Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride in Non-invasive Axillary Staging in Breast Cancer: Are we Missing a Chance?

BACKGROUND/AIM: In the context of surgical de-escalation in early breast cancer (EBC), this study aimed to evaluate the contrast enhancement ultrasound (CEUS) sentinel lymph node (SLN) procedure as a non-invasive axillary staging procedure in EBC in comparison with standard SLN biopsy (SLNB). PATIENTS AND METHODS: A subanalysis of the AX-CES study, a prospective single-arm, monocentric phase 3 study was performed (EudraCT: 2020-000393-20). The study included patients with EBC undergoing upfront surgery and SLN resection, with no prior history of locoregional treatment, and weighing between 40-85 kg. All patients underwent the CEUS SLN procedure as a non-invasive axillary staging procedure, with CEUS SLN accumulation marked using blue dye. After the CEUS SLN procedure, all patients underwent the standard mapping procedure. Data on success rate, systemic reactions, mean procedure time, mean surgical procedure, mean procedure without axillary staging, CEUS SLN appearance (normal/pathological), SLN number, and concordance with standard mapping procedure were collected. RESULTS: After the CEUS SLN procedure, 29 LNs among 16 patients were identified and marked. In all cases, CEUS SLN revealed at least one LN enhancement. Six (37.50%) LNs were defined as pathological after the CEUS SLN procedure. Definitive staining of CEUS SLN pathology revealed metastatic involvement in four (66.67%) of the cases. Two SLNs were identified during the CEUS SLN procedure; however, owing to the low disease burden, no change in the surgical plan was reported. CONCLUSION: The CEUS SLN procedure shows promise as a technique for non-invasive assessment of the axilla, potentially enabling safe axillary de-escalation in EBC by estimating the axillary disease burden.

Surgical De-Escalation for Re-Excision in Patients with a Margin Less Than 2 mm and a Diagnosis of DCIS.

The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging.

Cavity Shave Margins in Breast Conservative Surgery a Strategy to Reduce Positive Margins and Surgical Time.

Background: Resection of additional tissue circumferentially around the cavity left by lumpectomy (cavity shave) was suggested to reduce rates of positive margins and re-excision. Methods: A single center retrospective study which analyzed margins status, re-excision, and surgical time in patients who underwent breast conserving surgery and cavity shave or intraoperative evaluation of resection margins. Results: Between 2021 and 2023, 594 patients were enrolled in the study. In patients subjected to cavity shave, a significant reduction in positive, focally positive, or closer margins was reported 8.9% vs. 18.5% (p = 0.003). No difference was reported in terms of surgical re-excision (p < 0.846) (5% vs. 5.5%). Surgical time was lower in patients subjected to cavity shave (<0.001). The multivariate analysis intraoperative evaluation of sentinel lymph node OR 1.816 and cavity shave OR 2.909 were predictive factors for a shorter surgical time. Excluding patients subjected to intraoperative evaluation of sentinel lymph node and patients with ductal carcinoma in situ, patients that underwent the cavity shave presented a reduced surgical time (67.9 + 3.8 min vs. 81.6 + 2.8 min) (p = 0.006). Conclusions: Cavity shaving after lumpectomy reduced the rate of positive margins and it was associated with a significant reduction in surgical time compared to intraoperative evaluation of resection margins.

Blood-Derived Systemic Inflammation Markers and Risk of Nodal Failure in Stage Ia Non-Small Cell Lung Cancer: A Multicentric Study.

BACKGROUND: Unexpected spread to regional lymph nodes can be found in up to 10% of patients with early stage non-small cell lung cancer (NSCLC), thereby affecting both prognosis and treatment. Given the known relation between systemic inflammation and tumor progression, we sought to evaluate whether blood-derived systemic inflammation markers might help to the predict nodal outcome in patients with stage Ia NSCLC. METHODS: Preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation score (SII, platelets × NLR) were collected from 368 patients who underwent curative lung resection for NSCLC. After categorization, inflammatory markers were subjected to logistic regression and time-event analysis in order to find associations with occult nodal spread and postoperative nodal recurrence. RESULTS: No inflammation marker was associated with the risk of occult nodal spread. SII showed a marginal effect on early nodal recurrence at a quasi-significant level (p = 0.065). However, patients with T1c tumors and elevated PLR and/or SII had significantly shorter times to nodal recurrence compared to T1a/T1b patients (p = 0.001), while patients with T1c and normal PLR/SII did not (p = 0.128). CONCLUSIONS: blood-derived inflammation markers had no value in the preoperative prediction of nodal status. Nevertheless, our results might suggest a modulating effect of platelet-derived inflammation markers on nodal progression after the resection of tumors larger than 2 cm.

The effectiveness of chest T-tube drainage in uniportal video-assisted thoracic surgery.

OBJECTIVES: Uniportal incision located at 4th or 5th intercostal space represents a problem for the correct drainage of distal areas of pleural cavity. The T-shaped tube can drain both the extremities of pleural space. In this study, we evaluated the effectiveness of T-chest tube compared to classic chest tube after uniportal video-assisted thoracic surgery. METHODS: We compared the effectiveness of T-tube and classic 28 CH chest drainage after different surgical procedures in uniportal video-assisted thoracic surgery: lobectomies, wedge resections and pleural and mediastinal biopsies. As primary end points, drained effusion and evidence of pneumothorax at postoperative day 1, subcutaneous emphysema, tube kinking, obstruction and necessity of repositioning or postoperative thoracentesis were considered. Pain at 6 and 24 h after surgery, pain at tube removal and mean hospitalization were analysed as secondary end points. RESULTS: A total of 109 patients were selected for the study, 51 included to the T-tube group while the other 58 ones to the control group with classic drainage. Patients with T-tube showed a significantly lower rate of pneumothorax (29.4% vs 63.8%; P < 0.001), tube kinking (5.9% vs 27.6%; P = 0.003) and need of repositioning (2.0% vs 12.1%; P = 0.043). No significant results were obtained in subcutaneous emphysema (P = 0.26), tube obstruction (P = 0.32), drained effusion (P = 0.11) and need of postoperative thoracentesis (P = 0.18). Patients with T-tube complained of <6 h after surgery (P < 0.001). Conversely, T-tube removal was reported to be more painful (P < 0.001). CONCLUSIONS: Chest T-tube can achieve significantly lower rate of postoperative pneumothorax, kinking and repositioning with less pain 6 hours after surgery compared to classic tube.

Anxiety and Fear of Breast Cancer Patients During and After the COVID-19 Era.

BACKGROUND/AIM: Coronavirus-19 (COVID-19) pandemic had a huge impact on medical resource allocation. While it is clear that the surgery refusal rate of patients with breast cancer (BC) was higher during the pandemic, long-term effect of COVID-19 pandemic on hospital admission in the post-pandemic period has not been fully evaluated. This study aimed to estimate how patients' behavior changed following the pandemic and whether the cross-infection risk is still influencing patients' decision-making process. PATIENTS AND METHODS: Between the 16th of January and 18th of March 2020, between 19th of March 2020 and the 20th of March 2020, and between 19th of March 2023 and the 20th of March 2023, 266 patients were enrolled and divided into PRE-COVID-19, COVID-19, and POST-COVID-19 groups, respectively. A total of 137 patients with a suspected breast lesion (SBL) were divided into 3 groups: PRE-COVID-19-SBL, COVID-19-SBL, and POST-COVID-19-SBL groups. In addition, 129 BC patients were divided into PRE-COVID-19-BC, COVID-19-BC and POST-COVID-19-BC groups. Patient characteristics including age, marital status, SBL/BC diameter, personal and family history of BC, clinical stage and molecular subtype were recorded. Procedure refusal (PR) and Surgical refusal (SR) were also recorded with their reason. RESULTS: BC and SBL analysis showed no difference in pre-treatment characteristics (p>0.05). While higher rate of PR and SR rates were reported in COVID-19-SBL and COVID-19-BC groups when compared with PRE-COVID-19 (p=0.003, p=0.013, respectively) and POST-COVID-19 (p=0.005, p=0.004, respectively) groups, no statistical difference was found between PRE-COVID-19 and POST-COVID-19 subanalysis. CONCLUSION: Thanks to preventive measures, COVID-19 does not currently seem to affect the decision-making process of patients with BC.

Awake Breast Conservative Surgery: A Strategy to Shorten Surgical Waiting Lists During and Post COVID-19 Emergency.

BACKGROUND/AIM: SARS-CoV-2 with a dramatical worldwide spread, impacted greatly daily life and healthcare. In order to avoid delay in cancer treatment, many strategies and measures were implemented. The Awake breast surgery was a strategy implemented in our Unit during the pandemic, aimed to reduce operatory room occupancy and increase the number of procedures performed during the daily surgical session. The aim of the study was to evaluate how the use of this strategy has changed before and after the advent of the COVID-19 pandemic, and its relative benefits. PATIENTS AND METHODS: This was a retrospective study analysing all patients subjected to breast conservative surgery for oncological disease from July 2018 to December 2021. RESULTS: Out of 498 patients enrolled in the study, 253 (50.8%) cases were treated before the pandemic and were designated as "pre-COVID-19" group. The remaining 245 (49.1%) cases were considered the "COVID-19" group. Cases of awake surgery in COVID-19 group were 141 (54.7%) vs. 84 (33.2%), p<0.001. Length of hospitalization and surgical time were comparable between the groups: relative p=0.188 and 0.264, respectively. Differently, operation room occupation was significantly shorter in the COVID-19 group, p<0.001; and number of outpatient surgical procedures was higher, p=0.0304. Multivariate analysis identified the period of surgery (OR=1.47) as a statistically significant factor, p=0.011, predictive of prolonged operatory room occupancy. CONCLUSION: Awake surgery was one of the strategies which made more operating rooms available and allowed avoiding further delays.

Systemic Inflammation after Uniport, Multiport, or Hybrid VATS Lobectomy for Lung Cancer.

BACKGROUND: Different video-assisted thoracic surgery (VATS) approaches can be adopted to perform lobectomy for non-small cell lung cancer. Given the hypothetical link existing between postoperative inflammation and long-term outcomes, we compared the dynamics of systemic inflammation markers after VATS lobectomy performed with uniportal access (UNIVATS), multiportal access (MVATS), or hybrid approach (minimally invasive hybrid open surgery, MIHOS). METHODS: Peripheral blood-derived inflammation markers (neutrophil-to-lymphocyte [NTL] ratio, platelet-to-lymphocyte [PTL] ratio, and systemic immune-inflammation index [SII]) were measured preoperatively and until postoperative day 5 in 109 patients undergoing UNIVATS, MVATS, or MIHOS lobectomy. Differences were compared through repeated-measure analysis of variance, before and after 1:1:1 propensity score matching. Time-to-event analysis was also done by measuring time to NTL normalization, based on the reliability change index for each patient. RESULTS: After UNIVATS, there was a faster decrease in NTL ratio (p = 0.015) and SII (p = 0.019) compared with other approaches. MVATS exhibited more pronounced PTL rebound (p = 0.011). However, all these differences disappeared in matched analysis. After MIHOS, NTL ratio normalization took longer (mean difference: 0.7 ± 0.2 days, p = 0.047), yet MIHOS was not independently associated with slower normalization at Cox's regression analysis (p = 0.255, odds ratio: 1.6, confidence interval: 0.7-4.0). Furthermore, surgical access was not associated with cumulative postoperative morbidity, nor was it with incidence of postoperative pneumonia. CONCLUSION: In this study, different VATS approaches resulted into unsubstantial differences in postoperative systemic inflammatory response, after adjusting for confounders. The majority of patients returned back to preoperative values by postoperative day 5 independently on the adopted surgical access. Further studies are needed to elaborate whether these small differences may still be relevant to patient management.

Pre-pectoral Breast Reconstruction Does Not Affect Early Immunological Response: A BIAL 2.20 Study Subanalysis.

BACKGROUND/AIM: Reduction of postoperative stress is a modern tenet in surgical oncology with the aim of reducing early postoperative lymphopenia. Our prospective study evaluated post-operative immune response at baseline and postoperative day (POD) 1 and 2 after direct-to-implant pre-pectoral (PP) breast reconstruction with titanium-coated polypropylene mesh versus subpectoral (SP) breast reconstruction. PATIENTS AND METHODS: Between January and December 2020, 37 patients were randomized between PP (n=17) or SP (n=16) reconstruction. Baseline and operative data were analyzed. Postoperative pain assessment using numeric pain rating scale (NPRS), and a full blood count with lymphocyte subsets were collected before surgery, and on POD1 and POD2. Data were evaluated by two-way analysis of variance test. RESULTS: Baseline data did not demonstrate any statistical difference. Inter-group analysis did not provide any statistically significant difference in leukocytes, total lymphocytes, and lymphocytes subsets among SP and PP reconstruction groups (p>0.05). However, compared to specificity, the PP group experienced shorter operative time, with a mean difference 30.19 min, lower blood loss (p=0.017), lower rate of postoperative anemia (p=0.039), and a more favorable profile in inter-group pain analysis (p<0.001). CONCLUSION: PP reconstruction with titanium-coated polypropylene mesh does not increase immunological impairment in the early postoperative period when compared with SP reconstruction and provides lower postoperative pain, reduction of operative time, and lower rate of postoperative anemia.

Breast Textured Implants Determine Early T-helper Impairment: BIAL2.20 Study.

BACKGROUND/AIM: Surgical stress has been correlated with higher rate of postoperative complications. Breast implants' surfaces (textured or smooth) represent an immunological stimulus. Our prospective study (BIAL2.20) evaluated post-operative leukocytes response at baseline and postoperative day (POD) 1 and 2 after implant-based breast reconstruction. PATIENTS AND METHODS: Between January and July 2020, 41 patients underwent reconstruction with textured (n=23) or smooth (n=18) implants. A full blood count and lymphocyte subsets were collected before surgery, on POD1 and POD2. Data were evaluated as difference and relative difference from baseline by two-way analysis of variance test (2-way-ANOVA). Mann-Whitney U-test was performed at each POD, whenever between-group 2-way-ANOVA reached statistical significance. RESULTS: Within-group-analysis showed statistically significant total leukocytosis in both groups. Within-group-analysis of lymphocytes subsets demonstrated statistically significant lymphopenia in the textured group for T-lymphocytes, and T-helper cells. Between-group-analysis showed statistically significant lymphopenia in T-helper subsets in the textured group at POD1 and POD2, when compared with the smooth group. CONCLUSION: Textured implants demonstrated a statistically significant impairment of T-helper trend during POD1 and POD2 when compared to smooth implants by between-group 2-way-ANOVA.

Off-Label Use of T-Tube as Chest Drainage for Uniportal Surgery.

Uniportal video-assisted thoracic surgery implies the positioning of a single chest drain at the mid thorax level. Therefore, this tube cannot reach simultaneously the basal and apical regions of the pleural cavity. We propose the off-label use of a T-tube usually utilized in biliary duct surgery. Despite mid thorax insertion, this tube allows effective air and fluid drainage of the entire pleural space. We tested it in 10 patients undergoing uniportal surgery and report satisfactory results. No postoperative chest tube displacement, pleural effusion infection, or subatelectasies occurred. We conclude that the T-tube represents a good alternative in patients at high risk of postoperative effusion undergoing the uniportal approach.

Case Report: Early Breast Cancer Recurrence Mimicking BIA-ALCL in a Patient With Multiple Breast Procedures.

Breast reconstruction plays a fundamental role in the therapeutic process of breast cancer treatment and breast implants represents the leading breast reconstruction strategy. Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL), locoregional recurrence in the skin flap, and skin flap necrosis are well-known complications following mastectomy and immediate breast reconstruction (IBR). We report a case of locoregional cancer recurrence in the mastectomy flap mimicking BIA-ALCL, in a patient who underwent 6 breast procedures in four facilities across 15 years including immediate breast reconstruction with macrotextured breast implants. Despite the rate and onset of the disease, clinicians should be aware of BIA-ALCL. Due to the risk of false negative results of fine needle aspiration, clinical suspicion of BIA-ALCL should drive clinicians' choices, aside from cytological results. In the present case, surgical capsulectomy of the abnormal periprosthesic tissue revealed locoregional recurrence.

Real-Time Pleural Elastography: Potential Usefulness in Nonintubated Video-Assisted Thoracic Surgery.

Pleural adhesions are a major challenge in standard and nonintubated video-assisted thoracic surgery. The currently available imaging techniques help to assess the presence and extent of pleural adhesions, but do not provide information on tissue deformability, which is crucial for intraoperative management. In this report, we describe the utilization of real-time elastography mapping of pleural adhesions. This technique enabled us to detect areas with softer adhesions, and helped establish the surgical plan in a difficult case of a patient scheduled for nonintubated video-assisted thoracic surgery.

Thoracic surgery in the COVID-19 era: an Italian university hospital experience.

Background: Aims of this study were to assess the results of anti-COVID19 measures applied to maintain thoracic surgery activity at an Italian University institution through a 12-month period and to assess the results as compared with an equivalent non-pandemic time span. Methods: Data and results of 646 patients operated on at the department of Thoracic Surgery of the Tor Vergata University Policlinic in Rome between February 2019 and March 2021 were retrospectively analyzed. Patients were divided in 2 groups: one operated on during the COVID-19 pandemic (pandemic group) and another during the previous non-pandemic 12 months (non-pandemic group). Primary outcome measure was COVID-19 infection-free rate. Results: Three patients developed mild COVID-19 infection early after surgery resulting in an estimated COVID-19 infection-free rate of 98%. At intergroup comparisons (non-pandemic vs. pandemic group), a greater number of patients was operated before the pandemic (352 vs. 294, p = 0.0013). In addition, a significant greater thoracoscopy/thoracotomy procedures rate was found in the pandemic group (97/151 vs. 82/81, p = 0.02) and the total number of chest drainages (104 vs. 131, p = 0.0001) was higher in the same group. At surgery, tumor size was larger (19.5 ± 13 vs. 28.2 ± 21; p < 0.001) and T3-T4/T1-T2 ratio was higher (16/97 vs. 30/56; p < 0.001) during the pandemic with no difference in mortality and morbidity. In addition, the number of patients lost before treatment was higher in the pandemic group (8 vs. 15; p = 0.01). Finally, in 7 patients admitted for COVID-19 pneumonia, incidental lung (N = 5) or mediastinal (N = 2) tumors were discovered at the chest computed tomography. Conclusions: Estimated COVID-19 infection free rate was 98% in the COVID-19 pandemic group; there were less surgical procedures, and operated lung tumors had larger size and more advanced stages than in the non-pandemic group. Nonetheless, hospital stay was reduced with comparable mortality and morbidity. Our study results may help implement efficacy of the everyday surgical care.

Subxiphoid completion thymectomy for refractory non-thymomatous myasthenia gravis.

BACKGROUND: Completion thymectomy may be performed in patients with non-thymomatous refractory myasthenia gravis (MG) to allow a complete and definitive clearance from residual thymic tissue located in the mediastinum or in lower neck. Hereby we present our short- and long-term results of completion thymectomy using subxiphoid video-assisted thoracoscopy. METHODS: Between July 2010 and December 2017, 15 consecutive patients with refractory non-thymomatous myasthenia, 8 women and 7 men with a median age of 44 [interquartile range (IQR) 38.5-53.5] years, underwent video-thoracoscopic completion thymectomy through a subxiphoid approach. RESULTS: Positron emission tomography (PET) showed mildly avid areas [standardized uptake value (SUV) more than or equal to 1.8] in 11 instances. Median operative time was 106 (IQR, 77-141) minutes. No operative deaths nor major morbidity occurred. Mean 1-day postoperative Visual Analogue Scale value was 2.53±0.63. Median hospital stay was 2 (IQR, 1-3.5) days. A significant decrease of the anti-acetylcholine receptor antibodies was observed after 1 month [median percentage changes -67% (IQR, -39% to -83%)]. Median follow-up was 45 (IQR, 21-58) months. At the most recent follow-up complete stable remission was achieved in 5 patients. Another 9 patients had significant improvement in bulbar and limb function, requiring lower doses of corticosteroids and anticholinesterase drugs. Only one patient remained clinically stable albeit drug doses were reduced. One-month postoperative drop of anti-acetylcholine receptor antibodies was significantly correlated with complete stable remission (P=0.002). CONCLUSIONS: This initial experience confirms that removal of ectopic and residual thymus through a subxiphoid approach can reduce anti-acetylcholine receptor antibody titer correlating to good outcome of refractory MG.

Team Training for Nonintubated Thoracic Surgery.

Nonintubated thoracic surgery arose as supplemental evolution of minimally invasive surgery and is gaining popularity. A proper nonintubated thoracic surgery unit is mandatory and should involve surgeons, anesthesiologists, intensive care physicians, physiotherapists, psychologists, and scrub and ward nurses. Surgical training should involve experienced and young surgeons. It deserves a step-by-step approach and consolidated experience on video-assisted thoracic surgery. Due to difficulty in reproducing lung and diaphragm movements, training with simulation systems may be of scant value; instead, preceptorships and invited proctorships are useful. Preoperatively, patients must be fully informed. Effective intraoperative communication with patients and among the surgical team is pivotal.

Impact of Awake Breast Cancer Surgery on Postoperative Lymphocyte Responses.

BACKGROUND: Surgical stress and anesthesia affect the patient's immune system. Analysis of the lymphocyte response after breast-conserving surgery was conducted to investigate the differences between effects after general and local anesthesia. MATERIALS AND METHODS: Fifty-six patients with breast cancer were enrolled for BCS through local or general anesthesia. Total leukocytes, total lymphocytes, lymphocyte-subsets including CD3+, CD19+, CD4+, CD8+, CD16+CD56+ and CD4+/CD8+ ratio was examined at baseline and on postoperative days 1, 2 and 3. RESULTS: Baseline data showed no statistical difference between the two groups. Within-group ANOVA test showed significant differences for total leukocyte count (p<0.001), total lymphocyte count (p=0.009) and proportion of natural-killer cells (p=0.01) in the control group. Between-group analysis showed lower median values of total lymphocytes in the awake surgery group on postoperative days 1, 2 and 3 (p=0.001, p=0.02 and p=0.01, respectively) when compared to the control group. Patients who underwent surgery under general anesthesia had higher total lymphocyte counts on postoperative day 2 (p=0.04). CONCLUSION: In this randomized study, breast-conserving surgery plus local anesthesia had a lower impact on postoperative lymphocyte response when compared to the same procedure performed under general anesthesia.