Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC).

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. MATERIAL AND METHODS: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. RESULTS: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. CONCLUSIONS: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials.

Low neutrophil-to-lymphocyte ratio and pan-immune-inflammation-value predict nodal pathologic complete response in 1274 breast cancer patients treated with neoadjuvant chemotherapy: a multicenter analysis.

Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings. Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients. Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units. Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR. Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51-0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44-0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)-/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12-0.83; p = 0.02) and ER-/HER2- (OR = 0.41; 95% CI, 0.17-0.97; p = 0.04) BC patients. Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC. Registration: Eudract number NCT05798806.

Efficacy of bi-level erector spinae plane block versus bi-level thoracic paravertebral block for postoperative analgesia in modified radical mastectomy: a prospective randomized comparative study.

BACKGROUND: Postoperative analgesia in breast surgery is difficult due to the extensive nature of the surgery and the complex innervation of the breast; general anesthesia can be associated with regional anesthesia techniques to control intra- and post-postoperative pain. This randomized comparative study aimed to compare the efficacy of the erector spinae plane block and the thoracic paravertebral block in radical mastectomy procedures with or without axillary emptying. METHODS: This prospective randomized comparative study included 82 adult females who were randomly divided into two groups using a computer-generated random number. Both groups, Thoracic Paraverterbal block group and Erector Spinae Plane Block group (41 patients each), received general anesthesia associated with a multilevel single-shot thoracic paravertebral block and a multilevel single-shot erector spinae plane block, respectively. Postoperative pain intensity (expressed as Numeric Rating Scale), patients who needed rescue analgesic, intra- and post-operative opioid consumption, post-operative nausea and vomiting, length of stay, adverse events, chronic pain at 6 months, and the patient's satisfaction were recorded. RESULTS: At 2 h (p < 0.001) and 6 h (p = 0.012) the Numeric Rating Scale was significantly lower in Thoracic Paraverterbal block group. The Numeric Rating Scale at 12, 24, and 36 postoperative hours did not show significant differences. There were no significant differences also in the number of patients requiring rescue doses of NSAIDs, in intra- and post-operative opioid consumption, in post-operative nausea and vomiting episodes and in the length of stay. No failures or complications occurred in the execution of techniques and none of the patients reported any chronic pain at six months from the surgery. CONCLUSIONS: Both thoracic paravertebral block and erector spinae plane block can be effectively used in controlling post-mastectomy pain with no significant differences between the two blocks. TRIAL REGISTRATION: The study was prospectively registered on Clinicaltrials.gov (trial identifier NCT04457115) (first registration 27/04/2020).

Oligometastatic breast cancer and metastasis-directed treatment: an aggressive multimodal approach to reach the cure.

Metastatic breast cancer (BC) is considered an incurable disease and is usually treated with palliative intent. However, about 50% of metastatic BCs present with only a few metastatic lesions and are characterized by longer overall survival. These patients, defined as oligometastatic, could benefit from a multimodal approach, which combines systemic therapy with metastasis-directed treatment (stereotactic ablative therapy or surgery). The current definition of oligometastatic seems incomplete since it is based only on imaging findings and does not include biological features, and the majority of relevant data supporting this strategy comes from retrospective or non-randomized studies. However, the chance of reaching long-term complete remission or even a cure has led to the development of randomized trials investigating the impact of combined treatment in oligometastatic BC (OMBC). The SABR-COMET trial, the first randomized study to include BC patients, showed promising results from a combination of stereotactic ablative radiotherapy and systemic therapy. Considering the randomized trial's results, multidisciplinary teams should be set up to select OMBC patients who could achieve long-term survival with aggressive multimodal treatment.

Locoregional treatment of de novo stage IV breast cancer in the era of modern oncology.

Approximately 6% of metastatic breast cancers arise de novo. While systemic therapy (ST) remains the treatment backbone as for patients with metachronous metastases, locoregional treatment (LRT) of the primary tumor remains a controversial method. The removal of the primary has an established role for palliative purposes, but it is unclear if it could also determine a survival benefit. Retrospective evidence and pre-clinical studies seem to support the removal of the primary as an effective approach to improve survival. On the other hand, most randomized evidence suggests avoiding LRT. Both retrospective and prospective studies suffer several limitations, ranging from selection bias and outdated ST to a small sample of patients. In this review we discuss available data and try to identify subgroups of patients which could benefit the most from LRT of the primary, to facilitate clinical practice decisions, and to hypothesize future studies design on this topic.

Neoadjuvant endocrine therapy for luminal breast tumors: State of the art, challenges and future perspectives.

Neoadjuvant endocrine treatment (NET) associates to satisfactory rates of breast conservative surgery and conversions from inoperable to operable hormone receptor-positive (HR+)/HER2-negative breast cancer (BC), with less toxicities than neoadjuvant chemotherapy (NACT) and similar outcomes. Hence, it has been proposed as a logical alternative to NACT in patients with HR+/HER2- BC candidate to a neoadjuvant approach. Nevertheless, potential barriers to the widespread use of NET include the heterogeneous nature of patient response coupled with the long duration needed to achieve a clinical response. However, interest in NET has significantly increased in the last decade, owing to more in-depth investigation of several biomarkers for a more adequate patient selection and on-treatment benefit monitoring, such as PEPI score, Ki67 and genomic assays. This review is intended to describe the state-of-the-art regarding NET, its future perspectives and potential integration with molecular biomarkers for the optimal selection of patients, regimen and duration of (neo)adjuvant treatments.

Successful retrieval of a needle point from the breast through a vacuum-assisted breast biopsy system.

Stereotactic vacuum-assisted breast biopsy (VABB) system is generally used to perform breast biopsies after identifying suspicious lesions that are occult on ultrasound. In this case, we used an 8-Gauge VABB to retrieve a needle point retained in the outer-lower quadrant of the right breast of a patient previously treated with lumpectomy. The use of stereotactic VABB system in this specific clinical setting has been never described before and resulted minimally invasive and perfectly suitable for correct localisation and retrieval of the 3-mm needle point; moreover, it may be easily reproduced elsewhere.

Local treatment in patients with hereditary breast cancer: decision-making process in low-, moderate-, high-penetrance pathogenic germline mutation carriers.

PURPOSE OF REVIEW: We summarize recent evidence regarding commonly tested breast cancer susceptibility genes and review indications derived from recently published guidelines regarding management of carriers affected by early breast cancer (BC). RECENT FINDINGS: Management of affected women with a known genetic predisposition to BC was matter of debate at the most relevant international conferences, such as St. Gallen International Consensus Conference and San Antonio Breast Cancer Symposium held both in 2021. At the same time, a joint Experts Panel from American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Surgical Oncology (ASCO/ASTRO/SSO) convened to develop recommendations to support clinical decision-making in this specific setting and results about administration of new systemic therapies such as poly adenosine diphosphate-ribose polymerase (PARP) inhibitors became available. SUMMARY: Population of patients affected by BC and carriers of mutations in susceptibility genes is progressively increasing, but new mutations identified do not always have a clear clinical impact.To date, we have data to support consideration of different local management choices for affected patients carrying specific mutations, but some issues especially relating to breast-conserving surgery or administration of radiotherapy in these patients, still need to be better addressed. Opinions about the best way to treat these patients are still heterogeneous and information deriving from different sources seems to be conflicting at times. Our purpose is to offer a synopsis of the different evidence available that may be helpful in clinical decision making.

Comparison of Ferric Sodium EDTA in Combination with Vitamin C, Folic Acid, Copper Gluconate, Zinc Gluconate, and Selenomethionine as Therapeutic Option for Chronic Kidney Disease Patients with Improvement in Inflammatory Status.

Anemia is one of the most frequent and earliest complications of chronic kidney disease (CKD), which impacts a patient's quality of life and increases the risk of adverse clinical outcomes. Patients' inflammatory status is strictly related to the occurrence of functional iron deficiency anemia (IDA) because this causes an increase in hepcidin levels with the consequent inhibition of iron absorption and release from cellular stores into blood circulation. The aim of this study was to evaluate the use of the new oral formulation based on ferric sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate, and selenomethionine (Ferachel Forte®) in patients with moderate CKD and functional IDA, analyzing the inflammatory status in addition to iron blood parameters, in comparison with oral ferrous sulfate and liposomal iron therapies. Sixty-two elderly patients were randomly allocated to one of the following oral treatments for 6 months: ferrous sulfate (Group 1; N = 20), ferric sodium EDTA in combination (Group 2; N = 22), and ferric liposomal formulation (Group 3; N = 20). The evaluated parameters included iron profile parameters of hemoglobin (Hb), sideremia, ferritin, transferrin saturation, C-reactive protein (CRP), and hepcidin. The results showed that in Group 1, there were no improvements. In Group 2, there were statistically significant (p < 0.001) improvements in all evaluated parameters. Finally, in Group 3, there were significant improvements in all evaluated parameters except for hepcidin, which was less than that of Group 2 patients. In conclusion, the findings showed the superior efficacy of the formulation based on ferric sodium EDTA over the other oral iron sources, and that this formulation can contribute to reducing the systemic inflammatory status in patients with CKD.

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients.

BACKGROUND: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. PATIENTS AND METHODS: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). RESULTS: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75-0.80). After external validation the accuracy of the nomogram was confirmed. CONCLUSION: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.

The First Use of Human-Derived ADM in Prepectoral Direct-to-Implant Breast Reconstruction after Skin-Reducing Mastectomy.

INTRODUCTION: Large and ptotic breasts always represented a great reconstructive challenge for plastic surgeons. In order to deal with these patients, we started performing Wise-pattern skin-reducing mastectomies (SRM) followed by direct-to-implant breast reconstructions (DTI-BR) in the prepectoral space where the implants were covered with the autologous adipo-dermal flap and a human acellular dermal matrix called MODA. MATERIALS AND METHOD: We retrospectively reviewed all patients that underwent Wise-pattern SRM followed by MODA-assisted, prepectoral, DTI-BR between January 2017 and November 2019 at our Institution. Inclusion criteria were large ptotic breast and pinch test >2cm, while exclusion criteria were smoking >10 cigarettes/day, history of prior radiotherapy, patients supposedly requiring breast implants bigger than 550cc or post-mastectomy radiotherapy. Patients' data were collected through their electronic medical records. Both short- and long-term outcomes were reported. RESULTS: Seventeen patients underwent Wise-pattern SRM followed by MODA-assisted, prepectoral, DTI-BR for a total of twenty-one breast reconstruction and fourteen matching procedures. Mean follow-up was 13.4 months (SD= ±3.67). No major complication was reported. Three (14.3%) reconstructed breasts had minor complications: 2 (9.5%) minimal (<1cm2) wound dehiscence and 1 (4.8%) de-epithelization of the skin at the T junction that were treated conservatively. Drainages gave mean output of 410.59 ml (SD= ±214.83) and were kept in place on average for 8.59 days (SD= ±3.45). CONCLUSION: Few are the reports in the literature regarding DTI-BR following SRM and even fewer are those where BR was performed in the prepectoral space. Our work demonstrated the safety of prepectoral DTI-BR following SRM in selected patients in accordance with the "conservative reconstruction" principles. Furthermore, we confirmed the reliability of MODA in accordance with previously published works. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer.

BACKGROUND: The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity. PATIENTS AND METHODS: This multi-center, single-arm, two-stage phase II trial, assessed the safety and the activity of a new treatment regimen for HER2-positive, early or locally advanced breast cancer. Patients received six 21-day cycles of non-pegylated liposomal doxorubicin, 50 mg/m2 intravenously (i.v.) on day 1, docetaxel, 30 mg/m2 i.v. on days 2 and 9, trastuzumab, 2 mg/kg/week i.v. on days 2, 9, and 16 (with 4 mg/kg loading dose), in association with metformin 1000 mg orally twice daily. The primary endpoint was the rate of pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). A subgroup of patients performed a 3-deoxy-3-18F-fluorothymidine positron emission tomography (FLT-PET) at baseline and after one cycle. RESULTS: Among 47 evaluable patients, there were 18 pCR [38.3%, 95% confidence interval (CI) 24.5-53.6%]. A negative estrogen-receptor status, high Ki67, and histological grade 3 were related with pCR, although only grade reached statistical significance. FLT-PET maximum standardized uptake value after one cycle was inversely related to pCR in the breast (odds ratio 0.29, 95% CI 0.06-1.30, p = 0.11). Toxicity included grade 3-4 neutropenia in 70% and febrile neutropenia in 4% of patients, grade 1-2 nausea/vomiting in 60%/38%, and grade 3 in 4%/2%, respectively, grade 1-2 diarrhea in 72%, and grade 3 in 6%. There were two cases of reversible grade 2 left-ventricular ejection-fraction decrease, and one case of sharp troponin-T increase. CONCLUSIONS: The concomitant administration of trastuzumab, liposomal doxorubicin, docetaxel, and metformin is safe and shows good activity, but does not appear to improve activity over conventional sequential regimens.

Sub-muscular Reconstruction after NAC Sparing Mastectomy: Direct to Implant Breast Reconstruction with Human ADM Versus Tissue Expander.

BACKGROUND: Nipple areola complex (NAC) sparing mastectomy allows good oncological and aesthetic results. The study compares the results, in terms of self-evaluated satisfaction and symmetry, of direct to implant (DTI) sub-muscular breast reconstruction, with the aid of human acellular dermal matrix (ADM) versus two-stage reconstruction with sub-muscular tissue expander, followed by implant. MATERIALS AND METHODS: This is a retrospective, observational, single-center, non-randomized, case-control study. Inclusion criteria were: unilateral NAC sparing mastectomy at Forlì Hospital between 2014 and 2018; sub-muscular reconstruction; minimum follow-up of 12 months from the reconstructive stage; no history of radiotherapy. Patients were divided into two groups: group A included patients who underwent DTI breast reconstruction with the aid of human ADM; group B were those who underwent a two-stage reconstruction with tissue expander then implant. We collected data on: (1) Self-evaluated satisfaction by Breast Q questionnaire (scores from 0 to 100). (2) Observer-evaluated symmetry. Bi-dimensional photographs were collected and evaluated by 11 breast surgeons blinded to each other, who assigned a score for symmetry (from 0 to 10). (3) Symmetry of anthropometric measures collected by hand and volume estimated by Breast V application. RESULTS: Group A included 28 patients; group included B 26 patients. Breast-Q questionnaires reported the following results: satisfaction with breasts in group A 65 ± 12 versus group B 68 ± 14; satisfaction with outcome in group A 88 ± 16 versus group B 93 ± 11; psychosocial well-being in group A 71 ± 20 versus group B 76 ± 17; sexual well-being in group A 63 ± 26 versus group B 60 ± 13; physical well-being in group A 68 ± 15 versus group B 60 ± 12. The average symmetry breast score assigned to group A was 6.9, versus group B 7.2. Regarding the anthropometric measures in group A, the differences between right and left were major to those in group B. Regarding breast volume, the mean difference between right and left in group A was 31.89 cc ± 24.97, whereas in group B was 25.46 cc ± 23.59. CONCLUSION: Our data show better symmetry and better psychosocial well-being in the two-stage reconstruction, and higher satisfaction with sexual and physical well-being in DTI reconstructions. These aspects should be discussed with the patient while collecting the informed consent. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

"Bifidus pedicle", The Use of Bilobed Superomedial Pedicle for Breast Reshaping Following Upper Outer Quadrantectomy: A New Oncoplastic Breast Surgery Technique.

INTRODUCTION: The aim of this work was to describe our technique, the "Bifidus pedicle", which is a modification of the superomedial pedicle, for managing large breast cancers (BCs) in the upper outer quadrant (UOQ) in patients with medium/large breasts and associated ptosis. Observed complications, cosmetic outcome and oncologic safety were also reported. MATERIALS AND METHODS: Thirty patients underwent our modification of the superomedial pedicle combined with a Wise skin resection pattern for large BCs in the UOQ. All patients underwent contralateral Wise pattern breast reduction/mastopexy for symmetry. RESULTS: The average weight of the quadrantectomy specimen was 235 grams (range: 36-400 grams). Mean free tumour margin was 19.4 mm (range: 16-30). Mean operative time was 165 minutes (range: 150-220). Eight (13.2%) breasts had minor complications: two partial NAC necrosis, and six minimal wound dehiscences. Mean follow-up was 22 months (range: 12-30). Overall satisfaction rate was 91%; patients reported to be satisfied the most with the shape (92%) of the breasts, the achieved symmetry (94%), and the volume (85%), focusing on the fullness in the UOQ. CONCLUSIONS: Our Bifidus pedicle allowed to fill even wide defects in the UOQ, because we selectively employed it in patients with medium to large ptotic breasts where the lower pole had enough tissue to be displaced. Satisfactory cosmetic and oncologic outcomes were achieved with low complication rate. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Silymarin in Combination with Vitamin C, Vitamin E, Coenzyme Q10 and Selenomethionine to Improve Liver Enzymes and Blood Lipid Profile in NAFLD Patients.

Background and Objectives: Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging cause of hepatopathy that is showing an increasing trend and where the recommendations of lifestyle modification are often not sufficient. The aim of this study is to evaluate the efficacy and tolerability profile of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) by analyzing liver enzymes, along with the lipidic profile, as markers of liver function, and ultrasound results in NAFLD patients. Materials and Methods: This study enrolled 81 patients with mild to severe NAFLD, divided into two groups: Group A (N = 41) received two capsules a day of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®), and Group B (N = 40) received only recommendations for lifestyle modification including hypocaloric diet, physical exercise and encouragement for weight loss. Patients have been evaluated at three timepoints: baseline (T0), after 45 days of treatment (T1) and after 90 days of treatment (T2), by collecting blood parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and the lipid blood profile. Ultrasonographic results have been analyzed at T0 and T2, along with the tolerability profile and side effects, registered at time T2. Results: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective since it showed a significant reduction of the evaluated parameters of ALT, AST, ALP and GGT, a significant improvement of lipid parameters, evaluated as markers of liver function, and improvements of ultrasonographic results. The use of this formulation at the dosage of two capsules a day has been well tolerated and no adverse events have been reported during study period of three months. Conclusions: The administration of the association of silymarin, vitamin C, vitamin E, coenzyme Q10 and selenomethionine (Medronys epato®) was effective and well tolerated in the improvement of hepatic function of NAFLD patients.