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Int J Surg Oncol [JOURNAL]

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Management of rectal cancer and liver metastatic disease: which comes first?

Tsoulfas G, Pramateftakis MG

Int J Surg Oncol · 2012 · PMID 22778934 · Full text

In the last few decades there have been significant changes in the approach to rectal cancer management. A multimodality approach and advanced surgical techniques have led to an expansion of the treatment of metastatic d... In the last few decades there have been significant changes in the approach to rectal cancer management. A multimodality approach and advanced surgical techniques have led to an expansion of the treatment of metastatic disease, with improved survival. Hepatic metastases are present at one point or another in about 50% of patients with colorectal cancer, with surgical resection being the only chance for cure. As the use of multimodality treatment has allowed the tackling of more complicated cases, one of the main questions that remain unanswered is the management of patients with synchronous rectal cancer and hepatic metastatic lesions. The question is one of priority, with all possible options being explored. Specifically, these include the simultaneous rectal cancer and hepatic metastases resection, the rectal cancer followed by chemotherapy and then by the liver resection, and finally the "liver-first" option. This paper will review the three treatment options and attempt to dissect the indications for each. In addition, the role of laparoscopy in the synchronous resection of rectal cancer and hepatic metastases will be reviewed in order to identify future trends.

Total pelvic exenteration for gynecologic malignancies.

Diver EJ, Rauh-Hain JA, Del Carmen MG

Int J Surg Oncol · 2012 · PMID 22720150 · Full text

Total pelvic exenteration (PE) is a radical operation, involving en bloc resection of pelvic organs, including reproductive structures, bladder, and rectosigmoid. In gynecologic oncology, it is most commonly indicated fo... Total pelvic exenteration (PE) is a radical operation, involving en bloc resection of pelvic organs, including reproductive structures, bladder, and rectosigmoid. In gynecologic oncology, it is most commonly indicated for the treatment of advanced primary or locally recurrent cancer. Careful patient selection and counseling are of paramount importance when considering someone for PE. Part of the evaluation process includes comprehensive assessment to exclude unresectable or metastatic disease. PE can be curative for carefully selected patients with gynecologic cancers. Major complications can be seen in as many as 50% of patients undergoing PE, underscoring the need to carefully discuss risks and benefits of this procedure with patients considering exenterative surgery.

Surgical management of locally recurrent rectal cancer.

Hogan NM, Joyce MR

Int J Surg Oncol · 2012 · PMID 22701789 · Full text

Developments in chemotherapeutic strategies and surgical technique have led to improved loco regional control of rectal cancer and a decrease in recurrence rates over time. However, locally recurrent rectal cancer contin... Developments in chemotherapeutic strategies and surgical technique have led to improved loco regional control of rectal cancer and a decrease in recurrence rates over time. However, locally recurrent rectal cancer continues to present considerable technical challenges and results in significant morbidity and mortality. Surgery remains the only therapy with curative potential. Despite a hostile intra-operative environment, with meticulous pre-operative planning and judicious patient selection, safe surgery is feasible. The potential benefit of new techniques such as intra-operative radiotherapy and high intensity focussed ultrasonography has yet to be thoroughly investigated. The future lies in identification of predictors of recurrence, development of schematic clinical algorithms to allow standardised surgical technique and further research into genotyping platforms to allow individualisation of therapy. This review highlights important aspects of pre-operative planning, intra-operative tips and future strategies, focussing on a multimodal multidisciplinary approach.

Glove port technique for transanal endoscopic microsurgery.

Alessandro C, Daniela M, Michele M … +6 more , Andrea T, Gianmarco G, Massimo S, Orazio Z, Fabio G, Giuseppe T

Int J Surg Oncol · 2012 · PMID 22701788 · Full text

Introduction. Despite initial enthusiasm, the use of transanal endoscopic microsurgery (TEM) is still quite limited at present because of the expense of highly specialized equipment and the complexity of the learning cur... Introduction. Despite initial enthusiasm, the use of transanal endoscopic microsurgery (TEM) is still quite limited at present because of the expense of highly specialized equipment and the complexity of the learning curve. Furthermore, some authors report a relevant, although temporary, effect on anorectal function because of the considerable anal dilatation which can even produce a rupture of the internal anal sphincter. The "glove TEM" proposes itself as an alternative to traditional TEM that could settle these problems. Materials and Methods. The technique is accurately described together with the necessary equipment to perform it. Between 2011 and 2012, we operated eight patients with this technique for rectal adenomas or early carcinomas achieving R0 resection in all cases and reporting no early or late complications during the first five months of followup. Discussion. This technique offers multiple advantages compared to the original TEM. (i) It allows the use of all available laparoscopic instruments. (ii) It gives a great manoeuvrability of the instruments in contrast to rigid rectoscope systems. (iii) Given the limited length of the device, it permits to operate on tumors closer to the dentate line. (iv) It is less traumatic to the anal sphincter. It is definitively much cheaper. Conclusions. We believe that this new technique is easy to perform, cost-effective, and less traumatic to the anal sphincter compared to traditional TEM.

Intersphincteric resection and coloanal anastomosis in treatment of distal rectal cancer.

Cipe G, Muslumanoglu M, Yardimci E … +2 more , Memmi N, Aysan E

Int J Surg Oncol · 2012 · PMID 22690335 · Full text

In the treatment of distal rectal cancer, abdominoperineal resection is traditionally performed. However, the recognition of shorter safe distal resection line, intersphincteric resection technique has given a chance of... In the treatment of distal rectal cancer, abdominoperineal resection is traditionally performed. However, the recognition of shorter safe distal resection line, intersphincteric resection technique has given a chance of sphincter-saving surgery for patients with distal rectal cancer during last two decades and still is being performed as an alternative choice of abdominoperineal resection. The first aim of this study is to assess the morbidity, mortality, oncological, and functional outcomes of intersphincteric resection. The second aim is to compare outcomes of patients who underwent intersphincteric resection with the outcomes of patients who underwent abdominoperineal resection.

Memorial sloan-kettering cancer center: two decades of experience with ductal carcinoma in situ of the breast.

Choi DX, Van Zee KJ

Int J Surg Oncol · 2012 · PMID 22685640 · Full text

Researchers at Memorial Sloan-Kettering Cancer Center have investigated many aspects of their experience with ductal carcinoma in situ of the breast over the past 20 years. This paper summarizes the most clinically relev... Researchers at Memorial Sloan-Kettering Cancer Center have investigated many aspects of their experience with ductal carcinoma in situ of the breast over the past 20 years. This paper summarizes the most clinically relevant findings.

The significance of splenectomy for advanced proximal gastric cancer.

Nashimoto A, Yabusaki H, Matsuki A

Int J Surg Oncol · 2012 · PMID 22685639 · Full text

Objectives. The significance of splenectomy in advanced proximal gastric cancer is examined retrospectively. Methods. From 1994 to 2004, 505 patients with advanced proximal gastric cancer underwent curative total gastrec... Objectives. The significance of splenectomy in advanced proximal gastric cancer is examined retrospectively. Methods. From 1994 to 2004, 505 patients with advanced proximal gastric cancer underwent curative total gastrectomy with preserving spleen (T) for 264 patients and total gastrectomy with splenectomy (ST) for 241 patients. Results. Patients who underwent splenectomy showed more advanced lesions. The metastatic rate of lymph node (LN) in the splenic hilus (No. 10) in ST was 18.3%. As for the incidence of surgical complications, there was not statistically difference except for pancreatic fistula. The index of estimated benefit of (No. 10) LN was 4.2, which was similar to that of (No. 9), (No. 11p), (No. 11d), and (No. 16) LNs. 5-year survival rate of (No. 10) positive group was 22.2%. 5-year survival rates of pSE and pN2 in T group were better than that of pSE and pN2 in ST, respectively. The superiority of ST was not confirmed even in Stage II, IIIA, and IIIB. Conclusion. Splenectomy was not effective for patients with (No. 10) metastasis in long-term survival. Spleen-preserving total gastrectomy will be feasible and be enough to accomplish radical surgery for locally advanced proximal gastric cancer.

The current state of targeted agents in rectal cancer.

Kim DD, Eng C

Int J Surg Oncol · 2012 · PMID 22675625 · Full text

Targeted biologic agents have an established role in treating metastatic colorectal cancer (CRC), and the integration of targeted therapies into the treatment of CRC has resulted in significant improvements in outcomes.... Targeted biologic agents have an established role in treating metastatic colorectal cancer (CRC), and the integration of targeted therapies into the treatment of CRC has resulted in significant improvements in outcomes. Rapidly growing insight into the molecular biology of CRC, as well as recent developments in gene sequencing and molecular diagnostics, has led to high expectations for the identification of molecular markers to be used in personalized treatment regimens. The mechanisms of action and toxicities of targeted therapies differ from those of traditional cytotoxic chemotherapy. Targeted therapy has raised new insight about the possibility of tailoring treatment to an individual's disease, the assessment of drug effectiveness and toxicity, and the economics of cancer care. This paper covers the last decade of clinical trials that have explored the toxicity and efficacy of targeted agents in locally advanced and metastatic CRC and how their role may benefit patients with rectal cancer. Future efforts should include prospective studies of these agents in biomarker-defined subpopulations, as well as studies of novel agents that target angiogenesis, tumor-stromal interaction, and the cell signaling pathways implicated in rectal cancer.

Ductal carcinoma in situ: recent advances and future prospects.

Lambert K, Patani N, Mokbel K

Int J Surg Oncol · 2012 · PMID 22675624 · Full text

Introduction. This article reviews current management strategies for DCIS in the context of recent randomised trials, including the role of sentinel lymph node biopsy (SLNB), adjuvant radiotherapy (RT) and endocrine trea... Introduction. This article reviews current management strategies for DCIS in the context of recent randomised trials, including the role of sentinel lymph node biopsy (SLNB), adjuvant radiotherapy (RT) and endocrine treatment. Methods. Literature review facilitated by Medline, PubMed, Embase and Cochrane databases. Results. DCIS should be managed in the context of a multidisciplinary team. Local control depends upon clear surgical margins (at least 2 mm is generally acceptable). SLNB is not routine, but can be considered in patients undergoing mastectomy (Mx) with risk factors for occult invasion. RT following BCS significantly reduces local recurrence (LR), particularly in those at high-risk. There remains a lack of level-1 evidence supporting omission of adjuvant RT in selected low-risk cases. Large, multi-centric or recurrent lesions should be treated by Mx and immediate reconstruction should be discussed. Adjuvant hormonal treatment may reduce the risk of LR in selected cases with hormone sensitive disease. Conclusion. Further research is required to determine the role of new RT regimes and endocrine therapies. Biological profiling and molecular analysis represent an opportunity to improve our understanding of tumour biology in DCIS to rationalise treatment. Reliable identification of low-risk lesions could allow treatment to be less radical.

A Primer on the Current State-of-the-Science Neoadjuvant and Adjuvant Therapy for Patients with Locally Advanced Rectal Adenocarcinomas.

Yorio JT, Bhadkamkar NA, Kee BK … +1 more , Garrett CR

Int J Surg Oncol · 2012 · PMID 22666572 · Full text

Patients with rectal cancers, due to the unique location of the tumor, have a recurrence pattern distinct from colon cancers. Advances in adjuvant therapy over the last three decades have played an important role in impr... Patients with rectal cancers, due to the unique location of the tumor, have a recurrence pattern distinct from colon cancers. Advances in adjuvant therapy over the last three decades have played an important role in improving patient outcomes. This article serves to review the clinical studies that lay the basis for our current standard-of-care treatment of patients with locally advanced rectal cancer, as well as touch upon future ongoing experimental clinical trials of adjuvant chemoradiation therapy.

Investigational Paradigms in Downscoring and Upscoring DCIS: Surgical Management Review.

Orsaria P, Granai AV, Venditti D … +2 more , Petrella G, Buonomo O

Int J Surg Oncol · 2012 · PMID 22666571 · Full text

Counseling patients with DCIS in a rational manner can be extremely difficult when the range of treatment criteria results in diverse and confusing clinical recommendations. Surgeons need tools that quantify measurable p... Counseling patients with DCIS in a rational manner can be extremely difficult when the range of treatment criteria results in diverse and confusing clinical recommendations. Surgeons need tools that quantify measurable prognostic factors to be used in conjunction with clinical experience for the complex decision-making process. Combination of statistically significant tumor recurrence predictors and lesion parameters obtained after initial excision suggests that patients with DCIS can be stratified into specific subsets allowing a scientifically based discussion. The goal is to choose the treatment regimen that will significantly benefit each patient group without subjecting the patients to unnecessary risks. Exploring the effectiveness of complete excision may offer a starting place in a new way of reasoning and conceiving surgical modalities in terms of "downscoring" or "upscoring" patient risk, perhaps changing clinical approach. Reexcison may lower the specific subsets' score and improve local recurrence-free survival also by revealing a larger tumor size, a higher nuclear grade, or an involved margin and so suggesting the best management. It seems, that the key could be identifying significant relapse predictive factors, according to validated risk investigation models, whose value is modifiable by the surgical approach which avails of different diagnostic and therapeutic potentials to be optimal. Certainly DCIS clinical question cannot have a single curative mode due to heterogeneity of pathological lesions and histologic classification.

Radiotherapy after conservative surgery in ductal carcinoma in situ of the breast: a review.

Amichetti M, Vidali C

Int J Surg Oncol · 2012 · PMID 22655186 · Full text

Several large prospective and retrospective studies have demonstrated excellent long-term outcomes after breast conservative treatment with radiation in invasive breast cancer. Breast-conserving surgery (BCS) followed by... Several large prospective and retrospective studies have demonstrated excellent long-term outcomes after breast conservative treatment with radiation in invasive breast cancer. Breast-conserving surgery (BCS) followed by radiotherapy (RT) is an accepted management strategy for patients with DCIS. Adding radiation treatment after conservative surgery enables to reduce, without any significant risks, the rate of local recurrence (LR) by approximately 50% in retrospective and randomized clinical trials. As about 50% of LRs are invasive and have a negative psychological impact, minimizing recurrence is important. Local and local-regional recurrences after initial breast conservation treatment with radiation can be salvaged with high rates of survival and freedom from distant metastases.

No excess mortality in patients aged 50 years and older who received treatment for ductal carcinoma in situ of the breast.

Bastiaannet E, van de Water W, Westendorp RG … +4 more , Janssen-Heijnen ML, van de Velde CJ, de Craen AJ, Liefers GJ

Int J Surg Oncol · 2012 · PMID 22655185 · Full text

Background. The incidence of ductal carcinoma in situ (DCIS) has increased at a fast rate.The aim of this study was to assess the incidence and treatment in the Netherlands and estimate the excess mortality risk of DCIS.... Background. The incidence of ductal carcinoma in situ (DCIS) has increased at a fast rate.The aim of this study was to assess the incidence and treatment in the Netherlands and estimate the excess mortality risk of DCIS. Methods. From the Netherlands Cancer Registry, adult female patients (diagnosed 1997-2005) with DCIS were selected. Treatment was described according to age. Relative mortality at 10 years of follow-up was calculated by dividing observed mortality over expected mortality. Expected mortality was calculated using the matched Dutch general population. Results. Overall, 8421 patients were included in this study. For patients aged 50-64, and 65-74 an increase in breast-conserving surgery was observed over time (P < 0.001). For patients over 75 years of age, 8.0% did not undergo surgery; this percentage remained stable over time (P = 0.07). Overall, treated patients aged >50 years experienced no excess mortality regardless of treatment (relative mortality 1.0). Conclusion. The present population-based study of almost 8500 patients showed no excess mortality in surgically treated women over 50 years with DCIS.

Intraductal proliferative lesions of the breast-terminology and biology matter: premalignant lesions or preinvasive cancer?

Costarelli L, Campagna D, Mauri M … +1 more , Fortunato L

Int J Surg Oncol · 2012 · PMID 22655184 · Full text

Morphological criteria for the diagnosis of intraductal proliferative lesions of the breast have been an object of research and much controversy, and its terminology is rather confusing. Knowledge of the molecular aspect... Morphological criteria for the diagnosis of intraductal proliferative lesions of the breast have been an object of research and much controversy, and its terminology is rather confusing. Knowledge of the molecular aspects of this disease probably necessitates further research to clarify if these entities can be identified as breast cancer precursors or as a malignant preinvasive disease. These issues are of great interest not only for their biological implications, but also to the clinician who must understand the disease and direct therapies. Molecular studies have shown that epitheliosis (usual ductal hyperplasia) is not monoclonal, while malignant lesions (atypical ductal hyperplasia, flat epithelial atypia, low-grade and high-grade intraductal carcinoma) constantly show these characteristics. These malignant lesions, classified with a DIN grading system (ductal intraepithelial neoplasia), are not obligate precursors of invasive ductal carcinoma and do not represent different evolving grades in a linear model of cancerogenesis. Breast cancerogenesis probably has different pathways with different morphologic precursors.

The role of preoperative bilateral breast magnetic resonance imaging in patient selection for partial breast irradiation in ductal carcinoma in situ.

Kowalchik KV, Vallow LA, McDonough M … +7 more , Thomas CS, Heckman MG, Peterson JL, Adkisson CD, Serago C, Buskirk SJ, McLaughlin SA

Int J Surg Oncol · 2012 · PMID 22655183 · Full text

Purpose. Women with ductal carcinoma in situ (DCIS) are often candidates for breast-conserving therapy, and one option for radiation treatment is partial breast irradiation (PBI). This study evaluates the use of preopera... Purpose. Women with ductal carcinoma in situ (DCIS) are often candidates for breast-conserving therapy, and one option for radiation treatment is partial breast irradiation (PBI). This study evaluates the use of preoperative breast magnetic resonance imaging (MRI) for PBI selection in DCIS patients. Methods. Between 2002 and 2009, 136 women with newly diagnosed DCIS underwent a preoperative bilateral breast MRI at Mayo Clinic in Florida. One hundred seventeen women were deemed eligible for PBI by the NSABP B-39 (National Surgical Adjuvant Breast and Bowel Project, Protocol B-39) inclusion criteria using physical examination, mammogram, and/or ultrasound. MRIs were reviewed for their impact on patient eligibility, and findings were pathologically confirmed. Results. Of the 117 patients, 23 (20%) were found ineligible because of pathologically proven MRI findings. MRI detected additional ipsilateral breast cancer in 21 (18%) patients. Of these women, 15 (13%) had more extensive disease than originally noted before MRI, and 6 (5%) had multicentric disease in the ipsilateral breast. In addition, contralateral breast cancer was detected in 4 (4%). Conclusions. Preoperative breast MRI altered the PBI recommendations for 20% of women. Bilateral breast MRI should be an integral part of the preoperative evaluation of all patients with DCIS being considered for PBI.

Ductal carcinoma in situ: what can we learn from clinical trials?

Fortunato L, Poccia I, de Paula U … +1 more , Santini E

Int J Surg Oncol · 2012 · PMID 22649720 · Full text

Ductal Carcinoma in situ has been diagnosed more frequently in the last few years and now accounts for approximately one-fourth of all treated breast cancers. Traditionally, this disease has been treated with total maste... Ductal Carcinoma in situ has been diagnosed more frequently in the last few years and now accounts for approximately one-fourth of all treated breast cancers. Traditionally, this disease has been treated with total mastectomy, but conservative surgery has become increasingly used in the absence of unfavourable clinical conditions, if a negative excision margin can be achieved. It is controversial whether subgroups of patients with favourable in situ tumors could be managed by conservative surgery alone, without radiation. As the disease is diagnosed more frequently in younger patients, these issues are very relevant, and much research has focused on this topic in the last two decades. We reviewed randomized trials regarding adjuvant radiation after breast-conservative surgery and compared data with available retrospective studies.

Additional gastrectomy after endoscopic submucosal dissection for early gastric cancer patients with comorbidities.

Koide N, Takeuchi D, Suzuki A … +2 more , Ishizone S, Miyagawa S

Int J Surg Oncol · 2012 · PMID 22645672 · Full text

Purpose. We investigated the clinicopathologic features of early gastric cancer (EGC) patients who have undergone additional gastrectomy after endoscopic submucosal dissection (ESD) because of their comorbidities. Method... Purpose. We investigated the clinicopathologic features of early gastric cancer (EGC) patients who have undergone additional gastrectomy after endoscopic submucosal dissection (ESD) because of their comorbidities. Methods. Eighteen (7.1%) of 252 GC patients were gastrectomized after prior ESD. Reasons for further surgery, preoperative and postoperative problems, and the clinical outcome were determined. Results. The 18 patients had submucosal EGC and several co-morbidities. Other primary cancers were observed in 8 (44.4%). Histories of major abdominal operations were observed in 6 (33.3%). Fourteen patients (77.8%) hoped for endoscopic treatment. Due to additional gastrectomy, residual cancer was suspected in 10, and node metastasis was suspected in 11. A cancer remnant was histologically observed in one. Node metastasis was detected in 3 (16.7%). Small EGC was newly detected in 4. Consequently, additional gastrectomy was necessary for the one third. No patient showed GC recurrence. However, 9 (50%) had new diseases, and 4 (22.2%) died of other diseases. The overall survival after surgery in these patients with additional gastrectomy was poorer than those with routine gastrectomy for submucosal EGC (P = 0.0087). Conclusions. Additional gastrectomy was safely performed in EGC patients with co-morbidities. However, some issues, including presence of node metastasis and other death after surgery, remain.

Pancreatic fistula after pancreatectomy: definitions, risk factors, preventive measures, and management-review.

Machado NO

Int J Surg Oncol · 2012 · PMID 22611494 · Full text

Resection of pancreas, in particular pancreaticoduodenectomy, is a complex procedure, commonly performed in appropriately selected patients with benign and malignant disease of the pancreas and periampullary region. Desp... Resection of pancreas, in particular pancreaticoduodenectomy, is a complex procedure, commonly performed in appropriately selected patients with benign and malignant disease of the pancreas and periampullary region. Despite significant improvements in the safety and efficacy of pancreatic surgery, pancreaticoenteric anastomosis continues to be the "Achilles heel" of pancreaticoduodenectomy, due to its association with a measurable risk of leakage or failure of healing, leading to pancreatic fistula. The morbidity rate after pancreaticoduodenectomy remains high in the range of 30% to 65%, although the mortality has significantly dropped to below 5%. Most of these complications are related to pancreatic fistula, with serious complications of intra-abdominal abscess, postoperative bleeding, and multiorgan failure. Several pharmacological and technical interventions have been suggested to decrease the pancreatic fistula rate, but the results have been controversial. This paper considers definition and classification of pancreatic fistula, risk factors, and preventive approach and offers management strategy when they do occur.

Abdominoperineal resection for rectal cancer: is the pelvic drain externalization site an independent risk factor for perineal wound healing?

Pramateftakis MG, Raptis D, Kanellos D … +4 more , Christoforidis E, Tsoulfas G, Kanellos I, Lazaridis Ch

Int J Surg Oncol · 2012 · PMID 22611493 · Full text

Aim. The aim of this paper is to investigate if the insertion of the pelvic drainage tube via the perineal wound could be considered as an independent risk factor for perineal healing disorders, after abdominoperineal re... Aim. The aim of this paper is to investigate if the insertion of the pelvic drainage tube via the perineal wound could be considered as an independent risk factor for perineal healing disorders, after abdominoperineal resection for rectal malignancy. Patients and Methods. The last two decades, 75 patients underwent elective abdominoperineal resection for malignancy. In 42 patients (56%), the pelvic drain catheter was inserted through the perineal wound (PW group), while in the remaining 33 (44%) through a puncture skin wound of the perineum (SW group). Patients' data with respect to age (P = 0.136), stage (P > 0.05), sex (P = 0.188) and comorbidity (P = 0.128) were similar in both groups. 25 patients (PW versus SW: 8 versus 17, P = 0.0026) underwent neoadjuvant radio/chemotherapy. Results. The overall morbidity rate was 36%, but a significant increase was revealed in PW group (52.4% versus 9%, P = 0.0007). In 33.3% of the patients in the PW group, perineal healing was delayed, while in the SW group, no delay was noted. Perineal healing disorders were revealed as the main source of increased morbidity in this group. Conclusion. The insertion of the pelvic drain tube through the perineal wound should be considered as an independent risk factor predisposing to perineal healing disorders.

Cell polarity, epithelial-mesenchymal transition, and cell-fate decision gene expression in ductal carcinoma in situ.

Coradini D, Boracchi P, Ambrogi F … +2 more , Biganzoli E, Oriana S

Int J Surg Oncol · 2012 · PMID 22577534 · Full text

Loss of epithelial cell identity and acquisition of mesenchymal features are early events in the neoplastic transformation of mammary cells. We investigated the pattern of expression of a selected panel of genes associat... Loss of epithelial cell identity and acquisition of mesenchymal features are early events in the neoplastic transformation of mammary cells. We investigated the pattern of expression of a selected panel of genes associated with cell polarity and apical junction complex or involved in TGF-β-mediated epithelial-mesenchymal transition and cell-fate decision in a series of DCIS and corresponding patient-matched normal tissue. Additionally, we compared DCIS gene profile with that of atypical ductal hyperplasia (ADH) from the same patient. Statistical analysis identified a "core" of genes differentially expressed in both precursors with respect to the corresponding normal tissue mainly associated with a terminally differentiated luminal estrogen-dependent phenotype, in agreement with the model according to which ER-positive invasive breast cancer derives from ER-positive progenitor cells, and with an autocrine production of estrogens through androgens conversion. Although preliminary, present findings provide transcriptomic confirmation that, at least for the panel of genes considered in present study, ADH and DCIS are part of a tumorigenic multistep process and strongly arise the necessity for the regulation, maybe using aromatase inhibitors, of the intratumoral and/or circulating concentration of biologically active androgens in DCIS patients to timely hamper abnormal estrogens production and block estrogen-induced cell proliferation.
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