HER2 mutation as an emerging target in advanced breast cancer.

HER2 activating mutations have emerged as oncogenic drivers and therapeutic targets in a variety of human tumors. In breast cancer, these deregulations occur at low frequency, and are mostly detected in HER2-nonamplified, metastatic disease. Preclinical evidence has clarified the role of hotspot mutations in HER2 constitutive activation, defining them as an alternative mechanism to HER2 gene amplification. Furthermore, recent clinical studies have indicated the emergence of newly acquired HER2 deregulations in significant proportions of breast cancer patients who experience disease progression following both endocrine and HER2-targeted therapies. As the involvement of HER2 mutation in therapy resistance may profoundly impact patient outcomes on successive therapies, several clinical trials are currently investigating the efficacy of various HER2-targeted drugs in HER2-mutant breast cancer. In this review, we firstly summarize the structural organization of the HER2 oncogene and its historical impact on breast cancer prognosis and therapeutic advancement. Then, we provide an overview of the frequencies and functional relevance of clinically recurrent HER2 mutations in breast cancer with a special focus on their role in therapeutic resistance. Finally, we provide a collection of the clinical trials that are currently exploring novel therapeutic approaches for this patient subset and discuss the related perspectives and challenges.

Surgical site infections in patients undergoing breast oncological surgery during the lockdown: An unexpected lesson from the COVID-19 pandemic.

Background: The present study aims to evaluate how the measures to contain the SARS-CoV-2 spreading affected the surgical site infections (SSIs) rate in patients who underwent nondeferrable breast cancer surgery (BCS). Methods: This study is a retrospective analysis of prospectively collected data from a consecutive series of patients underwent nondeferrable BCS in a regional Italian Covid-free hub during two different period: March to April 2020 (pandemic cohort [PC]) and March till April 2019 (control cohort [CC]). SSIs were defined according to the criteria established by the Center for disease control and prevention (CDC) and additional treatment, serous discharge, erythema, purulent exudate, separation of deep tissues, isolation of bacteria, and stay (ASEPSIS) scoring systems. Results: One hundred ninety-nine patients were included in the present study: 100 and 99 patients who underwent nondeferrable BCS from March to April 2020 (PC) and from March to April 2019 (CC), respectively. The overall SSIs rate in this series was 9.1% according to CDC criteria and 6.5% according to ASEPSIS criteria. The SSIs incidence decreased during the pandemic period. Moreover, the SSIs rate according to ASEPSIS criteria was statistically lower in the PC than in the CC. We observed significant evidence of higher SSIs, both in terms of CDC and ASEPSIS score, in patients having undergone breast reconstruction compared with patients not undergoing immediate reconstruction. Conclusions: The restrictive measures issued during the lockdown period seemed to lower the SSIs rates in patients undergoing nondeferrable BCS.

Combined approach with negative pressure wound therapy and biological mesh for treatment of enterocutaneous fistula after synthetic mesh repair of incisional hernia. A case report.

AIM: Enterocutaneous fistula is a rare but severe complication of prosthetic incisional hernia repair. Management requires re-exploration with intestinal repair/resection and mesh removal. Repair of the parietal defect in this contaminated field is challenging. MATERIAL OF STUDY: A 58-years male patient presented to our department one year after synthetic mesh repair of large incisional hernia with mesh infection and enterocutaneous fistula. The diagnosis was confirmed by ultrasound guided drainage and CT scans with oral contrast. A multiple-step surgical approach has been adopted: first, the mesh was removed, intestinal resection performed and posterior fascial closure obtained by bilateral transversus abdominis release (TAR) and supra-fascial NPWT (negative pressure wound therapy) was positioned and maintained for one week; second, a definitive repair was obtained by a biological prothesis fixed to posterior fascia and covered by anterior fascia closure. Then, new NPWT was positioned and maintained for 6 days on the skin closure. At 18-months follow-up, the patient showed no clinical or radiological signs of recurrence or reinfection. DISCUSSION: Surgical strategies to face enterocutaneous fistula after prosthesis ventral hernia repair are not standardized. After bowel fistula treatment and mesh removal, the challenge of abdominal wall closure stay unsolved because of the high rate of complication and failure of a new prosthetic repair. A case-by-case management plan, often with the use of a multi-step strategy, may be an option. CONCLUSION: This is a single recovery multiple-step strategy combined approach using NPWT and biological prothesis to manage a case of mesh infection by an enterocutaneous fistula. This unique approach has revealed safe and effective for the treatment of parietal defect in infected field resulting from a mesh removing procedure. KEY WORDS: Biological prosthesis, Bowel mesh erosion, Enterocutaneous fistula, Negative Pressure Wound Therapy, Open incisional hernia repair.

Complications of postlaparoscopic sleeve gastric resection: review of surgical technique.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a very frequent procedure in bariatric surgery. Despite its simplicity, it can have serious complications. Among these, gastric leak is one of the most feared complications. Numerous intraoperative maneuvers have been suggested in an attempt to decrease the incidence of leak. In our center, we decided to study one of the intraoperative measures proposed, which consists in positioning the suture machine to 1.5 cm from His corner. METHODS: This retrospective study reported 101 cases of LSG performed in our center from 2012 to 2017. The patients were divided into two groups, with comparable anthropometric parameters and comparable inclusion criteria. In the two groups the operative technique used was the same, except for a maneuver: in the second group, attention was paid to keep a distance from the angle of at least 1.5 cm. RESULTS: On a total of 101 procedures performed, the overall complication rate was 4,95%. In group 1 the rate of gastric staple line leak was 6.78%. In group 2 the rate was 2.38%. CONCLUSIONS: The analyzed surgical technique seems to decrease the risk of leak without significantly impacting weight loss, and we have noticed in our clinical experience a decrease in the incidence of fistula from the time this measure was adopted. Also the statistical analysis encourage the continuation of experimentation.