Breast tissue imaging atlas using ultra-fast confocal microscopy to identify cancer lesions.

New generation ultra-fast fluorescence confocal microscopy (UFCM) allows to image histological architecture of fresh breast tissue and may be used for ex vivo intraoperative analysis for margin status. The criteria to identify breast tumoral and non-tumoral tissues in UFCM images are still objects of investigation. The objective of the study was to create an atlas of ex vivo UFCM images of breast tissues and breast carcinomas based on the first extensive collection of large field-of-view UFCM breast images. One hundred sixty patients who underwent conserving surgery for breast cancer were included. Their fresh surgical specimens were sliced, stained with acridine orange, and imaged at high resolution with large-field-of-view UFCM. The resulting images were digitally false colored to resemble frozen sections. Each UFCM image was correlated with the corresponding definitive histology. Representative images of normal tissue, inflammation, benign lesions, invasive carcinoma (IC), and ductal carcinoma in situ (DCIS) were collected. A total of 320 large-field images were recorded from 58 IC of no special type, 44 invasive lobular carcinomas, 1 invasive mucinous carcinoma, 47 DCIS, 2 lobular carcinomas in situ, and 8 specimens without cancer. Representative images of the main components of the normal breast and the main types of ICs and DCIS were annotated to establish an UFCM atlas. UFCM enables the imaging of the fresh breast tissue sections. Main morphological criteria defined in traditional histopathology such as tissue architecture and cell features can be applied to describe UFCM images content. The generated atlas of the main normal or tumoral tissue features will support the adoption of this optical technology for the intraoperative examination of breast specimens in clinical practice as it can be used to train physicians on UFCM images and develop artificial intelligence algorithms. Further studies are needed to document rare breast lesions.

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).

Facing points of view: Representations on adjuvant endocrine therapy of premenopausal patients after breast cancer and their healthcare providers in France. The FOR-AD study.

PURPOSE: Adjuvant endocrine therapy (ET) for 5-10 years is the backbone of the therapeutic strategy in patients with hormone receptor positive (HR+) early breast cancer (BC). However, long-term adherence to adjuvant ET represents a major challenge for most patients. According to prior studies, side effects of adjuvant ET are an important reason for poor adherence. In contrast, better communication and relational bond between patients and healthcare providers (HCPs) may improve adherence. The FOR-AD (Focus on non-adherence) study aimed at better understanding the representation of adjuvant ET by patients and their HCPs, in order to improve the care process. METHODS: Three focus groups of premenopausal women (receiving adjuvant ET for variable amount of time) and two focus groups of HCPs (including oncologists, pharmacists, and nurses) were conducted, each including around ten participants. Thematic analyses using a general inductive approach were constructed to report participants' representations. RESULTS: Two main themes emerged across groups, and appeared of major importance. Representations on adjuvant ET were often homogenous within each group, but differed between patients and their HCPs. The relationship between both groups was considerably discussed, particularly its importance in facilitating adherence to adjuvant ET. Suggestions on improving the care process were also given, such as systematically including psychologists in follow-up care paths and having a nurse navigator follow patients under treatment with adjuvant ET. CONCLUSION: The present qualitative exploration may help buildi future tailored interventions to improve adherence to adjuvant ET, in particular regarding the role of nurse navigators.

Axillary reverse mapping using near-infrared fluorescence imaging in invasive breast cancer (ARMONIC study).

BACKGROUND: Axillary lymph node dissection (ALND) in patients with breast cancer has potential side effects, including upper-limb lymphedema. Axillary reverse mapping (ARM) is a technique that enables discrimination of the lymphatic drainage of the upper limb in the axillary lymph node basin from that of the breast. We aimed to evaluate ARM node identification by near-infrared (NIR) fluorescence imaging during total mastectomy with ALND and then to analyze potential predictive factors of ARM node involvement. METHODS: The study enrolled 119 patients diagnosed with invasive breast cancer with an indication for ALND. NIR imaging using indocyanine green dye was performed in 109 patients during standard ALND to identify ARM nodes and their corresponding lymphatic ducts. RESULTS: 94.5% of patients had ARM nodes identified (95%CI = [88.4-98.0]). The ARM nodes were localized in zone D in 63.4% of cases. Metastatic axillary lymph nodes were found in 55% in the whole cohort, and 19.4% also had metastasis in ARM nodes. Two patients had metastatic ARM nodes but not in the remaining axillary lymph nodes. No serious adverse events were observed. Only the amount of mitosis was significantly associated with ARM node metastasis. CONCLUSIONS: ARM by NIR fluorescence imaging could be a reliable technique to identify ARM nodes in real-time when ALND is performed. The clinical data compared with ARM node histological diagnosis showed only the amount of mitosis in the diagnostic biopsy is a potential predictive factor of ARM node involvement. CLINICAL TRIAL REGISTRATION: NCT02994225.

Near-Infrared Fluorescence Axillary Reverse Mapping (ARM) Procedure in Invasive Breast Cancer: Relationship between Fluorescence Signal in ARM Lymph Nodes and Clinical Outcomes.

The near-infrared (NIR) fluorescence axillary reverse mapping (ARM) procedure is a promising tool to identify and preserve arm lymphatic drainage during axillary lymph node dissection (ALND). The ARMONIC clinical trial was conducted to validate the technique on a large cohort of patients and to analyze the predictive clinical factors for ARM lymph node metastasis. For the first time, the fluorescence signal intensity from the ARM lymph nodes was measured and correlated with clinical findings. A total of 109 patients with invasive breast cancer and indications of mastectomy and ALND underwent the NIR fluorescence ARM procedure. Indocyanine green was administered by intradermal injection followed by intraoperative identification and resection of the ARM lymph nodes with NIR fluorescence camera guidance. The fluorescence signal intensity and signal distribution were then measured ex vivo and compared with clinical outcomes. ARM lymph nodes were successfully identified by fluorescence in 94.5% of cases. The mean normalized fluorescence signal intensity value was 0.47 with no significant signal difference between metastatic and non-metastatic ARM lymph nodes (p = 0.3728). At the microscopic level, the fluorescence signal distribution was focally intense in lymphoid tissue areas. Only the preoperative diagnosis of metastasis in the axillary nodes of patients was significantly associated with a higher ARM node fluorescence signal intensity (p = 0.0253), though it was not significantly associated with the pathological nodal (pN) status (p = 0.8081). Based on an optimal cut-off fluorescence value, the final sensitivity and specificity of the NIR fluorescence ARM procedure for ARM lymph node metastatic involvement were 64.7% and 47.3%, respectively. Although our preliminary results did not show that fluorescence signal intensity is a reliable diagnostic tool, the NIR fluorescence ARM procedure may be useful for ARM lymph node identification. Clinical trial registration: NCT02994225.

Near-infrared fluorescence imaging for the prevention and management of breast cancer-related lymphedema: A systematic review.

Sentinel lymph node identification by near infrared (NIR) fluorescence with indocyanine green (ICG) is recognized in the literature as a useful technique. NIR fluorescence technology could become key in the prevention and management of lymphedema after axillary dissection for breast cancer. Here, we conducted a systematic review focusing on ICG imaging to improve lymphedema prevention and treatment after axillary surgery. A systematic literature review was performed using MEDLINE and Embase to identify articles focused on ICG imaging for breast-cancer-related lymphedema (BCRL). Qualitative analysis was performed to summarize the characteristics of reported ICG procedures. In situ tissue identification and functionality assessment based on fluorescence signal were evaluated. Clinical outcomes were appraised when reported. Studies relating to axillary reverse mapping, lymphography and upper limb supermicrosurgery combined with ICG imaging were identified. We included a total of 33 relevant articles with a total of 2016 patients enrolled. ICG imaging for axillary reverse mapping was safe for all 951 included patients, with identification of arm nodes in 80%-88% of patients with axillary lymph nodes dissection. However, the papers discuss the oncologic safety of the approach and how - regardless of the contrast agent - concerns limit its adoption. ICG lymphography is openly supported in BCRL management, with 1065 patients undergoing this procedure in 26 articles. The technique is reported for lymphedema diagnosis, with high sensitivity and specificity, staging, intraoperative mapping and patency control in lymphaticovenular anastomosis. The substantial advantages/disadvantages of ICG imaging procedures are finally described.

Prospective evaluation of the limitations of near-infrared imaging in detecting axillary sentinel lymph nodes in primary breast cancer.

We compared the performance of near-infrared imaging using indocyanine green (ICG) with the radioisotope (ISO) method to detect sentinel lymph nodes (SLNs) in breast cancer, to analyze predictive factors for negative ICG identification. The study included 122 patients who underwent sentinel lymph node biopsy (SLNB) using the combined ISO and ICG technique for primary breast cancer. We assessed the putative association between pathologic/clinical variables and ICG failure to detect SLNs. The ISO identification rate was 96.7% and ICG identification 81.9%. Overweight patients or presence of macrometastasis in SLNB were associated with the risk of ICG failing to detect SLNs (P = 0.02).

Robotic Prophylactic Nipple-Sparing Mastectomy with Immediate Prosthetic Breast Reconstruction: A Prospective Study.

BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) could be a significant advancement in the treatment of breast cancers and prophylaxis because the mastectomy is performed without leaving any scar on the breast. The aim of this study was to assess the feasibility and the safety of RNSM with immediate prosthetic breast reconstruction (IPBR). METHODS: In this prospective study, RNSM with IPBR was offered to patients with breast cup size A, B or C and ptosis grade ≤ 2. In case of oncologic surgery, RNSM was proposed only if the tumor was located more than 2 cm away from the nipple-areola complex (NAC) and if postoperative radiation was not indicated. In case of prophylactic surgery, RNSM was proposed only if a high-risk genetic mutation had been identified. The primary endpoint was the rate of skin or NAC necrosis. The rate of conversion to open technique, the duration of the procedure, and postoperative complications were also analyzed. RESULTS: Sixty-three RNSM with IPBR were performed in 33 patients. There were no cases of mastectomy skin flap or NAC necrosis. We had to convert to an open technique in one case (1.6%). Three infections occurred (4.8%), one leading to implant loss (1.6%). No other major complications were observed. CONCLUSIONS: Preliminary data attest to the feasibility, the reproducibility, and the safety of this approach. However, long-term data are needed to confirm the oncological safety and the esthetic stability of the result. Trial registration identifier NCT02673268.

Use of Low-Thrombin Fibrin Sealant Glue After Axillary Lymphadenectomy for Breast Cancer to Reduce Hospital Length and Seroma.

BACKGROUND: Axillary lymphadenectomy for primary breast cancer produces a non-negligible rate of postoperative lymphorrhea, prolonged hospital stays, and multiple seroma punctures. We evaluated the impact of low-thrombin fibrin sealant glue on surgical wounds in patients undergoing axillary lymph node dissection for breast cancer. METHODS: We conducted an observational study of 149 patients who underwent axillary lymphadenectomy for primary breast cancer between January 2014 and December 2015. Data were obtained from 2 successive prospective studies. The hospital stay length and morbidity (seromas, punctures) were compared between 2 groups: patients who had padding sutures and low-thrombin fibrin sealant glue without drainage (n = 49) and patients with drainage alone (n = 100). Hospital costs were assessed from the hospital perspective. RESULTS: The mean hospital stay length was shorter in the fibrin sealant group (2.6 vs. 4.7 days; P < .001). Seroma magnitude and punctures were similar in patients treated with fibrin sealant compared with patients with drainage alone. The rate of needle aspiration for seroma was similar irrespective of whether or not a drain or fibrin sealant was used (30.6% vs. 33.0%, P = .77). CONCLUSION: Low-thrombin fibrin sealant glue does not significantly reduce the amount of fluid produced in the axilla after breast surgery; however, its systematic use may help reduce hospital stays and costs.

Gastrointestinal bleeding as presentation of small bowel metastases of malignant melanoma: Is surgery a good choice?

INTRODUCTION: Melanoma shows a particular predilection in involving small intestine both in a single site and in multiple localization and acute or chronic gastrointestinal bleedings are often the first sign of tumour. PRESENTATION OF CASE: We report two cases of GI metastases of malignant melanoma, one presented with only a big mass that cause intestinal obstruction and the other with a tumour spread throughout the small intestine that produce enterorrhagia. DISCUSSION: Diagnosis and follow-up are very difficult: CT scan, PET-CT scan and capsule endoscopy should be complementary for the assessment of patients with GI symptoms and melanoma history. CONCLUSION: What is the role of surgery? Several studies suggest metastasectomy to achieve both R0 results and palliative resolutions of acute symptoms, such as obstruction, pain, and bleeding.

Idiopathic adult colo-colonic intussusception: Case report and review of the literature.

INTRODUCTION: Acute colonic intussusception occurring in the absence of organic cause is uncommon in adults. PRESENTATION OF CASE: We report acute colonic intussusception in a 46-year-old female; clinical evidence of a palpable mass, abdominal pain and bloody mucoid stools appeared a few hours after hospital admission. Multislice CT-scan confirmed the clinical diagnosis and surgical exploration revealed right colonic obstruction caused by intussusception of the cecum into the ascending colon. Right hemicolectomy was performed and histopathological examination did not reveal any causative pathology. DISCUSSION: Intussusception remains a rare condition in adults, representing 1-5% of bowel obstruction and accounting for 0.003-0.02% of all hospital admissions. Intussusception occurs more frequently in the small (50-80%) than in the large bowel (12-50%). It is estimated that approximately 90% of intussusceptions in adults are secondary to an anatomical or pathological condition, of which more than half are malignant. Idiopathic cases are the exception in adults. The clinical presentation of adult intussusception differs considerably from the classic pediatric presentation of abdominal pain, palpable mass, and blood per rectum, which is rarely seen in adults. A pre-operative CT-scan showed a 10cm intussuscepted segment of right colon. Surgical resection was considered mandatory because of severe bowel obstruction, and the theoretical possibility of occult malignancy. This approach was vindicated by the presence of widespread ischemic lesions in the wall of the resected bowel, without any obvious lead point. CONCLUSION: There are few reports in the medical literature of acute colonic intussusception occurring in the absence of organic cause in adults.

Splenic localization of the peritoneal mesothelioma: case report and literature revue.

Peritoneal mesothelioma is a rare form of malignant mesothelioma, making up <30% of diagnosed mesothelioma cases. Because of a lack of specific symptoms (abdominal pain, abdominal swelling), normally it is diagnosed in advanced stages, sometimes in a surgical emergency (intestinal obstruction, severe ascites) and occasionally during image procedures or laparoscopy which can show a mass developing from peritoneal mesothelium surfaces, or an accumulation of small irregularities that may be tumors or plaques. The reported case refers to a particular localization of a peritoneal mesothelioma, the spleen, discovered only after a splenectomy, due to the clinical and radiological suspect of a rupture.