Pure Ductal Carcinoma In Situ of the Breast: Analysis of 270 Consecutive Patients Treated in a 9-Year Period.

INTRODUCTION: Ductal carcinoma in situ (DCIS) is an intraductal neoplastic proliferation of epithelial cells that are confined within the basement membrane of the breast ductal system. This retrospective observational analysis aims at reviewing the issues of this histological type of cancer. MATERIALS AND METHODS: Patients treated for DCIS between 1 January 2009 and 31 December 2018 were identified from a retrospective database. The patients were divided into two groups of 5 years each, the first group including patients treated from 2009 to 2013, and the second group including patients treated from 2014 to 2018. Once the database was completed, we performed a statistical analysis to see if there were significant differences among the 2 periods. Statistical analyses were performed using GraphPad Prism software for Windows, and the level of significance was set at p < 0.05. RESULTS: 3586 female patients were treated for breast cancer over the 9-year study period (1469 patients from 2009 to 2013 and 2117 from 2014 to 2018), of which 270 (7.53%) had pure DCIS in the final pathology. The median age of diagnosis was 59-year-old (range 36-86). In the first period, 81 (5.5%) women out of 1469 had DCIS in the final pathology, in the second, 189 (8.9%) out of 2117 had DCIS in the final pathology with a statistically significant increase (p = 0.0001). From 2009 to 2013, only 38 (46.9%) were in stage 0 (correct DCIS diagnosis) while in the second period, 125 (66.1%) were included in this stage. The number of patients included in clinical stage 0 increased significantly (p = 0.004). In the first period, 48 (59.3%) specimen margins were at a greater or equal distance than 2 mm (negative margins), between 2014 and 2018; 137 (72.5%) had negative margins. Between 2014 and 2018 the number of DCIS patients with positive margins decreased significantly (p = 0.02) compared to the first period examined. The mastectomies number increased significantly (p = 0.008) between the 2 periods, while the sentinel lymph node biopsy (SLNB) numbers had no differences (p = 0.29). For both periods analysed all the 253 patients who underwent the follow up are currently living and free of disease. We have conventionally excluded the 17 patients whose data were lost. Conclusion: The choice of the newest imaging techniques and the most suitable biopsy method allows a better pre-operative diagnosis of the DCIS. Surgical treatment must be targeted to the patient and a multidisciplinary approach discussed in the Breast Unit centres.

MRI to predict nipple-areola complex (NAC) involvement: An automatic method to compute the 3D distance between the NAC and tumor.

OBJECTIVES: To assess the role in predicting nipple-areola complex (NAC) involvement of a newly developed automatic method which computes the 3D tumor-NAC distance. PATIENTS AND METHODS: Ninety-nine patients scheduled to nipple sparing mastectomy (NSM) underwent magnetic resonance (MR) examination at 1.5 T, including sagittal T2w and dynamic contrast enhanced (DCE)-MR imaging. An automatic method was developed to segment the NAC and the tumor and to compute the 3D distance between them. The automatic measurement was compared with manual axial and sagittal 2D measurements. NAC involvement was defined by the presence of invasive ductal or lobular carcinoma and/or ductal carcinoma in situ or ductal intraepithelial neoplasia (DIN1c - DIN3). RESULTS: Tumor-NAC distance was computed on 95/99 patients (25 NAC+), as three tumors were not correctly segmented (sensitivity = 97%), and 1 NAC was not detected (sensitivity = 99%). The automatic 3D distance reached the highest area under the receiver operating characteristic (ROC) curve (0.830) with respect to the manual axial (0.676), sagittal (0.664), and minimum distances (0.664). At the best cut-off point of 21 mm, the 3D distance obtained sensitivity = 72%, specificity = 80%, positive predictive value = 56%, and negative predictive value = 89%. CONCLUSIONS: This method could provide a reproducible biomarker to preoperatively select breast cancer patients candidates to NSM, thus helping surgical planning and intraoperative management of patients.

Alterations in the brain adenosine metabolism cause behavioral and neurological impairment in ADA-deficient mice and patients.

Adenosine Deaminase (ADA) deficiency is an autosomal recessive variant of severe combined immunodeficiency (SCID) caused by systemic accumulation of ADA substrates. Neurological and behavioral abnormalities observed in ADA-SCID patients surviving after stem cell transplantation or gene therapy represent an unresolved enigma in the field. We found significant neurological and cognitive alterations in untreated ADA-SCID patients as well as in two groups of patients after short- and long-term enzyme replacement therapy with PEG-ADA. These included motor dysfunction, EEG alterations, sensorineural hypoacusia, white matter and ventricular alterations in MRI as well as a low mental development index or IQ. Ada-deficient mice were significantly less active and showed anxiety-like behavior. Molecular and metabolic analyses showed that this phenotype coincides with metabolic alterations and aberrant adenosine receptor signaling. PEG-ADA treatment corrected metabolic adenosine-based alterations, but not cellular and signaling defects, indicating an intrinsic nature of the neurological and behavioral phenotype in ADA deficiency.

2-Deoxy-d-Glucose Ameliorates PKD Progression.

Autosomal dominant polycystic kidney disease (ADPKD) is an important cause of ESRD for which there exists no approved therapy in the United States. Defective glucose metabolism has been identified as a feature of ADPKD, and inhibition of glycolysis using glucose analogs ameliorates aggressive PKD in preclinical models. Here, we investigated the effects of chronic treatment with low doses of the glucose analog 2-deoxy-d-glucose (2DG) on ADPKD progression in orthologous and slowly progressive murine models created by inducible inactivation of the Pkd1 gene postnatally. As previously reported, early inactivation (postnatal days 11 and 12) of Pkd1 resulted in PKD developing within weeks, whereas late inactivation (postnatal days 25-28) resulted in PKD developing in months. Irrespective of the timing of Pkd1 gene inactivation, cystic kidneys showed enhanced uptake of (13)C-glucose and conversion to (13)C-lactate. Administration of 2DG restored normal renal levels of the phosphorylated forms of AMP-activated protein kinase and its target acetyl-CoA carboxylase. Furthermore, 2DG greatly retarded disease progression in both model systems, reducing the increase in total kidney volume and cystic index and markedly reducing CD45-positive cell infiltration. Notably, chronic administration of low doses (100 mg/kg 5 days per week) of 2DG did not result in any obvious sign of toxicity as assessed by analysis of brain and heart histology as well as behavioral tests. Our data provide proof of principle support for the use of 2DG as a therapeutic strategy in ADPKD.

Laparoscopic repair of ventral hernia in a laparoscopic experienced surgical center: low recurrence rate, morbidity, and chronic pain are achievable.

PURPOSE: Recurrence rate and the perioperative outcome evaluation through laparoscopic approach for ventral (primary and incisional) hernia repair. MATERIALS AND METHODS: A retrospective evaluation of a series of patients treated through a minimally invasive approach for ventral hernia was performed. A standardized surgical technique was adopted. All the patients were evaluated through a clinical follow-up. RESULTS: From July 2004 to June 2011, 150 videolaparoscopic ventral hernia repairs were performed. The median follow-up was 40 months. One hernia recurrence (0.7%) was detected after 55 months. The intraoperative and postoperative complication rate was 2.6% (1 conversion to open surgery) and 5.3%, respectively. Chronic pain nonresponsive to drug was registered in 2 patients (1.3%). CONCLUSIONS: The videolaparoscopic approach to ventral hernia repair is a safe technique that can guarantee a low recurrence rate; moreover, if it is performed in an experienced laparoscopic surgical center, it can be a valid alternative to the traditional open approach.

Glove technique in single-port access laparoscopic surgery: results of an initial experience.

Introduction. Single-incision laparoscopic surgery (SILS) is a virtually "scarless" technique. A retrospective analysis is performed to evaluate an initial experience of this surgical approach. Materials and Methods. From January 2010 to October 2011, SILS was considered as a minimally invasive approach to abdominal disease. The access was made by a standard wound protector and a size 6 glove. A series of little accesses were made on the tips of the glove-fingers to induce pneumoperitoneum and to create a working channel for the laparoscopic instruments. An analysis of costs of this technique was made too. Results. SILS was successfully completed with low cost in 34 patients: 20 appendectomy, 12 cholecystectomy, and 2 right colectomy were performed with a median operative time of 35, 45, and 67.5 minutes, respectively. In no patient any conversion to standard laparoscopy or to open surgery was needed. The postoperative course was uneventful in all patients. In right hemicolectomy, the oncological parameters were respected. Conclusions. In this paper the glove-port technique showed multiple advantages. The SILS is a feasible approach for some pathologies in selected patients. The glove-port is a simple, low-cost, reproducible, and sure method to perform SILS in a high-experienced laparoscopic surgical centre.

The role of micrometastatic disease in sentinel lymph node in breast cancer.

Sentinel lymph node (SLN) biopsy is the standard procedure for axillary node staging in breast cancer. Improvements in histopathological analysis and immunohistochemistry have recently increased the rate of detection of lymph nodal micrometastases. The clinical implications and prognostic significance of micrometastases in SLN still remain a controversial issue. Literature review was analyzed by searches of Medline and PubMed data bases. Whereas most studies carried on small groups of patients did not show differences in survival, recently some studies with longer follow-up and with larger populations demonstrated that prognosis of patients with micrometastases is worse compared to that of patients with SLN free of disease. To date, completion axillary dissection remains the standard option when a macro or micrometastasis (0.2-2 mm) in the SLN is found. However, in absence of level-1 evidence guidelines, each case requires discussion in the context of a multi-disciplinary team.

Identifying factors contributing to reduced breast tumor size: a longitudinal study.

AIM: This study examines the trends and outcomes of breast cancer patients who have undergone surgical procedures at the Department of Surgical Sciences, University of Insubria, Varese, Italy. It also identifies the factors that contributed to the reduction of the breast tumor size over a 13-year period at a tertiary referral center. METHODS: All breast cancer operations performed at the Department of Surgical Sciences, University of Insubria, Varese, Italy, from January 1992 to June 2005 were examined and data from their surgical pathology reports were also analyzed, using a prospective database. A longitudinal study was performed to compare and analyze the pathological data during three consecutive time periods. The periods were from 1992 to 1996, 1997 to 1999, and 2000 to 2005. Surgical and pathological outcomes included age of the patient at the time of the diagnosis, partial breast resections, mastectomies, axillary lymphadenectomies, tumor size, histological type and stage, and lymph node status. RESULTS: The study group was comprised of 3050 patients who underwent breast resection between 1992 and 2005. Quadrantectomy was the preferred surgical approach in 1759 patients (58%). Throughout the longitudinal study, the tumors measuring less than 1cm increased from 13.4% to 15.4%; the number of tumors diagnosed at stage I increased from 44.1% to 56.8%; the most frequent histological type was ductal carcinoma; the number of ductal carcinomas in situ (DCIS) increased from 4% to 6%; and the incidence of lymphadenectomies decreased from 71.6% to 52.5%. Perioperative factors that correlated with the decreased size of the tumor over time were: screening, improvement of diagnostic and therapeutic techniques, and the increased operative use of sentinel lymph node biopsy (SLNB). CONCLUSIONS: There has been an evolving refinement in surgical technique and perioperative management of breast cancer patients undergoing surgical resection at the Department of Surgical Sciences, University of Insubria, Varese, Italy, during the past decades. The present longitudinal study on 3050 surgical breast cancer patients confirmed the progressive reduction of tumor size at the time of the diagnosis. Perioperative factors that correlated with the decreased tumor size over time were mammography screening, improvement of diagnostic and therapeutic techniques, and the use of SLNB. Furthermore, the study showed that the progressive reduced number of useless axillary lymphadenectomies was mainly due to the increased intraoperative use of axillary SLNB.

Medullary thyroid carcinoma: surgical treatment advances.

Since medullary thyroid cancer (MTC) was first recognized as a distinct tumor in 1959, it became clear that MTC is more difficult to cure than papillary thyroid cancer and has higher rates of recurrence and mortality. MTC represents 5-8% of thyroid cancers. It derives from parafollicular cells of the ultimobranchial body derived from the neural crest. MTC secretes calcitonin and other hormonal peptides and is considered part of the amine precursor uptake and decarboxilation system. MTC may occur either as a hereditary or nonhereditary entity. Hereditary MTC can occur either alone as the familial MTC or as the thyroid manifestation of multiple endocrine neoplasia (MEN) type 2 syndromes (MEN 2A MEN 2B). Activating point mutations of the RET proto-oncogene have demonstrated to be causative of the familial form of medullary thyroid cancer, both isolated familial MTC and associated with MEN 2A and 2B. In the last 10 years, major improvements and new technologies have been proposed and applied in thyroid surgery; among these are molecular diagnosis with genetic screening and mini-invasive video-assisted thyroidectomy. The history of thyroid surgery starts with Billroth, Kocher and Halsted, who developed the technique for thyroidectomy between 1873 and 1910. Prophylactic surgery for patients carrying a positive RET proto-oncogene has proven to be highly effective in curing those likely to experience the development of MTC. Video-assisted procedures with central compartment dissection have proved feasible for patients carrying a positive RET proto-oncogene. This paper reviews relevant medical literature published in the English language on surgery of MTC in well-controlled trials. We discuss the particular ethical and legal issues that thyroid prophylactic surgery raises. Searches were last updated in February 2007.

Sentinel lymph node biopsy as the new standard of care in the surgical treatment for breast cancer.

During the recent years, based on the results of validation studies, the sentinel lymph node biopsy has replaced routine axillary dissection as the new standard of care in early breast cancer. The technique represents a minimally invasive, highly accurate method for axillary staging, which could spare approximately 65-70% of patients unnecessary axillary dissection and its related morbidity. Several technical and clinical controversies have been raised during the development of this new technique; the authors review the most important issues, some questions have already been answered and others are still under debate. As far as the technical aspects are concerned, mapping techniques, appropriate surgical training, options for pathological examination of sentinel lymph nodes and the issue of nonaxillary sentinel lymph nodes are discussed. An update on clinical controversies demonstrates that factors such as large tumor size, palpable axillary nodes, multifocality and multicentricity, previous breast and axillary surgery, and pregnancy are no longer regarded as absolute contraindications for sentinel lymph node biopsy. Feasibility, accuracy and timing of sentinel lymph node biopsy in patients undergoing neoadjuvant chemotherapy remain unsolved issues, as well as the indication of the technique for some subgroups of in situ lesions. Finally, one of the most attractive open forums for debate will be discussed: whether or not completion of axillary dissection in the case of positive SLN is always required.

Mechanical bowel preparation for colorectal surgery.

BACKGROUND: Nosocomial infections are the most frequent complications of surgical patients. Most surgical site infections (SSI) are acquired intraoperatively and arise from the flora of the patient's skin, gastrointestinal tract, or mucous membranes. Although preoperative mechanical cleansing of the bowel is considered by many surgeons a cornerstone of modern elective colorectal surgery and, in association with antibiotic prophylaxis, a fundamental component of an intestinal antisepsis program, many surgeons do not perform preoperative mechanical preparation routinely. METHODS: Review of the pertinent literature. RESULTS: Some recent randomized trials and a Cochrane review found no proof that mechanical bowel preparation reduces the risk of complications after elective colorectal surgery. Indeed, there is some evidence that this intervention is associated with a higher rate of anastomotic leakage and wound complications. CONCLUSIONS: The dogma that mechanical bowel preparation is necessary before elective colorectal surgery may need to be reconsidered. On the other hand, such preparation decreases operating time by improving bowel handling during construction of the anastomosis. Moreover, it is helpful when intestinal palpation will be necessary for identification of a lesion.