.DiscussionBeside careful history taking and physical examination, diagnostic imaging is important to identify CAF. However, the distinction between benign and malignant lesions remains difficult even using MRI. Considering optimal preparation of the patient with successful ileus treatment, laparoscopy may have been the surgical approach of choice. Though, direct laparotomy seemed to be the appropriate approach, considering the unclear origin and dignity of the lesion. Considering the KFS and its inherent malformations interdisciplinary cooperation seems important in such rare cases.ConclusionPreoperative MR imaging and intraoperative frozen-sections can be helpful to determine the dignity of the neoplasm and avoid fertility impairing adnexectomy in young woman. Interdisciplinary management of such rare conditions seems of utmost importance

The role of preoperative blood parameters to predict the risk of surgical site infection

Routine preoperative blood work is not recommended but selected biochemical markers may predict the risk of surgical site infection (SSI). This study examines the association between preoperative biochemical markers and the risk of SSI.; This observational cohort study, nested in a randomized controlled trial, was conducted at two tertiary referral centers in Switzerland.; 122 (5.8%) of 2093 patients experienced SSI. Preoperative increasing levels of albumin (OR 0.93), CRP (OR 1.34), hemoglobin (OR 0.87) and eGFR (OR 0.90) were significantly associated with the odds of SSI. The same accounts for categorized parameters. The highest area under the curve from ROC curves was 0.62 for albumin. Positive predictive values ranged from 6.4% to 9.5% and negative predictive values from 94.8% to 95.7%. The association of CRP, mildly and moderately decreased eGFR and hemoglobin with the odds of SSI remained significant on multivariate analysis.; Our results do not support generally delaying elective surgery based on preoperative blood results. However, it may be considered in situations with potentially severe sequelae of SSI