Breast carcinoma detection in ex vivo fresh human breast surgical specimens using a fast slide-free confocal microscopy scanner: HIBISCUSS project.

BACKGROUND: New generation ultra-fast fluorescence confocal microscopy allows the ex vivo intraoperative analysis of fresh tissue. The High resolution Imaging for Breast carcInoma detection in ex vivo Specimens after breast Conserving sUrgery by hiStolog Scanner (HIBISCUSS) project aimed to develop an online learning program to recognize the main breast tissue features on ultra-fast fluorescence confocal microscopy images and to evaluate the performance of surgeons and pathologists in diagnosing cancerous and non-cancerous breast tissue in ultra-fast fluorescence confocal microscopy images. METHODS: Patients who underwent conservative surgery or mastectomy for breast carcinoma (invasive or in situ lesions) were included. The fresh specimens were stained with a fluorescent dye and imaged using a large field-of-view (20 cm2) ultra-fast fluorescence confocal microscope. RESULTS: One hundred and eighty-one patients were included. The images from 55 patients were annotated to generate learning sheets and images from 126 patients were blindly interpreted by seven surgeons and two pathologists. The time for tissue processing and ultra-fast fluorescence confocal microscopy imaging was between 8 and 10 min. The training program was composed of 110 images divided into nine learning sessions. The final database for blind performance assessment comprised 300 images. The mean duration for one training session and one performance round was 17 and 27 min respectively. The performance of pathologists was almost perfect with 99.6 per cent (standard deviation (s.d.) 5.4 per cent) accuracy. Surgeons' accuracy significantly increased (P = 0.001) from 83 per cent (s.d. 8.4 per cent) in round 1 to 98 per cent (s.d. 4.1 per cent) in round 7 as well as the sensitivity (P = 0.004). Specificity increased without significance from 84 per cent (s.d. 16.7 per cent) in round 1 to 87 per cent (s.d. 16.4 per cent) in round 7 (P = 0.060). CONCLUSION: Pathologists and surgeons showed a short learning curve in differentiating breast cancer from non-cancerous tissue in ultra-fast fluorescence confocal microscopy images. Performance assessment for both specialties supports ultra-fast fluorescence confocal microscopy evaluation for intraoperative management. REGISTRATION NUMBER: NCT04976556 (http://www.clinicaltrials.gov).

A Pure Autologous Dermal Graft and Dermal Flap Pocket in Prepectoral Implant Reconstruction After Skin-Reducing Mastectomy: A One-Stage Autologous Reconstruction Alternative to Acellular Dermal Matrices.

Skin-reducing mastectomy (SRM) with subpectoral implant positioning represents a consolidated, oncologically safe and cosmetically effective method for the immediate reconstruction of large and ptotic breasts. Acellular dermal matrix (ADM) has been proposed as a substitute for the pectoralis major muscle in this surgical approach; this technique led to a progressive evolution toward prepectoral reconstructions even in skin-reducing mastectomies. Obese patients with macromastia who are typical candidates for SRM with ADM are at increased risk of complications associated with ADMs. Therefore, we avoided ADMs and developed a novel autologous technique for immediate breast reconstruction in large and ptotic breasts eligible for SRM. Specifically, an autologous dermal graft is harvested from contralateral healthy breast reduction to cover the upper pole of the prepectoral implant.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 .

Biomarkers Changes after Neoadjuvant Chemotherapy in Breast Cancer: A Seven-Year Single Institution Experience.

The adoption of neoadjuvant chemotherapy (NACT) for breast cancer (BC) is increasing. The need to repeat the biomarkers on a residual tumor after NACT is still a matter of debate. We verified estrogen receptors (ER), progesterone receptors (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) status changes impact in a retrospective monocentric series of 265 BCs undergoing NACT. All biomarkers changed with an overall tendency toward a reduced expression. Changes in PR and Ki67 were statistically significant (p = 0.001). Ki67 changed in 114/265 (43.0%) cases, PR in 44/265 (16.6%), ER in 31/265 (11.7%) and HER2 in 26/265 (9.8%). Overall, intrinsic subtype changed in 72/265 (27.2%) cases after NACT, and 10/265 (3.8%) cases switched to a different adjuvant therapy accordingly. Luminal subtypes changed most frequently (66/175; 31.7%) but with less impact on therapy (5/175; 2.8%). Only 3 of 58 triple-negative BCs (5.2%) changed their intrinsic subtype, but all of them switched treatment. No correlation was found between intrinsic subtype changes and clinicopathological features. To conclude, biomarkers changes with prognostic implications occurred in all BC intrinsic subtypes, albeit they impacted therapy mostly in HER2 negative and/or hormone receptors negative BCs. Biomarkers retesting after NACT is important to improve both tailored adjuvant therapies and prognostication of patients.

Reduced graphene oxide on silicon-based structure as novel broadband photodetector.

Heterojunction photodetector based on reduced graphene oxide (rGO) has been realized using a spin coating technique. The electrical and optical characterization of bare GO and thermally reduced GO thin films deposited on glass substrate has been carried out. Ultraviolet-visible-infrared transmittance measurements of the GO and rGO thin films revealed broad absorption range, while the absorbance analysis evaluates rGO band gap of about 2.8 eV. The effect of GO reduction process on the photoresponse capability is reported. The current-voltage characteristics and the responsivity of rGO/n-Si based device have been investigated using laser diode wavelengths from UV up to IR spectral range. An energy band diagram of the heterojunction has been proposed to explain the current versus voltage characteristics. The device demonstrates a photoresponse at a broad spectral range with a maximum responsivity and detectivity of 0.20 A/W and 7 × 1010 cmHz/W, respectively. Notably, the obtained results indicate that the rGO based device can be useful for broadband radiation detection compatible with silicon device technology.

Accuracy and Reproducibility of Contrast-Enhanced Mammography in the Assessment of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients with Calcifications in the Tumor Bed.

This study aimed to evaluate contrast-enhanced mammography (CEM) accuracy and reproducibility in the detection and measurement of residual tumor after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with calcifications, using surgical specimen pathology as the reference. Pre- and post-NAC CEM images of 36 consecutive BC patients receiving NAC in 2012-2020, with calcifications in the tumor bed at diagnosis, were retrospectively reviewed by two radiologists; described were absence/presence and size of residual disease based on contrast enhancement (CE) only and CE plus calcifications. Twenty-eight patients (77.8%) had invasive and 5 (13.9%) in situ-only residual disease at surgical specimen pathology. Considering CE plus calcifications instead of CE only, CEM sensitivity for invasive residual tumor increased from 85.7% (95% CI = 67.3-96%) to 96.4% (95% CI = 81.7-99.9%) and specificity decreased from 5/8 (62.5%; 95% CI = 24.5-91.5%) to 1/8 (14.3%; 95% CI = 0.4-57.9%). For in situ-only residual disease, false negatives decreased from 3 to 0 and false positives increased from 1 to 2. CEM pathology concordance in residual disease measurement increased (R squared from 0.38 to 0.45); inter-reader concordance decreased (R squared from 0.79 to 0.66). Considering CE plus calcifications to evaluate NAC response in BC patients increases sensitivity in detection and accuracy in measurement of residual disease but increases false positives.

MRI in Pregnancy and Precision Medicine: A Review from Literature.

Magnetic resonance imaging (MRI) offers excellent spatial and contrast resolution for evaluating a wide variety of pathologies, without exposing patients to ionizing radiations. Additionally, MRI offers reproducible diagnostic imaging results that are not operator-dependent, a major advantage over ultrasound. MRI is commonly used in pregnant women to evaluate, most frequently, acute abdominal and pelvic pain or placental abnormalities, as well as neurological or fetal abnormalities, infections, or neoplasms. However, to date, our knowledge about MRI safety during pregnancy, especially about the administration of gadolinium-based contrast agents, which are able to cross the placental barrier, is still limited, raising concerns about possible negative effects on both the mother and the health of the fetus. Contrast agents that are unable to cross the placenta in a way that is safe for the fetus are desirable. In recent years, some preclinical studies, carried out in rodent models, have evaluated the role of long circulating liposomal nanoparticle-based blood-pool gadolinium contrast agents that do not penetrate the placental barrier due to their size and therefore do not expose the fetus to the contrast agent during pregnancy, preserving it from any hypothetical risks. Hence, we performed a literature review focusing on contrast and non-contrast MRI use during pregnancy.

Comorbidities, Cardiovascular Therapies, and COVID-19 Mortality: A Nationwide, Italian Observational Study (ItaliCO).

Background: Italy has one of the world's oldest populations, and suffered one the highest death tolls from Coronavirus disease 2019 (COVID-19) worldwide. Older people with cardiovascular diseases (CVDs), and in particular hypertension, are at higher risk of hospitalization and death for COVID-19. Whether hypertension medications may increase the risk for death in older COVID 19 inpatients at the highest risk for the disease is currently unknown. Methods: Data from 5,625 COVID-19 inpatients were manually extracted from medical charts from 61 hospitals across Italy. From the initial 5,625 patients, 3,179 were included in the study as they were either discharged or deceased at the time of the data analysis. Primary outcome was inpatient death or recovery. Mixed effects logistic regression models were adjusted for sex, age, and number of comorbidities, with a random effect for site. Results: A large proportion of participating inpatients were ≥65 years old (58%), male (68%), non-smokers (93%) with comorbidities (66%). Each additional comorbidity increased the risk of death by 35% [adjOR = 1.35 (1.2, 1.5) p < 0.001]. Use of ACE inhibitors, ARBs, beta-blockers or Ca-antagonists was not associated with significantly increased risk of death. There was a marginal negative association between ARB use and death, and a marginal positive association between diuretic use and death. Conclusions: This Italian nationwide observational study of COVID-19 inpatients, the majority of which ≥65 years old, indicates that there is a linear direct relationship between the number of comorbidities and the risk of death. Among CVDs, hypertension and pre-existing cardiomyopathy were significantly associated with risk of death. The use of hypertension medications reported to be safe in younger cohorts, do not contribute significantly to increased COVID-19 related deaths in an older population that suffered one of the highest death tolls worldwide.

Bifurcate inferior pedicle mammoplasty in large ptotic breast for tumor located at the upper outer quadrant with skin involvement-a novel technique allowing good cosmetic outcome: case report.

Breast oncoplastic techniques followed by radiotherapy represent nowadays the standard of care for breast cancer treatment. For tumours located at the upper outer quadrant in patients with large and ptotic breasts, the use of level II breast reduction mammoplasty, allows large quadrantectomies without compromising the breast natural shape and reducing the breast volume to be irradiated. When the skin overlying the tumour in the upper outer quadrant is involved, the removal of the skin during mammoplasty could lead to an extreme reduction of the breast, resulting in a bad outcome. Different strategies have been adopted to avoid a poor cosmetic result including a Z plastic or latissimus dorsi (LD) mini flap. At our institution we developed a new technique utilizing an inferior bifurcated pedicle mammoplasty with the preservation of a skin island for a patient with a residual tumour following chemotherapy involving the skin in the upper outer quadrant of the right breast. The patient did show no complications, with no delay for adjuvant radiotherapy treatment. Our method is a novel technique to treat malignancies in this location for patients with large and ptotic breasts when skin removal is indicated and it may represent an effective strategy to prevent excessive gland reduction, thus avoiding poor cosmetic result.

The Bovine Pericardium Matrix in Immediate Implant-Based Breast Reconstruction.

BACKGROUND: Acellular dermal matrices have been introduced to optimize direct-to-implant breast reconstruction. We selected a bovine pericardium noncross-linked matrix. METHODS: The study consists in the retrospective analysis of 123 patients (141 breasts) who underwent conservative mastectomy and immediate implant-based breast reconstruction with bovine pericardium matrix Veritas® from March 2012 to October 2017. RESULTS: The overall rates of early and late complications, after a median follow-up of 51.84 months, were, respectively, 37.6% and 24.1%. The most noticeable early complications were flap ischemia [n = 39 (27.7%)], hematoma [n = 5 (3.6%)], marginal skin flap necrosis [n = 5 (3.6%)] and dehiscence of the surgical wound [n = 2 (1.4%)]. The most common late complications were rippling [n = 18 (12.7%)] and seroma [n = 4 (2.8%)]. The rate of clinically relevant capsular contracture was low: 12.1% (n = 17) presented grade II and only 2.1%% (n = 3) grade III. Implant substitution became necessary for five patients (3.6%). Early complications occurred more frequently in patients undergoing therapeutic mastectomy (p = 0.031). Patients undergoing preoperative radiotherapy more frequently developed late complications (p = 0.012). A clinically relevant capsular contracture (grade II-III) was found in higher average patients age (p = 0.0019). The left side developed less frequently late complications except for rippling (p = 0.002). Rippling occurred more frequently in patients who sustained a nipple skin-sparing mastectomy (p = 0.035). CONCLUSION: Our results further support the safety of Veritas® in immediate implant-based breast reconstruction. 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 .

Bipedicled Nipple-Sparing Mastectomy Versus Traditional Nipple-Sparing Mastectomy: Comparison of 2 Alternative Techniques in Order to Save Nipple-Areola Complex.

BACKGROUND: Nipple-areola complex-sparing mastectomy (NSM) represents, when a mastectomy is unavoidable, the best treatment possible that can be offered to attenuate the negative impact of surgery on patients' quality of life. Unfortunately, NSM can be used only in selected patients with small and nonptotic breasts. In order to save the nipple-areola complex (NAC) also in patients with large and ptotic breast, otherwise subjected to a skin-sparing mastectomy with the sacrifice of the NAC, we described the bipedicled nipple-sparing mastectomy (BNSM). The aim of this study is to obtain a formal outcome assessment of BNSM and analyze the complications rate of this technique compared with traditional NSM. We furthermore attempt to describe the surgical procedures present in the literature that allow to preserve NAC also in large and ptotic breasts presenting the complication rates observed and comparing with our technique. Aesthetic outcome has also been evaluated. METHODS: We retrospectively reviewed 42 procedures of consecutive patients undergoing immediate reconstruction with tissue expanders after NSM (20 patients) or BNSM (19 patients). We divided them in 2 groups focused on surgical complications and aesthetic outcome. RESULTS: On a total of 42 procedures, the principal major complication was dehiscence of surgical wound procedures needing 1-day surgery revision occurring in 3 (14.3%) of the BNSM group and 1 (4.8%) of the NSM group, whereas as principal minor complication 4 partial NAC necrosis not requiring surgery in BNSM (19%) and 2 (9.5%) in NSM. No tissue expanders required explantation. Concerning cosmetic results, the overall appearance of the breast and NAC was acceptable in 85.7 % and 77.2%, respectively, in the NSM group and 80.7% and 66.7%, respectively, in the BNSM group. CONCLUSIONS: Bipedicled nipple-sparing mastectomy is a valid technique to improve patients' quality of life in large and ptotic breasts otherwise candidate to a skin-sparing mastectomy, but only a progressive learning curve can minimize complications. No significant statistical differences have been observed in terms of complication rates and aesthetical outcomes between the 2 groups. An accurate selection of patients is mandatory in order to obtain low complication rates and good aesthetical outcome.

The axillary flap in oncoplastic resection of breast cancers located in the upper-outer quadrants: a new surgical technique.

BACKGROUND: The combination of breast conserving surgery (BCS) with plastic surgery techniques has provided a useful surgical tool matching the radicality of the oncological excision with the preservation of breast cosmesis. Even though BCS represents a good option for surgical treatment of tumors located in these quadrants, wide excisions often necessitate breast reshaping in order to avoid nipple areola complex (NAC) displacement and skin retraction. We present a new surgical technique to repair upper-outer quadrants' defects following breast cancer excision using dermo-glandular flaps and an axillary adipo-fascial flap. METHODS: During the period from January 2014 to December 2015, 168 patients with an upper-outer quadrant's breast cancer have been treated in our Department. 83 women have been treated with the described oncoplastic technique and immediate contra-lateral symmetrisation and 85 women underwent standard BCS. We present surgical, oncological and cosmetic outcomes comparing our results with standard BCS. RESULTS: At a mean follow-up of 27 months loco-regional recurrences in the two groups were comparable. Short-term complication rates were comparable between the two groups. Re-intervention rates for positive margins were significantly higher in the standard BCS group. The overall satisfaction with cosmetic outcome both assessed by the patient and the surgeon was significantly higher in the oncoplastic group. CONCLUSIONS: The proposed oncoplastic technique represents a safe and effective solution for reshaping that follows upper-outer breast cancer wide excision, achieving comparable complication rates, lower re-intervention rates for positive margins and better cosmetic results when compared with standard BCS.

Colonic metastasis from breast carcinoma detection by CESM and PET/CT: A case report.

INTRODUCTION: Metastatic spread in invasive lobular carcinoma (ILC) of breast mainly occurs in bones, gynecological organs, peritoneum, retroperitoneum, and gastrointestinal (GI) tract. Metastases to the GI tract may arise many years after initial diagnosis and can affect the tract from the tongue to the anus, stomach being the most commonly involved site. Clinical presentations are predominantly nonspecific, and rarely asymptomatic. CEA, CA 15-3, and CA 19-9 may be informative for symptomatic patients who have had a previous history of breast cancer. CASE PRESENTATION: We introduce the case of asymptomatic colonic metastasis from breast carcinoma in a 67-year-old woman followed-up for Luminal A ILC. Diagnosis was performed through positron emission tomography/computed tomography (PET/CT) scan and contrast-enhancement spectral mammography (CESM), steering endoscopist to spot the involved intestinal tract and in ruling out further dissemination in the breast parenchyma. CONCLUSION: In colonic metastases, tumor markers might not be totally reliable. In asymptomatic cases, clinical conditions might be underappreciated, missing local or distant recurrence. CT and PET/CT scan might be useful in diagnosing small volume diseases, and steering endoscopist toward GI metastasis originating from the breast. CESM represents a tolerable and feasible tool that rules out multicentricity and multifocality of breast localization. Moreover, particular patients could tolerate it better than magnetic resonance imaging (MRI).

Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.

BACKGROUND: Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. METHODS: This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin's coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). RESULTS: A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin's coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and 84%, respectively, for CESM, and 87% and 60% for MRI. CONCLUSION: CESM and MRI lesion size measurements were highly correlated. CESM seems at least as reliable as MRI in assessing the response to NAC, and may be an alternative if MRI is contraindicated or its availability is limited.

Applicability of the Proposed Japanese Model for the Classification of Gastric Cancer Location: The "PROTRADIST" Retrospective Study.

BACKGROUND: The extension of lymphadenectomy for surgical treatment of gastric cancer remains discordant among European and Japanese surgeons. Kinami et al. (Kinami S, Fujimura T, Ojima E, et al. PTD classification: proposal for a new classification of gastric cancer location based on physiological lymphatic flow. Int. J. Clin. Oncol. 2008;13:320-329) proposed a new experimental classification, the "Proximal zone, Transitional zone, Distal zone" (PTD) classification, based on the physiological lymphatic flow of gastric cancer site. The aim of the present retrospective study is to assess the applicability of PTD Japanese model in gastric cancer patients of our Western surgical department. METHODS: Two groups of patients with histologically documented adenocarcinoma of the stomach were retrospectively obtained: In the first group were categorized 89 patients with T1a-T1b tumor invasion; and in the second group were 157 patients with T2-T3 category. The data collected were then categorized according to the PTD classification. RESULTS: In the T1a-T1b group there were no lymph node metastases within the r-GA or r-GEA compartments for tumors located in the P portion, and similarly there were no lymphatic metastases within the l-GEA or p-GA compartments for tumors located in the D portion. On the contrary, in the T2-T3 group the lymph node metastases presented a diffused spreading with no statistical significance between the two classification models. CONCLUSIONS: Our results show that the PTD classification based on physiological lymphatic flow of the gastric cancer site is a more physiological and clinical version than the Upper, Medium And Lower classification. It represents a valuable and applicable model of cancer location that could be a guide to a tailored surgical approach in Italian patients with neoplasm confined to submucosa. Nevertheless, in order to confirm our findings, larger and prospective studies are needed.

Serratus Anterior Fascia Flap Versus Muscular Flap for Expander Coverage in Two-stage Breast Reconstruction Following Mastectomy: Early Post-operative Outcomes.

INTRODUCTION: The demand for reconstructive breast surgery after mastectomy is increasing among women and the two-stage option remains the most commonly performed technique. We conducted a self-controlled prospective clinical trial comparing the use of the serratus anterior fascia with the serratus anterior detached fibers to cover the inferolateral aspect of the expander in immediate two-stage breast reconstruction following conservative mastectomies as oncological or risk-reducing procedures. PATIENTS AND METHODS: We analyzed the surgical outcome of 29 bilateral mastectomies and immediate reconstruction with the positioning of a tissue expander in a pocket beneath the pectoralis major and serratus anterior muscle on one side and in a pocket beneath the pectoralis major and a serratus anterior fascia flap on the other side. We considered all complications presenting in the first month after surgery and patient-reported early post-operative pain. RESULTS: Complication rates in the two groups did not significantly differ (p = 0.237). The total amount of drainage and the time of drainage permanence were significantly lower for the subfascial group (p < 0.05). Patient-reported early post-operative pain was significantly different between the two groups both at 24 h (p < 0.05) and at 5 days (p < 0.05) with significantly lower pain scores reported by the patients in the subfascial group. DISCUSSION: Our self-controlled prospective trial demonstrated an advantage in performing an implant-based two-stage breast reconstruction using a serratus anterior fascia flap when compared with the serratus muscle fibers use for inferolateral implant coverage following mastectomy. The use of the anterior serratus fascia flap for inferolateral implant coverage in two-stage breast reconstructions following mastectomy could be considered as a safe and effective technique, presenting lower morbidity for the patient when compared with the serratus muscle fibers use and lower costs when compared with biological and synthetic meshes use, achieving good outcomes in terms of post-operative complications and women's quality of life and satisfaction levels. LEVEL OF EVIDENCE III: 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 .