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Background: The continuous increase in the rate of nipple sparing mastectomy (NSM), the development of several reconstructive techniques and the following introduction of acellular derma matrix (ADM) has revolutionized implant-based breast reconstruction. This study aimed to investigate postoperative complications, health-related quality of life (HRQoL) and patients' satisfaction in patients undergoing NSM and breast reconstruction with or without ADM., Methods: Enrolled patients were divided into three groups: immediate breast reconstruction (IBR) with definitive implant and ADM (Group A), IBR only with definitive prosthesis (Group B), and two-stage breast reconstruction (Group C). The postoperative complications, BREAST-Q outcomes and reoperations were compared., Results: A total of 105 BC patients were enrolled and a total of 139 post-mastectomy breast reconstructions were performed. Seroma was the most prevalent complication observed: 8.3% in Group A, 2.9% in Group B and 5.7% in Group C. Postoperative infection occurred in two patients of Group A (5.6%), one patient of Group B (2.9%) and one of Group C (2.9%). Group A reported larger drain volume (1,125±243.5 cc), longer drain period (13.2±2.8 days), and the lowest incidence of capsular contracture (5.6%). The BREAST-Q patient-reported outcome measures document that all patients aged ≥50 years presented a higher score in "Satisfaction with breast" (P<0.001) and "Satisfaction with outcome" domains (P<0.05). Performing a bilateral breast reconstruction was associated to higher scores in "Physical wellbeing chest domain" (P<0.05). In addition, patients in Group A and Group B reported higher score in "Satisfaction with the breast" domain (P<0.001) but only in Group B we reported a higher score in "Satisfaction with outcome" (P<0.001)., Conclusions: Subpectoral IBR results in manageable complications and greater personal satisfaction. The ADM could improve breast reconstruction reducing the rate of capsular contracture. The prepectoral placement of ADM could minimize complications and optimize aesthetic results., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-58/coif). The authors have no conflicts of interest to declare., (2024 Gland Surgery. All rights reserved.)

Background: In the last decade, two research groups, the French group by Clough et al. (Br J Surg. 97:1659-65, 2010) and the Chinese one by Li et al. (ISRN Oncol 2013:279013, 2013), proposed two types of classification of axillary lymph nodes in breast cancer, identifying novel anatomic landmarks for dividing the axillary space in lymph node dissection., Main Body: Knowledge of the exact location of the sentinel node helps to focus the surgical dissection and to reduce the morbidity of sentinel lymph node biopsy procedures, in particular the risk of arm lymphedema, without compromising sensitivity., Conclusion: In this article, we aimed at focusing on the clinical impact that the most recent classifications of axillary lymph nodes have obtained in literature, highlighting the importance of defining new demarcations to preserve the axillary lymph nodes as much as possible in breast surgery.

Background: Breast cancer (BC) is the most common cancer among women in developed countries. Several types of surgical interventions are commonly used in BC, such as mastectomy and quadrantectomy, followed by radiation or not. Today, BC rehabilitation can help survivors obtain and maintain the highest physical, social, psychological, and vocational functioning possible, within the limits that are created by cancer and its treatments., Objective: To verify, before and after a specific rehabilitation protocol treatment, the recovery of the fluidity of the reaching movement., Methods: Patients after BC surgery were enrolled and assigned by cluster randomization into 2 groups through a block randomization list: mastectomy (Mas) and quadrantectomy (Quad). Evaluation scales (DASH and VAS) were administered, and biomechanical evaluations were performed for each group before treatment (T0 = baseline), at the end of the rehabilitative treatment (T1 = 12 sessions, 2/week), and after 3 months of follow-up (T2)., Results: Fifty-nine (Mas group = 29; Quad group = 30) after BC surgery were enrolled. VAS scores improved along the evaluation times at T0-T1 and T0-T2 (p < 0.001), without a statistically significant difference between groups. With regard to the normalized jerk, there was no significant interaction between time group (F = 2.029; p = 0.136). There was a significant decrease between T0-T1 and T1-T2 (F = 60.189; p < 0.001). Velocity improved significantly between T0-T1 and T1-T2 (F = 10.322; p < 0.001). There was a significant interaction for the elbow angle at the end of movement between time and group at T2 (F = 5.022; p = 0.029)., Conclusion: The integrated, low-intensity, rehabilitative intervention is effective, even if it is not performed in the first period after BC surgery, without any difference between mastectomy and quadrantectomy.

Background: Barriers to palliative care still exist in long-term care settings for older people, which can mean that people with advanced dementia may not receive of adequate palliative care in the last days of their life; instead, they may be exposed to aggressive and/or inappropriate treatments. The aim of this multicentre study was to assess the clinical interventions and care at end of life in a cohort of nursing home (NH) residents with advanced dementia in a large Italian region., Methods: This retrospective study included a convenience sample of 29 NHs in the Lombardy Region. Data were collected from the clinical records of 482 residents with advanced dementia, who had resided in the NH for at least 6 months before death, mainly focusing on the 7 days before death., Results: Most residents (97.1%) died in the NH. In the 7 days before death, 20% were fed and hydrated by mouth, and 13.4% were tube fed. A median of five, often inappropriate, drugs were prescribed. Fifty-seven percent of residents had an acknowledgement of worsening condition recorded in their clinical records, a median of 4 days before death., Conclusions: Full implementation of palliative care was not achieved in our study, possibly due to insufficient acknowledgement of the appropriateness of some drugs and interventions, and health professionals' lack of implementation of palliative interventions. Future studies should focus on how to improve care for NH residents.

Introduction : Cachexia is frequent in chronic diseases and especially during cancer development. Multiple definitions of cachexia have been proposed; it may be considered a multifactorial complex syndrome that presents with progressive unintentional weight loss and wasting of muscle mass and adipose tissue. Area covered : This article covers phase-I and phase-II clinical trials of investigational drugs for cancer cachexia. We performed a search on PubMed with keywords as cancer cachexia, phase-I/phase-II trial, drug, identifying articles relevant to this review. Studies were conducted using compounds, including anabolic agents such as ghrelin analogs, selective androgen receptor modulators, as well as anti-inflammatory drugs such as thalidomide, OHR, anti-interleukin antibody, cannabinoids, and omega-3 supplements. We also describe the mechanisms of action of these molecules and their phase-I and phase-II study design. The major outcomes were appetite stimulation, weight gain, improvement of muscle mass and function, modulation of inflammation, and quality of life. Expert opinion : The molecules discussed act on molecular pathways involved in cancer cachexia; they modulate appetite, anabolic effects, inflammation and direct interaction with muscle. Considering the multifactorial aspects of the cachexia syndrome, the combination of these drugs with metabolic and nutritional interventions may represent the most promising therapeutic approach to cancer cachexia.

Multiple primary malignant neoplasms are multiple tumors with different pathogenetic origin. They may be synchronous or metachronous. The management of these conditions represents an interesting clinical scenario. A crucial aspect is the decision regarding which tumor to treat initially, and how to schedule further treatments according to individual tumor risk. This process involves a multidisciplinary physician team to ensure favorable outcomes. We describe a case report of a female patient affected by primary synchronous tumors of the breast and pectoral skin, which raised a series of diagnostic, etiological and therapeutic issues persuading us to carry out a critical review of the literature., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Rationale: Low physical activity is frequent in end stage renal disease. We evaluated the longitudinal change in physical activity and its barriers in hemodialysis (HD) patients and the association between the patterns of physical activity change, body composition, and beta-aminoisobutyric acid (BAIBA), as circulating myokine. Methods: This is an observational study, where HD patients were considered in a 24-month follow-up. We assessed overtime the change of physical inactivity and its barriers by validated questionnaires, body composition by bioimpedance analysis, muscle strength by hand-dynamometer, and plasma BAIBA levels by liquid chromatography spectrometry. Parametric and non-parametric analyses were performed, as appropriate. Results: Out of the 49 patients studied at baseline, 39 completed the first-year follow-up, and 29 completed the second year. At month 12, active patients had higher intracellular water (ICW) ( P = 0.001) and cellular mass ( P < 0.001), as well as at month 24 ( P = 0.012, P = 0.002; respectively) with respect to inactive. A significant reduction in ICW was shown at month 12 ( P = 0.011) and month 24 ( P = 0.014) in all patients. The barrier "reduced walking ability" was more frequent in inactive patients with respect to active at month 12 ( P = 0.003) and at month 24 ( P = 0.05). At month 24, plasma BAIBA levels were higher among active patients with respect to inactive ( P = 0.043) and a correlation was seen between muscle strength and ICW ( r = 0.51, P = 0.005); normalizing BAIBA per body mass index, we found it lower with respect to baseline ( P = 0.004), as well as after correcting per ICW ( P = 0.001), as marker of muscle mass. Conclusion: A high prevalence of physical inactivity persisted during a 24-month follow-up in this cohort. We found an association between physical activity and a decline in marker of muscularity and reduced plasma BAIBA levels.

Rationale and Objectives: The aim of this study was to retrospectly investigate the association between different breast cancer (BC) immunohistochemical subtypes and morphological and semiquantitative kinetic analysis on breast magnetic resonance imaging (MRI) performed before surgery treatment. Specifically we aimed to assess MRI features of triple-negative breast cancer (TNBC) compared to the other BC subtypes (nTNBC)., Materials and Methods: Patients undergone to breast MRI and then diagnosed with BC by core-needle biopsy were included. The MRI morphological and kinetic features were studied. Parametric and non-parametric tests were used, as appropriate., Results: Seventy-five BC patients were considered, 30 patients included in TNBC Group and 45 patients included in nTNBC Group. We found in TNBC Group a greater mean lesion size (P <0.001), a rim enhancement imaging (P=0.003), and a higher intratumoral signal intensity on T2-weighted images (P=0.03) with respect to nTNBC Group. We noticed that TNBC patients presented a lower grade of BPE when compared to the nTBC Group (P< 0.02). TNBC Group showed lower EPeak values (P=0.003) and higher SER values (P=0.02) with respect to the nTNBC Group. In addition, stratifying kinetics parameters according to the tumor grade, the TNBC Group presented higher tumor grade (G3) (P< 0.005) and this subgroup had higher SER values when compared to TNBCs showing a lower tumor grade (G1 and G2) (P=0.03)., Conclusion: After validation by large-scale studies, the morphological and semiquantitative kinetic analysis on dynamic contrast enhanced MRI may help in the pretreatment risk stratification of patients with TNBC and in evidence-based clinical decision support., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

Introduction: The omega-3 polyunsaturated fatty acids, as docosahexaenoic acid (DHA), are considered mediators regulating the resolution of inflammation during cancer and may be associated with better outcomes. Epoxydocosapentaenoic acids (EDPs), metabolites of the DHA, are hypothesized to be responsible for some beneficial effects. In the present study, we aimed to assess the circulating 19,20-EDP levels in breast cancer (BC) patients and in healthy controls before and after DHA oral supplementation and the potential differences in the DHA conversion in 19,20-EDPs between patients with different BC presentations., Methods: BC patients and healthy controls were supplemented with DHA (algal oil) for 10 days (2 g/day). Blood samples were collected at baseline (T0) and after supplementation (T1) to assess EDP (19,20-EDP) serum levels by liquid chromatography spectrometry., Results: 33 BC patients and 10 controls were studied. EDP values at T0 were not different between patients and controls. At T1, we found an increase in 19,20-EDP levels in BC patients ( P < 0.00001) and in controls ( P < 0.001), whereas no differences in 19,20-EDPs were present between the two groups; when considering the type of BC presentation, patients with BRCA1/2 mutation showed lower 19,20-EDPs levels with respect to BC patients without the mutation ( P = 0.03). According to immunohistochemical subtype, luminal A-like BC patients showed at T1 higher 19,20-EDP levels compared to nonluminal A ( P = 0.02)., Conclusions: DHA oral supplementation was associated with increased 19,20-EDP serum levels in BC patients, independent of the type of BC presentation, and in controls. Patients carrier of BRCA1/2 mutation seem to possess lower ability of DHA epoxidation, whereas luminal A-like BC patients showed higher EDP conversion. This behavior should be tested in a larger population.

We evaluated the impact of breast cancer subtypes on pathologic complete response (pCR) in 181 patients with positive nodes undergoing neoadjuvant chemotherapy (NAC). After NAC, patients underwent surgery, with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND). In 28.2% of cases a pCR was achieved, with the highest rate in Her2+ and triple negative tumors. Overall, nodal pCR was more frequent than breast pCR (P = 0.003) with higher percentages in Her2+ and LLB-Her2+ (P < 0.05). In the Her2+ group, nodal pCR was observed only with breast pCR. Thus, in Her2+ tumors, breast pCR predicts node pCR, supporting the use of SLNB in this subgroup to stage the axilla avoiding ALND., (© 2019 Wiley Periodicals, Inc.)

Context: End-of-life care in nursing homes (NHs) needs improvement. We carried out a study in 29 NHs in the Lombardy Region (Italy)., Objectives: The objective of this study was to compare end-of-life care in NH residents with advanced dementia before and after an educational intervention aimed to improving palliative care., Methods: The intervention consisted of a seven-hour lecture, followed by two 3-hour meetings consisting of case discussions. The intervention was held in each NH and well attended by NH staff. This multicenter, comparative, observational study included up to 20 residents with advanced dementia from each NH: the last 10 who died before the intervention (preintervention group, 245 residents) and the first 10 who died at least three months after the intervention (postintervention group, 237 residents). Data for these residents were collected from records for 60 days and seven days before death., Results: The use of "comfort hydration" (<1000 mL/day subcutaneously) tended to increase from 16.9% to 26.8% in the postintervention group. The number of residents receiving a palliative approach for nutrition and hydration increased, though not significantly, from 24% preintervention to 31.5% postintervention. On the other hand, the proportion of tube-fed residents and residents receiving intravenous hydration decreased from 15.5% to 10.5%, and from 52% to 42%, respectively. Cardiopulmonary resuscitations decreased also from 52/245 (21%) to 18/237 (7.6%) cases (P = 0.002)., Conclusion: The short educational intervention modified some practices relevant to the quality of end-of-life care of advanced dementia patients in NHs, possibly raising and reinforcing beliefs and attitudes already largely present., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: It is generally accepted that the efficacy with an intragastric balloon decreases after the first 4 months of treatment. Aim of this study is to evaluate if the association of a very low-calorie ketogenic diet (VLCKD) can improve the results in terms of weight loss parameters and co-morbidities, as compared to usually prescribed low-calorie diet (LCD)., Methods: For the present study (January 2016-June 2017), 80 patients (20 M/60 F, mean age 37.8 ± 6.1 years; excess weight 56 ± 10 kg; mean BMI 37.2 ± 3.8 kg/m 2 ) underwent Orbera positioning. After 4 months, they were randomized into two groups according to the type of treatment: group A (Bioenterics intragastric balloon - Orbera + VLCKD) (n = 40), and group B (Orbera + LCD) (n = 40)., Results: All patients completed the study with good adherence to diet therapy treatment allocation. After the 6-month treatment period, at time of Orbera removal, mean weight loss was 19 kg and 12 kg in groups A and B respectively (p < 0.05). Mean BMI was 28.9 ± 2.8 and 31.6 ± 3.1 kg/m 2 (p < 0.05), and %EWL was 33.1 ± 3.3 and 21.1 ± 2.9 (p < 0.05) in groups A and B respectively. During the last 2 months in group A, the mean weight loss was 8 kg, while in Group B, the main weight loss was 3 kg (p < 0.001). The VLCKD treatment induced a more significant reduction of major comorbidities related to metabolic syndrome., Conclusions: This study clearly indicates the efficacy of the prescription of very low-calorie ketogenic diet improving the efficacy of intragastric balloon positioning.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1 , PD-L2 , CD80 , and CD86 was evaluated at the mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the downregulation of CD80 was observed above all in ATC. In addition, the increased expression of CD80 associated with longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAF V600E mutation in PTC. The increased PD-L2 expression correlated with BRAF V600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 downregulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC.

Background: Comfort may be an appropriate goal in advanced dementia. Longitudinal studies on physician decision-making and discomfort assessed by direct observation are rare, and intravenous rehydration therapy is controversial., Methods: To assess treatment decisions and discomfort in patients with advanced dementia and pneumonia and to compare by intravenous rehydration therapy, we used data from the observational multicenter Italian End of Life Observatory-Prospective Study On DEmentia patients Care. We analyzed 109 episodes of pneumonia, which involved decisions in 77 nursing home patients with Functional Assessment Staging Tool stage 7. We assessed decisions, decision-making, and treatments every fortnight. Trained observers assessed discomfort with the Discomfort Scale-Dementia Alzheimer Type (DS-DAT)., Results: Most decisions referred to treatment with antibiotics (90%; 98 of 109) and intravenous rehydration therapy (53%; 58 of 109), but hospitalization was rare (1%). Selecting decisions with antibiotics, with rehydration therapy, the prognosis was more frequently <15 days (34% vs 5% without rehydration therapy; P = .001), and a goal to reduce symptoms/suffering was more common (96% vs 74%; P = .005) while there was no difference in striving for life prolongation (a minority). With rehydration therapy, the decision was more often discussed with family rather than communicated only. Mean DS-DAT scores over time proximate to the first decision ranged between 9.2 and 10.5., Conclusions: Italian nursing home patients with advanced dementia and pneumonia frequently received invasive rehydration therapy in addition to antibiotics, however, mostly with a palliative intent. Discomfort was high overall and symptom relief may be improved. Relations between invasive rehydration therapy and discomfort need further study.

Breast lipofilling uses autologous fat grafting to correct breast defects after radical or conservative surgery. After early concerns regarding its application in reconstruction after breast cancer (BC), in 2009 the American Society of Plastic Surgeons formed a task force to assess the indications, safety and efficacy of autologous fat grafting. We report the case of a woman who came to our attention for a painful swelling of the left breast. She had undergone breast-conserving therapy for BC, followed by lipofilling. The breast ultrasound (US) examination showed diffuse structural alteration and multiple hypoechoic areas with acoustic shadowing, mainly localized in the subcutaneous tissue. After pharmacological treatment and short-term follow-up US examination, considering the persistence of the clinical symptoms and structural alterations, we performed contrast-enhanced magnetic resonance imaging, that showed multiple enhancing areas in the left breast. Suspecting local tumor recurrence, we carried out US-guided breast core-biopsy, whose histological examination documented liponecrosis. This observation raised a series of diagnostic and therapeutic issues highlighting the diagnostic pitfalls that the radiologist may encounter during the evaluation of patients who have undergone BC surgery and breast reconstruction through lipofilling., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Higher survival rates for breast cancer patients have led to concerns in dealing with short- and long-term side effects. The most common complications are impairment of shoulder functions, pain, lymphedema, and dysesthesia of the injured arm; psychological consequences concern: emotional distress, anxiety, and depression, thereby, deeply impacting/affecting daily living activity, and health-related quality of life., Objective: To perform a systematic review for assessing the efficacy or effectiveness of interventions aiming at improving health-related quality of life, return to daily activity, and correct lifestyles among breast cancer patients., Methods: A literature search was conducted in December 2016 using the databases PubMed and Scopus. Search terms included: (counseling) AND (breast cancer) AND (quality of life). Articles on counseling interventions to improve quality of life, physical and psychological outcomes were included., Results: Thirty-five articles met the inclusion criteria. The interventions were grouped in five main areas: concerning lifestyle counseling interventions, related to combined interventions (physical activity and nutritional counseling), physical therapy, peer counseling, multidisciplinary approach, included psychological, psycho-educational interventions, and cognitive-behavior therapy (CBT). Exercise counseling as well as physical therapy are effective to improve shoulder mobility, healing wounds, and limb strength. Psychological therapies such as psychoeducation and CBT may help to realize a social and psychological rehabilitation., Conclusion: A multidisciplinary approach can help in sustaining and restoring impaired physical, psychosocial, and occupational outcomes of breast cancer patients.

According to the American Association of Cancer Research (AACR), a Cancer Stem Cell is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that constitutes the tumor [1]. Cancer Stem Cells (CSCs) are involved in the metastatic process, in the resistance to therapeutic treatments of many types of human cancers and consequently in the onset of recurrences. Numerous translational studies have been conducted to understand CSC characteristics and evaluate association between CSC-related biomarkers and clinical outcomes. The CSC theory can explain also a tumor relapse after that a tumor has been completely surgically removed (R0 macroscopical zero residual resection) or after an apparently complete response to chemotherapy. CSCs, in fact, showed a marked ability to reduce intracellular accumulation of chemotherapic agents by active drug extrusion, increased chemoresistance and survival, as well as elevated membrane transporter activity. In addition, it is possible that these cancer stem cells may nest in the "secured" (niche) sites of our body, where they may remain undisturbed for a long time, even years, until a stimulus arrives to awaken them, causing the disease to resume. CSCs, in fact, are able to use a variety of cellular pathways to survive to anticancer treatments. More recently CSCs have been described in several solid tumors, expressing specific biomarkers. Another field of research should be focused on the realization of diagnostic instruments to follow up patients after R0 surgical resection or after a complete response for an early detection and management of relapse and metastasis.

Breast-oncoplastic surgery, allowing local tumor control and a better cosmetic outcome, is oncologically safe when applied to early-stage breast cancer. Breast cancer recurrence following conservative therapy may occur during the first 5 years after treatment, with a peak incidence after 2 years. Therefore, during the follow-up period, patients undergo a series of ultrasound (US) and mammographic examinations. However, after surgery and radiation therapy, several modifications occur in the treated breast, causing difficulties in image interpretation, especially when local recurrence is suspected. Although not included in routine follow-up, magnetic resonance imaging (MRI) is often used in clinical practice, being considered more sensitive than the conventional imaging examinations in discriminating between postsurgical tissue modifications and tumor recurrence. In this review article, we analyze expected and pathologic breast MRI findings after conservative oncoplastic surgery compared to US and mammographic findings in order to distinguish local recurrence and avoid potential pitfalls in image interpretation.

Cumulative long-term exposure to solar ultraviolet radiation promotes premature skin aging characterized by wrinkle formation and reduced skin elasticity. In this study, we assessed whether microfat transfer could improve dermal and subcutaneous tissue thickness loss associated with photoaging. Twenty-one patients affected by facial photoaging (photodamage grade II-IV; age range 35-62 years; 19 females, 2 males; all of Caucasian origin) were treated using minimally invasive autologous dermal white fat transfer harvested with a recently designed microcannula. The results were determined by clinical assessment and patient self-evaluation and quantified by the Antera 3D ® dermal digital device for noninvasive, objective, reliable, and accurate assessment of facial skin texture, color, and wrinkle characteristics. Compared with the pretreatment condition, the increment in soft tissue volume and improvement in skin quality and texture were assessed by a dermatologist after treatment. In addition, instrumental evaluation by digital skin profilometry of the treated areas revealed a 41% reduction in average wrinkle depth (7.29 ± 1.04 × 10 -2  mm pretreatment vs. 4.31 ± 1.16 × 10 -2  mm at 90 days posttreatment; p < 0.001), improved skin texture, more homogeneous and uniform skin color, and declined facial hemoglobin and melanin concentrations. The majority of patients (above 90%) reported improvements in self-perception. No significant complications were reported throughout the study. In conclusion, by using digital profilometry analysis as an objective and innovative tool to determine the outcome of treatment, we demonstrated that autologous microfat transfer is a safe and well-tolerated procedure with measurable beneficial effects on facial skin aging., (Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Rationale: Docosahexaenoic acid (DHA) in cell membrane may influence breast cancer (BC) patients' prognosis, affecting tumor cells sensitivity to chemo- and radio-therapy and likely modulating inflammation. The possibility of identifying BC patients presenting with low DHA levels and/or low ability of DHA incorporation into cell membrane might help to treat this condition. Methods: We enrolled BC patients and healthy controls, recording their seafood dietary intake. DHA in form of algal oil was administered for 10 consecutive days (2 g/day). Blood samples were collected at baseline (T0) and after 10 days of supplementation (T1) to assess DHA, omega-3 index, as the sum of DHA + eicosapentaenoic acid (EPA), in red blood cells (RBC) membranes and plasma tumor necrosis factor-alpha and interleukin-6 levels. Pre- and post-treatment fatty acid profiles were obtained by gas-chromatography. Parametric and non-parametric tests were performed, as appropriate, and P -value < 0.05 was considered statistically significant. Results: Forty-three women were studied, divided into 4 groups: 11 patients with BRCA1/2 gene mutation (M group), 12 patients with familiar positive history for BC (F group), 10 patients with sporadic BC (S group), and 10 healthy controls (C group). DHA and omega-3 index increased from T0 to T1 in the 3 groups of BC patients and in controls ( P < 0.001). No difference was found in DHA incorporation between each group of BC patients and between patients and controls, except for M group, which incorporated higher DHA levels with respect to controls (β = 0.42; P = 0.03). No association was documented between cytokines levels and DHA and omega-3 index at baseline and after DHA supplementation. Independent of the presence of BC, women considered as "good seafood consumers" showed at baseline DHA and omega-3 index higher with respect to "low seafood consumers" ( P = 0.04; P = 0.007, respectively). After supplementation, the increase in DHA levels was greater in "low seafood consumers" with respect to "good seafood consumers" ( P < 0.0001). Conclusion: DHA supplementation was associated with increased DHA levels and omega-3 index in RBC membranes of BC cancer patients, independent of the type of BC presentation, and in controls. BRCA1/2 mutation, as well as low seafood consuming habits in both BC patients and healthy controls, seem to be associated with greater ability of DHA incorporation. Larger samples of BC patients are necessary to confirm our observation.

Establishment and maintenance of the apical-basal cell polarity, required for proper replication, migration, specialized functions and tissue morphogenesis, relies on three evolutionary conserved complexes: PAR, CRUMBS and SCRIBBLE. Loss of cell polarity/cohesiveness (LOP/C) is implicated in cancer progression, and members of the polarity complex have been described as either oncogenes or oncosuppressors. However, no information on their role in thyroid cancer (TC) progression is available. In the present study, we evaluated the gene expression of the PAR complex members aPKCι, PARD3α/β and PARD6α/β/γ in 95 papillary TC (PTC), compared to their normal matched tissues and in 12 anaplastic TC (ATC). The mRNA and protein levels of investigated genes were altered in the majority of PTC and ATC tissues. In PTC, univariate analysis showed that reduced expression of aPKCι, PARD3β and PARD6γ mRNAs is associated with increased tumor size, and the reduced expression of PARD3β mRNA is associated also with recurrences. Multivariate analysis demonstrated that the presence of lymph node metastasis at diagnosis and the reduced expression of PARD3β are independent risk factors for recurrences, with hazard ratio, respectively, of 8.21 (p=0.006) and 3.04 (p=0.029). The latter result was confirmed by the Kaplan-Meier analysis, which evidenced the association between decreased PARD3β mRNA levels and shorter disease-free interval. In conclusion, we demonstrated that the expression of PAR complex components is deregulated in the majority of PTC and there is a general trend towards their reduction in ATC tissues. Moreover, a prognostic value for the PARD3β gene in PTCs is suggested.

Recent findings demonstrated that a subset of papillary thyroid cancers (PTCs) is characterized by reduced expression of the von Hippel-Lindau (VHL) tumor suppressor gene, and that lowest levels associated with more aggressive PTCs. In the present study, the levels of the two VHL mRNA splicing variants, VHL-213 (V1) and VHL-172 (V2), were measured in a series of 96 PTC and corresponding normal matched tissues by means of quantitative RT-PCR. Variations in the mRNA levels were correlated with patients' clinicopathological parameters and disease-free interval (DFI). The analysis of VHL mRNA in tumor tissues, compared to normal matched tissues, revealed that its expression was either up- or down-regulated in the majority of PTC. In particular, V1 and V2 mRNA levels were altered, respectively, in 78 (81.3%) and 65 (67.7%) out of the 96 PTCs analyzed. A significant positive correlation between the two mRNA variants was observed (p < 0.001). Univariate analysis documented the lack of association between each variant and clinicopathological parameters such as age, tumor size, histology, TNM stage, lymph node metastases, and BRAF mutational status. However, a strong correlation was found between altered V1 or V2 mRNA levels and DFI. Multivariate regression analysis indicated higher V1 mRNA values, along with lymph node metastases at diagnosis, as independent prognostic factors predicting DFI. In conclusion, the data reported demonstrate that VHL gene expression is deregulated in the majority of PTC tissues. Of particular interest is the apparent protective role exerted by VHL transcripts against PTC recurrences., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Triple negative breast cancer (TNBC) has an aggressive clinical behaviour, with a poorer prognosis compared to other subtypes. Recently, tumor-infiltrating lymphocytes (TILs) have been proposed as a predictive biomarker for a better clinical outcome and pathological response (pR) after neoadjuvant chemotherapy (NACT) in TNBC. These data confirm the role of the immune system in the neoplastic progression and in the response to therapy. We performed a retrospective analysis of 54 pre-NACT biopsies of TNBC and compared both the percentage of stromal TILs and the degree of PD-L1 expression with the extent of pR to standard NACT. A pathological complete response (pCR) was achieved in 35% of cases. Univariate analysis showed (i) a significant association between PD-L1 expression in ≥25% of neoplastic cells and the achievement of a pCR ( p = 0.024); (ii) a significantly higher frequency of pCR in cases showing ≥50% stromal TILs ( p < 0.001). However in the multivariate analysis only PD-L1 expression on tumor cells remained significantly associated with pCR (OR = 1,13; 95% CI 1,01-1,27), suggesting that the expression of this biomarker could be associated with a subpopulation of TNBC more likely to respond to chemotherapy. These data need to be confirmed by larger studies.

The new Italian cytological classification (2014) of thyroid nodules replaced the TIR3 category of the old classification (2007) with two subclasses, TIR3A and TIR3B, with the aim of reducing the rate of surgery for benign diseases. Moreover, thyroid imaging reporting and data system (TI-RADS) score appears to ameliorate the stratification of the malignancy risk. We evaluated whether the new Italian classification has improved diagnostic accuracy and whether its association with TI-RADS score could improve malignancy prediction. We retrospectively analyzed 70 nodules from 70 patients classified as TIR3 according to the old Italian classification who underwent surgery for histological diagnosis. Of these, 51 were available for cytological revision according to the new Italian cytological classification. Risk of malignancy was determined for TIR3A and TIR3B, TI-RADS score, and their combination. A different rate of malignancy ( p = 0.0286) between TIR3A (13.04%) and TIR3B (44.44%) was observed. Also TI-RADS score is significantly ( p = 0.003) associated with malignancy. By combining cytology and TI-RADS score, patients could be divided into three groups with low (8.3%), intermediate (21.4%), and high (80%) risk of malignancy. In conclusion, the new Italian cytological classification has an improved diagnostic accuracy. Interestingly, the combination of cytology and TI-RADS score offers a better stratification of the malignancy risk.

Prognosis and outcomes of critically ill patients are strictly related with inflammatory status. Inflammation involves a multitude of interactions between different cell types and chemical mediators. Omega-3 polyunsaturated fatty acids (PUFAs), mainly represented by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are able to inhibit different pathways including leukocyte chemotaxis, adhesion molecule expression and interactions, and production of inflammatory cytokines, through the action of specialized proresolving mediators (SPMs). SPMs from omega-6 fatty acids, such as lipoxins, and from omega-3 fatty acids such as resolvins, protectins, and maresins, act in reducing/resolving the inflammatory process in critical diseases, stimulating the phases of resolution of inflammation. In this light, the resolution of inflammation is nowadays considered as an active process, instead of a passive process. In critical illness, SPMs regulate the excessive posttrauma inflammatory response, protecting organs from damage. This review focuses on the role of omega-3 PUFAs as pharma nutrition agents in acute inflammatory conditions, highlighting their effects as anti-inflammatory or proresolving agents.

Background: Breast-conserving surgery (BCS) is considered the gold-standard treatment for early breast cancer. Ultrasound-guided percutaneous biopsy or stereotactic biopsy of a breast lesion allows preoperative histological diagnosis. Various techniques have been proposed for identifying non-palpable breast tumors, but the most popular method is the wire-guided localization (WGL) technique. The aim of this study was to propose an alternative technique for optimizing the WGL procedure, facilitating breast surgery and reducing complications., Patients and Methods: We performed a prospective study on 40 patients with a single non-palpable breast lesion. For the preoperative localization of mammary lesions, patients were divided randomly into two groups: 20 patients underwent conventional WGL technique and 20 underwent 'optimized' personalized technique., Results: In the group treated with the optimized technique, dislocation of the wire occurred in only 2/20 cases, whereas in those with the conventional technique, dislocation occurred in 9/20 cases (p=0.03). In 5/20 cases of the conventional WGL technique, the wire was accidentally cut by the surgeon, whereas no similar complications were observed in the group that underwent the optimized technique (p=0.047). Re-excision of the surgical margins was necessary in 6/20 cases with the conventional technique, while re-excision was not required for any case using the optimized technique (p=0.02)., Conclusion: The proposed optimized technique ensures good esthetic results, enabling the surgeon to identify the lesion and perform oncoplastic breast surgery, and allows surgical time to be reduced., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies.

Background: Nipple-sparing mastectomy (NSM) is a recognized treatment for selected patients with breast cancer (BC). Our study aimed to analyze 7 years' experience in NSM and breast reconstruction for patients with preoperative diagnosis of non-invasive BC., Patients and Methods: All NSMs with breast reconstruction, performed between January 2007 and December 2013 in patients with preoperative diagnosis of non-invasive BC, were considered., Results: Thirty-five NSMs were performed, 23 cases confirming the diagnosis of non-invasive BC, and in 12 patients it also resulted in findings of an invasive component. Patients were stratified into two groups: breast reconstruction was performed i) with silicone definitive implant, ii) with a temporary breast tissue expander. An invasive component at the postoperative histological examination was significantly associated with tissue expander reconstruction (p=0.03)., Conclusion: In selected cases, NSM is a valid and safe procedure. Further critical evaluations are required for more evidence on this argument., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Prone position is used to recruit collapsed dependent lung regions during severe acute respiratory distress syndrome, improving lung elastance and lung gas content. We hypothesised that, in the absence of recruitment, prone position would not result in any improvement in lung mechanical properties or gas content compared to supine position., Methods: Ten healthy pigs under general anaesthesia and paralysis underwent a pressure-volume curve of the respiratory system, chest wall and lung in supine and prone positions; the respective elastances were measured. A lung computed tomography (CT) scan was performed in the two positions to compute gas content (i.e. functional residual capacity (FRC)) and the distribution of aeration. Recruitment was defined as a percentage change in non-aerated lung tissue compared to the total lung weight., Results: Non-aerated (recruitable) lung tissue was a small percentage of the total lung tissue weight in both positions (4 ± 3 vs 1 ± 1 %, supine vs prone, p = 0.004). Lung elastance decreased (20.5 ± 1.8 vs 15.5 ± 1.6 cmH2O/l, supine vs prone, p < 0.001) and functional residual capacity increased (380 ± 82 vs 459 ± 60 ml, supine vs prone, p = 0.025) in prone position; specific lung elastance did not change (7.0 ± 0.5 vs 6.5 ± 0.5 cmH2O, supine vs prone, p = 0.24). Lung recruitment was low (3 ± 2 %) and was not correlated to increases in functional residual capacity (R (2) 0.2, p = 0.19). A higher amount of well-aerated and a lower amount of poorly aerated lung tissue were found in prone position., Conclusions: In healthy pigs, prone position ameliorates lung mechanical properties and increases functional residual capacity independently from lung recruitment, through a redistribution of lung aeration.

Background: High tidal volume can cause ventilator-induced lung injury (VILI), but positive end-expiratory pressure (PEEP) is thought to be protective. We aimed to find the volumetric VILI threshold and see whether PEEP is protective per se or indirectly., Methods: In 76 pigs (22 ± 2 kg), we examined the lower and upper limits (30.9-59.7 mL/kg) of inspiratory capacity by computed tomography (CT) scan at 45 cmH2O pressure. The pigs underwent a 54-h mechanical ventilation with a global strain ((tidal volume (dynamic) + PEEP volume (static))/functional residual capacity) from 0.45 to 5.56. The dynamic strain ranged from 18 to 100 % of global strain. Twenty-nine pigs were ventilated with end-inspiratory volumes below the lower limit of inspiratory capacity (group "Below"), 38 within (group "Within"), and 9 above (group "Above"). VILI was defined as death and/or increased lung weight., Results: "Below" pigs did not develop VILI; "Within" pigs developed lung edema, and 52 % died before the end of the experiment. The amount of edema was significantly related to dynamic strain (edema 188-153 × dynamic strain, R (2) = 0.48, p < 0.0001). In the "Above" group, 66 % of the pigs rapidly died but lung weight did not increase significantly. In pigs ventilated with similar tidal volume adding PEEP significantly increased mortality., Conclusions: The threshold for VILI is the lower limit of inspiratory capacity. Below this threshold, VILI does not occur. Within these limits, severe/lethal VILI occurs depending on the dynamic component. Above inspiratory capacity stress at rupture may occur. In healthy lungs, PEEP is protective only if associated with a reduced tidal volume; otherwise, it has no effect or is harmful.

Background: The spread of mammographic screening programs has allowed an increasing amount of early breast cancer diagnosis. A modern approach to non-palpable breast lesions requires an accurate intraoperative localization, in order to achieve a complete surgical resection. In addiction, the assessment of lymph node status is mandatory as it represents a major prognostic factor in these patients. The aim of this study is to evaluate the reliability of a modified technical approach using a single nanocolloidal radiotracer to localize both sentinel node and breast occult lesion., Methods: Twenty-five patients with a single non-palpable breast lesions and clinically negative axilla were enrolled. In the same day of surgery, patients underwent intratumoral and peritumoral administration of (99m)Tc-labeled nanocolloid tracer under sonographic guidance. A lymphoscintigraphy was performed to localize the sentinel lymph node and its cutaneous projection was marked on the skin in order to guide the surgeon to an optimal incision. During surgery an hand-held gamma-detection probe was used to select the best surgical access route and to guide localization of both occult breast lesion and sentinel lymph node. After specimen excision, the surgical field was checked with the gamma-probe to verify the absence of residual sources of significant radioactivity, thereby ensuring a radical treatment in a single surgical session and minimizing normal tissue excision., Results: Both targeted breast lesion and sentinel lymph node were localized and removed at the first attempt in every patients and histopathological diagnosis of malignancy was confirmed in 25/26 samples. Non-palpable lesions were included within the surgical margins in all patients and in all samples surgical margins were free from neoplastic infiltration thus avoiding any further reintervention. Only two patients showed metastatic involvement of sentinel lymph node., Conclusions: The modified sentinel node and occult lesion localization (SNOLL) technique performed with a single injection of nanocolloidal radiotracer has shown an excellent intraoperative identification rate of both non-palpable lesion and sentinel lymph node. This procedure offers, as opposed to standard techniques, an accurate, simple and reliable approach to the management of non-palpable breast cancer.

Background: Primitive sarcoma of the breast is a rare and challenging disease at high risk of recurrence and with poor prognosis. There are controversies in the diagnosis and management of such solid tumor due to its rarity and heterogeneity. This sarcoma is poorly responsive to both chemotherapy and radiotherapy, thus, surgery is the first and most important therapeutic approach. However, given the rarity of this type tumor it has not be possible to standardize unique guidelines for the proper surgical strategy to adopt. Here, we performed a retrospective study of new 10 cases of primitive sarcoma of the breast that underwent either mastectomy or a more conservative quadrantectomy, in the attempt to better standardize correct surgical indications., Methods: Ten new cases of primitive sarcoma of the breast were registered between 2002 and 2012 and constituted the study group. They underwent either mastectomy or quadrantectomy and the clinical, prognostic and survival characteristics after surgery were analysed., Results: Within the group of patients treated with mastectomy, two had metastasis and died because of that. Among the five patients treated with quadrantectomy four are alive and free of disease after 3 to 5 years follow-up, while the patient with sarcoma arising in pregnancy, although is still alive, developed lung metastases four years after surgery., Conclusions: The first and most important therapeutic approach to primary sarcomas of the breast is surgical which has the purpose to achieve radical tumor excision to prevent local recurrence and skip metastases. However, given the rarity of the condition and the consequent small number of cases in this, like in similar studies, it is not possible to draw any definitive conclusions and further studies with larger numbers are necessary. However it would appear that performing a larger procedure such as mastectomy rather than performing a more limited one such as a quadrantectomy, has no advantage in terms of overall prognosis.

Aim: The study of sentinel lymph node has greatly increased the knowledge about lymphatic drainage in breast cancer., Material of Study: The experience of 181 patients operated for breast carcinoma in the last two years, of which 70 undergoing SLN biopsy, allowed us to highlight some peculiarities of lymphatic drainage of the breast and led us to physiological and pathological considerations about lymphatic flow in patients for breast carcinoma. We studied patients undergoing lymphoscintigraphic mapping with SLN biopsy who were candidates for breast cancer surgery., Results: Searching for SLN's location, we found that in 88.6% cases the SLN was at level I, in 8.6% it was at level II, in no case it was at level III and in 2.8% we found lymphatic drainage to the contralateral axilla., Discussion: Thanks to this dynamic study we were able to highlight a preferential subcutaneous lymphatic path from the breast parenchyma reaching the contralateral axilla, crossing anteriorly the thorax. Literature review showed CAM incidence ranges from 3.6% to 6% and can be caused by occult primary cancer of the contralateral breast, contralateral spread of breast cancer and presence of another kind of tumor., Conclusions: The presence of contralateral axillary metastasis, although known, allowed us to scintigrafically document (for the first time) the pathway of an alternative lymph flow and to suppose the possible causes. Thanks to this observation, considerations can be drawn about clinical, pathophysiological and oncological implications, with an impact on post-operative follow-up.

Objective: To describe and compare the decisions critical for survival or quality of life [critical decisions (CDs)] made for patients with advanced dementia in nursing homes (NHs) and home care (HC) services., Design: Prospective cohort study with a follow-up of 6 months., Setting: Lombardy Region (NHs) and Reggio-Emilia and Modena Districts (HC), Italy., Participants: Patients (496 total; 315 in NHs and 181 in HC) with advanced dementia (Functional Assessment Staging Tool score ≥ 7) and expected survival ≥ 2 weeks., Measurements: At baseline, the patients' demographic data, date of admission and of dementia diagnosis, type of dementia, main comorbidities, presence of pressure sores, ongoing treatments, and current prescriptions were abstracted from clinical records. At baseline and every 15 days thereafter, information regarding the patients' general condition and CDs (deemed critical by the doctor or team) was collected by an interview with the doctor. For each CD, the physician reported the problem that led to the decision, that was eventually made, the purpose of the decision, whether the decision had been discussed with and/or communicated to the family, who made the final decision, whether the decision was maintained after 1 week, whether it corresponded to what the doctor would have judged appropriate, and the expected survival of the patient (≤ 15 days)., Results: For 267 of the 496 patients (53.8%; 60.3% in NHs and 42.5% at home), 644 CDs were made; for 95 patients, more than 1 CD was made. The problems that led to a CD were mainly infections (respiratory tract and other infections; 46.6%, 300/644 CDs); nutritional/hydration problems (20.6%; 133 CDs); and the worsening of a pre-existing disease (9.3%; 60 CDs). The most frequent type of decision concerned the prescription of antibiotics (overall 41.1%, 265/644; among NH patients 44.6%, 218/488; among HC patients, 30.2%, 47/156). The decision to hospitalize the patient was more frequently reported for HC than NH patients (25.5% vs 3.1%). The most frequent purposes of the CDs in both settings were reducing symptoms or suffering (more so in NHs; 81.1% vs 57.0% in HC) and prolonging survival (NH 27.5%; HC 23.1%; multiple purposes were possible). For 26 decisions (3.8%), the purpose was to ease death or not to prolong life., Conclusions: Decisions critical for the survival or quality of life of patients with advanced dementia were made for approximately one-half of the patients during a 6-month time frame, and such decisions were made more frequently in NHs than in HC. HC patients were more frequently hospitalized, and a sizeable minority of these patients were treated with the goal of prolonging survival. Italian patients with advanced dementia may benefit from the implementation of palliative care principles, and HC patients may benefit from the implementation of measures to avoid hospitalizing patients near the end of life., (Copyright © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Breast neoplasms are one of the leading causes of morbidity and mortality in women. Even if surgery is the treatment of choice, other forms of less invasive radical treatment are desirable. High-intensity focused ultrasound is already established as a valid non-invasive technique that ensures tumor ablation in various organs. The use of ultrasound or magnetic resonance guidance allows having some advantages such as the capability to treat tumors in moving organs or the possibility to have a real-time monitoring of the temperature increase. The aim of this paper is to report the use of high-intensity focused ultrasound technique with ultrasound and magnetic resonance guidance for the ablation of breast tumors, including both benign and malignant lesions.

The authors report the personal experience of some patients undergoing surgery for carcinoma of Merkel and discuss the diagnosis and therapeutic approach guided by literature and international guidelines. Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumour, which prefers the Caucasian race in adulthood. Approximately 78% of patients are over than 59 years, the most common location is at the level of the head and neck (50.8%) and less frequently in the limbs (33.7%). The literature is discordant about the causes and risk factors for this cancer. In fact, some authors describe major risk factor the immunosoppression, still others see prolonged exposition to UV radiation increases the risk for the onset of this tumor. Metastasizes early to the skin (28%), the lymph nodes (27%), liver (13%), lung (10%), bone (10%) and encephalon (6%), and may recur both locally (30-60%) and both locoregional (40-73%). Our experience confirms the difficulty of preoperative clinical diagnosis and a correct therapeutic approach to Merkel cell carcinoma for the lack of specific characteristics as first clinical assessment, which may keep the suspect nature. International guidelines provide a wide excision (3 cm in largeness and 2 cm in depth) to reduce the risk of disease recurrence, preferring adjuvant chemotherapy not radiotherapy. For lesions of stage I-II over the wide excision also regional lymphadenectomy is performed or, more rarely, the technique of sentinel lymph node.

Unlabelled: The contralateral axillary lymph node metastasis (CAM) from breast cancer are very rare, and pose a number of classification problems and therefore also on the surgery attitude to be adopted and the subsequent surgical oncological approach, making a distinction between synchronous and metachronous cases. You must always wait for a reasonable period of time to exclude the presence of an occult cancer in the contralateral breast. You make assumptions about the lymphatic pathways that determine this metastasis underlining that in the literature (rare) cases are reported in which the lymphoscintigraphic sentinel lymph node search has shown an uptake of contralateral axillary lymph nodes., Key Words: Breast cancer, Controlateral axillary lymph node metastasis, Lymph node metastasis.

Background: Adipose tissue is a source of stromal and vascular cells suitable for regenerative medical applications. Cell recovery depends on several factors, including the characteristics of the cannula used to harvest tissue., Objectives: The authors assess whether aspiration of superficial layers of adipose tissue performed with a microcannula, rather than a standard cannula, allows for improved isolation of stromal and vascular cells, and they evaluate the angiogenic potential of the isolated cells in vitro and in vivo., Methods: Adipose-derived stromal and stem cells (ADSC) were collected from the lipoaspirate of the abdomen and hip regions of 6 healthy female donors. For adipose tissue harvest, several options were compared: (1) a rounded-tip cannula with a length of 170 mm, a diameter of 3 mm, and a single elliptic suction port on the side near its distal end (port diameter: 3 × 9 mm) or (2) a rounded-tip infiltration cannula with a length of 170 mm, a diameter of 2 mm, and 5 round ports placed spirally along the sides of the distal cannula shaft (each port diameter: 1 mm) (Shipper Medical Technologies Corporation, Centennial, Colorado). Isolated cells were characterized for (1) expression of the endothelial specific marker CD31 by immunohistochemical and cytofluorimetric analyses and (2) tubular-like structure formation using a 3-dimensional angiogenesis assay on Matrigel. Human ADSC were transduced to express firefly luciferase as a marker suitable for bioluminescent tracking and transplantation studies into immunosuppressed mice were performed., Results: ADSC yield was determined to be significantly higher in samples collected with the microcannula (P = .04). Moreover, isolated cells acquired typical endothelial-like morphology in vitro, formed capillary-like structures, and expressed the distinctive endothelial cell marker CD31. Cells implanted into immunosuppressed mice persisted for several weeks in areas undergoing neovascularization., Conclusions: These results suggest that aspiration of adipose tissue with a microcannula can be a minimally invasive method to obtain clinically relevant numbers of stromal and vascular cells useful for autologous transplant procedures and for promoting tissue regeneration and neovascularization.

The word "adenomatous hyperplasia of rete testis" (AHRT) was used by M. Nistal et Al. for the first time in an article about the cystic dysplasia of the testis (1976). AHRT is a benign lesion of the testis. The patient who came to our attention was studied with a testicular echo color Doppler that identified a solid, well circumscribed and hypoechoic mass of 4.5 x3.8mm as diameter, localized in the upper third of the right testicle and with a perilesional vascularization pattern. The preoperative study was based on an accurate medical history, on an ultrasound with contrast and on a RMI. The treatment consisted in an echo guided excisional biopsy of the testicular lesion, considering this as the best approach for those testicular neoformation difficult to define, with a lot of benefits for the patients, especially for those monorchid.

Introduction: Healthy piglets ventilated with no positive end-expiratory pressure (PEEP) and with tidal volume (VT) close to inspiratory capacity (IC) develop fatal pulmonary oedema within 36 h. In contrast, those ventilated with high PEEP and low VT, resulting in the same volume of gas inflated (close to IC), do not. If the real threat to the blood-gas barrier is lung overinflation, then a similar damage will occur with the two settings. If PEEP only hydrostatically counteracts fluid filtration, then its removal will lead to oedema formation, thus revealing the deleterious effects of overinflation., Methods: Following baseline lung computed tomography (CT), five healthy piglets were ventilated with high PEEP (volume of gas around 75% of IC) and low VT (25% of IC) for 36 h. PEEP was then suddenly zeroed and low VT was maintained for 18 h. Oedema was diagnosed if final lung weight (measured on a balance following autopsy) exceeded the initial one (CT)., Results: Animals were ventilated with PEEP 18 ± 1 cmH2O (volume of gas 875 ± 178 ml, 89 ± 7% of IC) and VT 213 ± 10 ml (22 ± 5% of IC) for the first 36 h, and with no PEEP and VT 213 ± 10 ml for the last 18 h. On average, final lung weight was not higher, and actually it was even lower, than the initial one (284 ± 62 vs. 347 ± 36 g; P = 0.01)., Conclusions: High PEEP (and low VT) do not merely impede fluid extravasation but rather preserve the integrity of the blood-gas barrier in healthy lungs.

Objective: Tidal volume (VT) and volume of gas caused by positive end-expiratory pressure (VPEEP) generate dynamic and static lung strains, respectively. Our aim was to clarify whether different combinations of dynamic and static strains, resulting in the same large global strain, constantly produce lung edema., Design: Laboratory investigation., Setting: Animal unit., Subjects: Twenty-eight healthy pigs., Interventions: After lung computed tomography, 20 animals were ventilated for 54 hours at a global strain of 2.5, either entirely dynamic (VT 100% and VPEEP 0%), partly dynamic and partly static (VT 75-50% and VPEEP 25-50%), or mainly static (VT 25% and VPEEP 75%) and then killed. In eight other pigs (VT 25% and VPEEP 75%), VPEEP was abruptly zeroed after 36-54 hours and ventilation continued for 3 hours., Measurements and Main Results: Edema was diagnosed when final lung weight (balance) exceeded the initial weight (computed tomography). Mortality, lung mechanics, gas exchange, pulmonary histology, and inflammation were evaluated. All animals ventilated with entirely dynamic strain (VT 825±424 mL) developed pulmonary edema (lung weight from 334±38 to 658±99 g, p<0.01), whereas none of those ventilated with mainly static strain (VT 237±21 mL and VPEEP 906±114 mL, corresponding to 19±1 cm H2O of positive end-expiratory pressure) did (from 314±55 to 277±46 g, p=0.65). Animals ventilated with intermediate combinations finally had normal or largely increased lung weight. Smaller dynamic and larger static strains lowered mortality (p<0.01), derangement of lung mechanics (p<0.01), and arterial oxygenation (p<0.01), histological injury score (p=0.03), and bronchoalveolar interleukin-6 concentration (p<0.01). Removal of positive end-expiratory pressure did not result in abrupt increase in lung weight (from 336±36 to 351±77 g, p=0.51)., Conclusions: Lung edema forms (possibly as an all-or-none response) depending not only on global strain but also on its components. Large static are less harmful than large dynamic strains, but not because the former merely counteracts fluid extravasation.

Aim: evaluate emergency treatment of patients presenting with anaplastic thyroid cancer with acute compressive sympthoms., Material of Study: In the present report, we describe three patients with anaplastic thyroid cancer who presented clinically with acute compressive sympthoms. All patients underwent debulking surgery in order to relieve the sympthoms and perform a potentially curative resection., Results: The first two patients with diagnosis of ATC couldn't undergo to radiotherapy and chemotherapy for the presence of infection of the wound and for the earlier disease relapse in the mediastinum and died after 1 month and 3 months. The third patient (with papillary thyroid cancer with focal areas of anaplastic cancer) after surgical treatment underwent external radiotherapy and is alive over 2 years., Discussion: Compression, deviation, and infiltration of trachea have impeded the achievement of a safe respiratory access with tracheostomy and these three patients underwent debulking surgery to relieve compressive sympthoms. These three cases confirm the importance of acute local compressive symptoms of ATC and their difficult management., Conclusions: In such cases a debulking surgery can be considered as a valid option in the emergency management. Nevertheless debulking surgery (and even radical excision of the tumor), when performed alone, offer a minimal improved survival.

Sarcoma of the breast is a rare condition, with one possible meaning of relapse ad metastastasize, and behaves biologically as a stromal tumor. Surgery is the first choise and mastectomy is the best procedure adopted in these tumors. The aim of our study was to assess diagnostic and treatment options for PT, based on a review of the literature and our experience with a case of breast sarcoma arising from a phyllodes tumor.

Sarcoma of the breast is a rare and heterogeneous lesion. We describe a case of a patient surgically treated for a breast lesion during pregnancy. The lesion resulted in a concentric neoplasia with the histological features of high grade sarcoma growing in a phyllodes tumor which was at the time grown in a fibroadenoma. Key words: Breast sarcoma, Non-epithelial breast tumour, Phillode, Pregnancy.

Introduction: Hepatic mitochondrial dysfunction may play a critical role in the pathogenesis of metformin-induced lactic acidosis. However, patients with severe metformin intoxication may have a 30 to 60% decrease in their global oxygen consumption, as for generalized inhibition of mitochondrial respiration. We developed a pig model of severe metformin intoxication to validate this clinical finding and assess mitochondrial function in liver and other tissues., Methods: Twenty healthy pigs were sedated and mechanically ventilated. Ten were infused with a large dose of metformin (4 to 8 g) and five were not (sham controls). Five others were infused with lactic acid to clarify whether lactic acidosis per se diminishes global oxygen use. Arterial pH, lactatemia, global oxygen consumption (VO2) (metabolic module) and delivery (DO2) (cardiac output by thermodilution) were monitored for nine hours. Oxygen extraction was computed as VO2/DO2. Activities of the main components of the mitochondrial respiratory chain (complex I, II and III, and IV) were measured with spectrophotometry (and expressed relative to citrate synthase activity) in heart, kidney, liver, skeletal muscle and platelets taken at the end of the study., Results: Pigs infused with metformin (6 ± 2 g; final serum drug level 77 ± 45 mg/L) progressively developed lactic acidosis (final arterial pH 6.93 ± 0.24 and lactate 18 ± 7 mmol/L, P < 0.001 for both). Their VO2 declined over time (from 115 ± 34 to 71 ± 30 ml/min, P < 0.001) despite grossly preserved DO2 (from 269 ± 68 to 239 ± 51 ml/min, P = 0.58). Oxygen extraction accordingly fell from 43 ± 10 to 30 ± 10% (P = 0.008). None of these changes occurred in either sham controls or pigs infused with lactic acid (final arterial pH 6.86 ± 0.16 and lactate 22 ± 3 mmol/L). Metformin intoxication was associated with inhibition of complex I in the liver (P < 0.001), heart (P < 0.001), kidney (P = 0.003), skeletal muscle (P = 0.012) and platelets (P = 0.053). The activity of complex II and III diminished in the liver (P < 0.001), heart (P < 0.001) and kidney (P < 0.005) while that of complex IV declined in the heart (P < 0.001)., Conclusions: Metformin intoxication induces lactic acidosis, inhibits global oxygen consumption and causes mitochondrial dysfunction in liver and other tissues. Lactic acidosis per se does not decrease whole-body respiration.

Aim: Presentation of a personal technique for the treatment of perineal fistulas in outpatients., Material of Study: 17 patients with complete non-complex linear intersphincteric or trans-sphincteric fistulas were treated with this technique. First we facilitated the cannulation, then we used the same catheters to place the "seton". We had to use a more subtle and smooth, rugged nylon thread, instead of the floss, due to the difference between the large size of the silk thread and the small lumen of the cannula., Results: The elastic traction has determined not only a valid mean of capillary drainage, but also a rapid passage through the tissues without any functional impairment, in times ranging from 2 to 4 weeks., Discussion: The traditional surgery is burdened by a significant number of relapses . This is due to the anatomical characteristics of the anal canal, to the difficulty to ensure the integrity of the sphincteric structures and to the position of the fistula. It's essential to identify the whole extension of the fistula to avoid it's partial removal and the persistence of granulation tissue therefore. With our technique, we got a good drainage of the fistula, avoiding to leave any residues or to create false paths causing relapses as may happen with the explorers., Conclusions: The discomfort suffered by patients was minimal and the results achieved led us to support a greater diffusion of this technique in outpatients.