Ovarian carcinoma is the most lethal gynecologic malignancy because of its late diagnosis, extremely high recurrence rate, and limited curative treatment options. In clinical practice, high-grade serous carcinoma (HGSC) predominates due to its frequency, high aggressiveness, and rapid development of drug resistance. Recent evidence suggests that CXCL12 is an important immunological factor in ovarian cancer progression. Therefore, we investigated the predictive and prognostic significance of the expression of this chemokine in tumor and immune cells in patients with HGSC. We studied a cohort of 47 primary high-grade serous ovarian carcinomas and their associated recurrences. A tissue microarray was constructed to evaluate the CXCL12 immunostained tumor tissue. CXCL12 expression was evaluated and statistically analyzed to correlate clinicopathologic data, overall survival, and recurrence-free survival. A high proportion of CXCL12 + positive immune cells in primary ovarian serous carcinoma correlated significantly with chemosensitivity (p = 0.005), overall survival (p = 0.021), and longer recurrence-free survival (p = 0.038). In recurrent disease, high expression of CXCL12 was also correlated with better overall survival (p = 0.040). Univariate and multivariate analysis revealed that high CXCL12 + tumor-infiltrating immune cells (TICs) (HR 0.99, p = 0.042, HR 0.99, p = 0.023, respectively) and combined CXCL12 + /CD66b + infiltration (HR 0.15, p = 0.001, HR 0.13, p = 0.001, respectively) are independent favorable predictive markers for recurrence-free survival. A high density of CXCL12 + TICs predicts a good response to chemotherapy, leading to a better overall survival and a longer recurrence-free interval. Moreover, with concomitant high CXCL12/CD66b TIC density, it is an independent favorable predictor of recurrence-free survival in patients with ovarian carcinoma.

Abstract Objective Fascin and MAP17 are two well-known stem cell markers that have been previously shown to be associated with aggresive clinical features in cancer. This study aimed to assess their expression patterns and clinical significance in colorectal cancer. Methods Immunohistochemistry was used to assess the expression of fascin-1 and MAP17 in 111 specimens from patients with primary resectable colorectal cancer. Results were correlated with clinicopathological characteristics and survival data. Results Fascin-1 and MAP17 expression levels were associated with progressive anatomic disease extent (p=0.005), higher T classification (p=0.033), lymph node metastasis (p=0.002), high grade tumors (p=0.002), and vascular invasion (p=0.021). All patients with combined high fascin-1 and MAP17 expression died within 46 months after surgery, whereas patients with low fascin-1 and MAP17 expression had an excellent 5-year overall survival rate of 92.8% (95% CI: 83–98). Concerning 3-year PFS, only 14.3% (95%CI: 11–30) of patients with combined high expression of both biomarkers did not experience recurrence or death within 30 months of surgery. Conclusion Conclusions; Combined high expression of fascin-1 and MAP17 identifies a group of patiens with poor early overall survival, indicating therefore targeted therapy's necessity.

Increasing attention has been given to postoperative gastrointestinal functional outcome and quality of life after sigmoid resection for diverticulitis. Conversely, very little has been described about postoperative urogenital functional outcome and even less about its potential relationship to the type of vascular approach. The aim of this study was to evaluate whether central ligation of the inferior mesenteric artery (IMA) compared with peripheral dissection could impair urinary and sexual function in the long term. Patients undergoing elective laparoscopic sigmoid resection for diverticulitis from 2004 to 2017 were retrospectively analysed. They were asked to complete the American Urological Association Symptom Index (AUASI) questionnaire. Men received the five-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Patients were then divided according to the type of vascular resection. A response rate of the 36.4% to the AUASI and 43.8% to the IIEF-5 questionnaires was achieved. Three hundred and twenty four patients with a mean age of 62 ± 9.85 years were analysed for their urinary function (IMA preserved n  = 217; IMA resected n  = 107) in a median follow-up of 87 months. Furthermore, 115 men with a mean age of 60 ± 8.97 years were investigated for their sexual function (IMA preserved n  = 80; IMA resected n  = 35) in a median follow-up of 89 months. No difference (AUASI: 8 ± 6.32 IMA preserved vs. 7 ± 6.26 IMA resected, P  = 0.204; IIEF-5: 15 ± 7.67 IMA preserved vs. 15 ± 8.61 IMA resected, P  = 0.674) was found regarding the type of vascular approach during sigmoid resection. No association was found between the type of vascular approach and the long-term urogenital functional outcome in patients undergoing sigmoid resection for diverticulitis.

Background: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. Patients and Methods: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. Results: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056–0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049–0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. Conclusions: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

Increasing attention has been given to postoperative gastrointestinal functional outcome and quality of life after sigmoid resection for diverticulitis. Conversely, very little has been described about postoperative urogenital functional outcome and even less about its potential relationship to the type of vascular approach. The aim of this study was to evaluate whether central ligation of the inferior mesenteric artery (IMA) compared with peripheral dissection could impair urinary and sexual function in the long term.

Colorectal cancer continues to be the third most common cancer and constitutes the second leading cause of cancer-associated death among adults in the western societies. Despite the improvement of multimodality treatment with surgical resection and chemo-radiation, disease recurrence either as local recurrence or metastatic disease represents a major cause of significant cancer-associated morbidity and mortality in colorectal cancer. We previously reported that the solitary expression of either fascin-1 or MAP17 in colorectal cancer is associated with aggressive clinicopathological characteristics. The aim of the present study was to assess the clinical significance of the combined expression of both markers in colorectal cancer in terms of survival. A total of 111 patients with primary resectable colorectal cancer were examined for the expression of MAP17 and fascin-1 via immunohistochemistry. According to the cut-off points that were previously defined in our studies three groups of patients were compared; 1.) patients with combined low expression of fascin-1 and MAP17 (less than 10% staining within cancer cells for both markers) 2.) patients with combined high expression of fascin-1 and MAP17 (patients with fascin-1 expression more than 35% and expression of MAP17 more than 30% within cancer cells) 3.) all other patients were defined as displaying moderate expression of fascin-1 and MAP17. Results were correlated with clinicopathological characteristics as well as survival data. Progression-free survival (PFS) and overall survival (OS) were defined as the primary outcomes of this study. 33.3% of the patients displayed low combined fascin-1 and MAP 17 expression, 56.8% moderate expression, and 9.9% high expression. Combined expression of fascin-1 and MAP17 was associated with advanced T stage (p=0.020), the presence of lymph node (p < 0.001) and distant metastasis (p=0.001), higher grade of cellular differentiation (p=0.007), and the presence of vascular invasion (p=0.001). Interestingly, all patients with combined high expression of fascin-1 and MAP17 died within 46 months after surgery and only a 14.3% of the patients did not experience the event of recurrence or death in the first 30 months after surgery. On the contrary, patients with low expression of fascin-1 and MAP17 demonstrated an excellent 5-year progression-free survival and a 5-year overall survival up to 88.9%. Combined high expression of fascin-1 and MAP17 in patients with colorectal cancer identifies patients with aggressive tumor profiles. These two markers could be utilized in order to identify patients at risk for early death or as potential therapeutic targets.

Abstract Objective Colorectal cancer (CRC) remains the third most common cause of death from malignancies, while 30% of all these tumors develop in the rectum. The proximity of the rectum to vital structures, and in some cases the use of neoadjuvant treatment, make the surgical resection of this tumor a great challenge even for highly qualified surgeons. Understanding the mechanisms of rectal cancer (RC) development could lead to new concepts in the approach of diagnosis, prognosis, and eventually treatment of this disease. Despite the fact that TNM classification represents the gold standard tool for the staging of RC, a significant number of studies has recently focused on the association between the tumor microenvironment and RC. CD34 is a transmembrane phosphoglycoprotein expressed on human hematopoietic progenitor and vascular endothelial cells, as well in malignant tissues. It has also been shown to be involved in tumor invasion and angiogenesis. Because of the controversial data , we examined the expression of CD34 protein in RC specimens after stratifying the patients according to their UICC stage. Methods In our retrospective study, we included 364 patients with unselected, clinically annotated primary RC specimens. We analyzed a tissue microarray (TMA) of these specimens by immunohistochemistry (IHC) for the expression of CD34 protein by tumor cells. Results After stratifying the patients in nodal negative and positive groups, we found that the patients with Stage IIA tumors and high expression of CD34 protein had a favorable 5-year overall survival rate (53%; 95%CI = 40.0 – 65.1%) compared to tumors without expression of CD34 protein (26%; 95%CI = 10.7 – 44.6%, p = 0.003). Univariate and multivariate Hazard Cox regression survival analysis revealed that the combined the expression of CD34 protein was an independent, favorable, prognostic marker for overall survival in the stage IIA RC (HR = 0.39, 95%CI = 0.19 – 0.79; p = 0.009). Conclusion Our data show that the expression of CD34 protein represents an independent, favorable, prognostic condition in nodal negative stage IIA RC. Thereby, we provide novel insights into the prognostic role of the tumor microenvironment in RC that might help in the development of novel treatment modalities by its modification.

Nestin, a class VI intermediate filament protein of the cytoskeleton, and CD34, a transmembrane phosphoglycoprotein, are markers of progenitor cells. This study aimed to evaluate their expression and clinical significance in colorectal cancer. A clinically annotated tissue microarray, including 599 patients with colorectal cancer, was analyzed by immunohistochemistry. Furthermore, nestin and CD34 correlations with HIF-1a and a panel of cytokines and chemokines were assessed using quantitative reverse transcription PCR and The Cancer Genome Atlas dataset. Expression of nestin and CD34 was observed only in the tumor stroma. Patients displaying high expression of nestin and CD34 demonstrated higher rates of T1 and T2 tumors (p = .020), lower vascular invasion (p r = 0.37–0.78, p Combined expression of nestin and CD34 expression is associated with better overall survival possibly by modulating a favorable immune response.

Background: Various breast cancer reconstruction methods and novel surgical techniques include autologous or allogenic procedures, which can increase patient's quality of life and provide options when dealing with patients seen as challenging clinical scenarios. Summary: Our aim was to review the current literature and present published evidence on innovative standards in whole breast reconstruction. Advances in flap monitoring or newly published data regarding neurotization in breast reconstruction, arm lymphedema management, breast implant-associated anaplastic large cell lymphoma reconstruction treatment, and robotic surgery with regard to radiotherapy define innovative standards in the breast reconstruction setting. The role of meshes/acellular dermal matrix and fat grafting as well as optimal sequencing of postmastectomy radiotherapy in autologous and alloplastic breast reconstruction appear highly debatable also in expert panel meetings rendering further clinical research including RCTs imperative. Key Messages: There is an abundance of novel available techniques, which mandate further standardization, facilitating scientific evaluation in an attempt to help surgeons select tailored procedures for each patient with the goal to promote informed decision-making in breast reconstruction.

Background: Despite improvements in therapy of colorectal cancer, some patients will present occurrence of recurrence either locally or distantly. Tumor metastasis constitutes the major cause of cancer-associated morbidity and mortality. Nectin-1 belongs to the family of immunoglobulin-like cell adhesion molecules that contribute to the formation of cell-cell adhesions and regulate a series of cellular activities including cell polarization, differentiation, movement, proliferation, and survival. Expression of Nectin-1 in malignant tumors has been associated with aggressive tumor phenotypes. Objectives: The aim of the present study was to assess Nectin-1 expression patterns in colorectal cancer and to investigate its clinical significance. Methods: Nectin-1 expression was assessed via immunohistochemistry in surgical specimens of a cohort comprised of 111 patients with primary resectable colorectal cancer. Results were correlated with clinicopathological characteristics and survival data. Pro-gression-free survival was defined as the primary outcome of the present study. Results: Nectin-1 was strongly expressed in the cytoplasm of colorectal cancer cells. High Nectin-1 expression was associated with advanced stage of disease (p = 0.012) and lymph node metastasis (p = 0.007). Progression-free survival of patients exhibiting high expression of Nectin-1 in the first 36 months after surgery was significantly worse compared to patients with low expression of Nectin-1 (55.7%, 95% CI = 47-70, vs. 82.1%, 95% CI = 69-93, p = 0.014) and independent of other clinicopathological characteristics (HR = 0.389, 95% CI = 0.156-0.972, p = 0.043). Conclusion: Nectin-1 expression in colorectal cancer is associated with a significantly worse 3-year progression-free survival identifying therefore a group of patients with high risk for early disease recurrence. (c) 2019 S. Karger AG, Basel

Introduction: Colorectal cancer continues to be the third most common cancer and constitutes the second leading cause of cancer-associated death among adults in western societies. Despite the improvement of multimodality treatment with surgical resection and chemoradiation, disease recurrence either as local recurrence or metastatic disease represents a major cause of significant cancer-associated morbidity and mortality in colorectal cancer. L1CAM is a stem cell marker and a cell adhesion molecule that can be classified as a member of the immunoglobulin superfamily of cell adhesion molecules (IgCAM). Its aberrant expression in several different types of human solid tumors has been associated with aggressive tumor phenotypes. The aim of the present study was to assess the expression patterns of L1CAM and its clinical significance in colorectal cancer. Methods: A total of 109 patients with primary resectable colorectal cancer were examined for L1CAM expression via immunohistochemistry. Results were correlated with clinicopathological characteristics as well as survival data. Progression-free survival (PFS) and overall survival (OS) were defined as the primary outcomes of this study. Results: L1CAM displayed strong cytoplasmic expression in the colorectal cancer cells. Patients exhibiting high L1CAM expression were associated with advanced disease stage (P < .001), higher T stage (P = .040), the presence of lymph node (P < .001) and distant metastasis (P = .011). No correlations of L1CAM expression were demonstrated with the grade of tumor (P = .647), the presence of vascular (P = .360) or perineural invasion (P = .272) as wells as the presence of mucinous histologic subtype (P = .717). Kaplan-Meier curves revealed a significantly worse 3-year progression-free survival (29.7% vs 87.1%, P < .001) as well worse 5-year overall survival (39.9% vs 87.7%, P < .001) for patients displaying high L1CAM expression. Cox proportional hazard models demonstrated high L1CAM expression, independently of other clinicopathological characteristics, as a prognostic marker of progression-free survival (HR 0.187; 95%CI, 0.075-0.467; P < .001) and overall survival (HR 0.187; 95%CI, 0.049-0.483; P = .001). In the present study, patients with early stage cancer only and high L1CAM expression (Stage I and II according to UICC classification) presented as well significantly worse 3-year progression-free (42.9% vs 91.2%, P = .003) and 5-year overall survival (47.6% vs 90%, P = .008). Conclusion: High L1CAM expression in patients with colorectal cancer is associated with metastatic disease and dismal prognosis even in patients with early-stage disease. L1CAM could either represent a potential target for the development of a tumor profiling test in order to identify patients at high risk for disease recurrence or could be utilized as a target for immunotherapy.

Background: Metastatic disease in colorectal cancer represents a major cause of significant cancer-associated morbidity and mortality. L1CAM is a stem cell marker, cell adhesion molecule, belongs to the immunoglobulin superfamily of cell adhesion molecules (IgCAM) and it is aberrantly expressed in several different types of human solid tumors. The aim of the present study was to assess the expression patterns of L1CAM and its clinical significance in colorectal cancer. Patients and methods: Surgical specimens of 109 patients with primary resectable colorectal cancer were examined for L1CAM expression via immunohistochemistry and the results were correlated with clinical and survival data. Results: L1CAM expression was significantly correlated with advanced stage of disease (p < .001), higher T classification (p = .040), the presence of lymph node (p < .001) and distant metastasis (p = .011). Patients displaying high L1CAM expression demonstrated a dismal three-year progression free survival (29.7% vs 87.1%, p < .001) and five-year overall survival (39.9% vs 87.7%, p < .001). Multivariate analysis using Cox proportional hazard models revealed high L1CAM expression as a prognostic marker of dismal progression free (HR 0.187, 95%CI = 0.075-0.467, p < .0001) and overall survival (HR 0.154, 95%CI = 0.049-0.483, p = .001) independent of other clinicopathological characteristics. Subgroup analysis comprised of patients with early stage disease only presented as well significantly worse progression free and overall survival when L1CAM exhibited high expression. Conclusions: Colorectal cancer patients displaying high expression of L1CAM harbor high risk for metastasis already in early stage disease identifying therefore a group of patients prone to dismal prognosis.

Breast cancer stem cells are considered to be a major cause of disease recurrence in breast cancer as they appear to be chemoresistant. Fascin-1 and MAP17 are stem cell markers whose excessive expression in tumors is associated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of fascin-1 and MAP17 in breast cancer and to assess their clinical significance. Expression of fascin-1 and MAP17 was assessed via immunohistochemistry in surgical specimens of a cohort comprised of 127 patients with resectable breast cancer. Results were correlated with clinicopathological characteristics and survival data. Progression-free survival (PFS) was defined as the primary outcome of the present study. Fascin-1 and MAP17 expression were strongly associated with the presence of triple-negative cancers (p < 0.0001). Tumors displaying high expression of fascin-1 presented correlations with high tumor grade (p = 0.002) and high expression of Ki-67 (p = 0.004). PFS of patients exhibiting high expression of fascin-1 and MAP17 in cancer cells in the first 5 years after surgery was significantly worse than in patients with low expression of the two markers (47.8%, 95% confidence interval [CI] 33–51 vs. 80.5%, 95% CI 47–56; p = 0.012) and independent of other clinicopathological characteristics (hazard ratio 0.171, 95% CI 0.034–0.869; p = 0.033). Combined expression of fascin-1 and MAP17 in breast cancer cells is associated with a significantly worse 5-year PFS, therefore recognizing a group of patients with high risk for early disease recurrence.

OBJECTIVE:The ideal location of specimen extraction in laparoscopic-assisted colorectal surgery is still debatable. The aim of this study was to compare the incidence of incisional hernias and surgical site infections in patients undergoing elective laparoscopic resection for recurrent sigmoid diverticulitis by performing specimen extraction through left lower transverse incision or Pfannenstiel-Kerr incision.METHODS:A total of 269 patients operated between January 2014 and December 2017 were retrospectively screened for inclusion in the study. Patients with specimen extraction through left lower transverse incision (LLT) and patients with specimen extraction through Pfannenstiel-K incision (P-K) were matched in 1:1 proportion regarding age, sex, comorbidities, and previous abdominal surgery. The incidence of incisional hernias and surgical site infections were compared by using Fisher's exact test.RESULTS:After matching 77 patients in the LLT group and 77 patients in the P-K group, they were found to be homogenous regarding the above mentioned descriptive characteristics. No patients in the P-K group developed an incisional hernia compared with 10 patients (13%) in the LLT group (p = 0.001). All these patients required hernia repair with mesh augmentation. The rate of surgical site infections was 1/77 in the P-K group and 0/77 in the LLT group (p = 1.0). In the P-K group, a wound protector was used in 86% of patients whereas in the LLT group, 39% of the wounds were protected during specimen extraction (p < 0.0001).CONCLUSION:The Pfannenstiel-Kerr incision may be the preferred extraction site compared with the left lower transverse incision given the significant reduction of the risk of incisional hernias.

BACKGROUND:Breast reconstruction is routinely used to alleviate the psychological adverse effects of mastectomy. Nipple preservation further improves the cosmetic result, and causes less trauma on the body surface. Nipple-sparing mastectomy, however, comes with challenges, especially in the case of large, ptotic breasts to the degree that large-sized breasts have conventionally been a contraindication for nipple preservation. In this report, we describe a novel technique for nipple preservation in immediate reconstruction of large, ptotic breasts. METHODS:From 2013 to 2018, 24 patients (30 breasts) with large, ptotic breasts were treated with mastectomy and immediate reconstruction with nipple preservation. Median BMI was 28 and 8 patients were smokers. The technique involves the de-epithelialisation of a large area of the breast skin, the mastectomy through a lateral full-thickness incision within the de-epithelialised area, imbrication of the de-epithelialised skin, lifting of the nipple to a higher position and finally closure of wound. RESULTS:There were no full, 4 partial nipple necroses and 3 re-operations were done under local anaesthetic to correct partial peripheral necrosis of the areola. Six patients needed seroma aspiration and 4 presented with cellulitis. No implants were lost and there were no delays to adjuvant treatment. CONCLUSIONS:The proposed technique has significant advantages and may be ideal when large skin reductions are necessary in immediate breast reconstruction with nipple preservation. The low complication rate makes the method ideal when adjuvant treatment is to follow and/or patients are of high risk for surgical complications.

Ekaterini Christina Tampaki, Athanasios Tampakis, Raoul Droeser, Efstratios Patsouris, and Gregory Kouraklis B Department of Propaedeutic Surgery, Laikon General Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; National Organization for the Provision of Healthcare Services, Department of Planning and Monitoring of Medicines Dispensing, Medicines Division, Greece; Department of General and Visceral Surgery, University Hospital of Basel, Switzerland; Institute for Surgical Research and Hospital Management ICFS, Basel, Switzerland; A Department of Pathology, Laiko General Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece