Nanotechnologies in Obstetrics and Cancer during Pregnancy: A Narrative Review.

Nanotechnology, the art of engineering structures on a molecular level, offers the opportunity to implement new strategies for the diagnosis and management of pregnancy-related disorders. This review aims to summarize the current state of nanotechnology in obstetrics and cancer in pregnancy, focusing on existing and potential applications, and provides insights on safety and future directions. A systematic and comprehensive literature assessment was performed, querying the following databases: PubMed/Medline, Scopus, and Endbase. The databases were searched from their inception to 22 March 2022. Five independent reviewers screened the items and extracted those which were more pertinent within the scope of this review. Although nanotechnology has been on the bench for many years, most of the studies in obstetrics are preclinical. Ongoing research spans from the development of diagnostic tools, including optimized strategies to selectively confine contrast agents in the maternal bloodstream and approaches to improve diagnostics tests to be used in obstetrics, to the synthesis of innovative delivery nanosystems for therapeutic interventions. Using nanotechnology to achieve spatial and temporal control over the delivery of therapeutic agents (e.g., commonly used drugs, more recently defined formulations, or gene therapy-based approaches) offers significant advantages, including the possibility to target specific cells/tissues of interest (e.g., the maternal bloodstream, uterus wall, or fetal compartment). This characteristic of nanotechnology-driven therapy reduces side effects and the amount of therapeutic agent used. However, nanotoxicology appears to be a significant obstacle to adopting these technologies in clinical therapeutic praxis. Further research is needed in order to improve these techniques, as they have tremendous potential to improve the accuracy of the tests applied in clinical praxis. This review showed the increasing interest in nanotechnology applications in obstetrics disorders and pregnancy-related pathologies to improve the diagnostic algorithms, monitor pregnancy-related diseases, and implement new treatment strategies.

One-Step Nucleic Acid Amplification System in Comparison to the Intraoperative Frozen Section and Definitive Histological Examination Among Breast Cancer Patients: A Retrospective Survival Study.

Simple Summary: Implementing intraoperative assessment of sentinel lymph nodes by one-step nucleic acid amplification in early breast cancer can reduce the surgical burden to the patient and the costs to the health system. However, only limited data are available in terms of long-term disease-free survival and overall survival. Therefore, this study aims to compare disease-free survival and overall survival between one-step nucleic acid amplification, frozen section, and definitive histology. These results could impact the healthcare community, adding further proof to the body of evidence supporting the broader adoption of this innovative technology that enables a safe reduction in patient surgical burden and healthcare costs. Background: The one-step nucleic acid amplification (OSNA) system is a novel molecular technique, which consents to quick intraoperative detection of sentinel lymph node metastases by the amplification of cytokeratin 19 mRNA. Our study aims to evaluate the OSNA method in comparison with frozen section (FS) and definitive histological examination of the sentinel lymph node biopsy among early breast cancer patients considering disease-free survival (DFS) and overall survival (OS). Methods: In this study, we included all women who underwent sentinel lymph node biopsy (SLNB) for breast cancers classified as TNM stage I and II in our center between January 2005 and January 2017, and the follow-up was collected up to January 2019. We divided patients among three groups based on SLNB evaluation: definitive histological examination, intra-operative FS, or OSNA. Results: We included 2412 SLNBs: 727 by definitive histological examination, 697 by FS, and 988 by OSNA. Isolated tumor cells were found in 2.32% of cases, micrometastasis in 9.12%, and macrometastases in 13.64%. Surgical procedure duration was significantly shorter in OSNA than in FS (42.1 minutes ±5.1 vs. 70.1 minutes ±10.5, p <0.05). No significant differences have been observed among the three groups regarding OS, DSF, cumulative local, or distant metastases. In particular 5-year DFS was 96.38% in definitive histology (95% C.I. 95.02-97.75%), 96.37% in FS (95% C.I. 94.98-97.78%), and 96.51% in OSNA group (95% C.I. 95.32-97.72%). Conclusions: No difference in OS and DFS was found comparing OSNA, FS, and definitive histology. Furthermore, reduced operative time was found in the OSNA group.

Multidisciplinary Team Meeting Proposal and Final Therapeutic Choice in Early Breast Cancer: Is There an Agreement?

Background: A multidisciplinary team meeting (MDM) approach in breast cancer (BC) management is a standard of care. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early BC. The purpose of this study was to define whether there was an agreement between the planned program (i.e., MDMs-based decision) and that actually applied. In addition, the study explored factors associated with discordance. Methods: We conducted a retrospective study of a consecutive series of 291 patients with new diagnosis of early BC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. The association between clinico-biological factors and discordance between what was decided during the MDMs and what was consequently applied by the oncologist was explored through uni- and multivariate logistic regression analyses. Results: The median age was 62 years (range 27-88 years). Among invasive early BC patients, the most frequent phenotype was luminal A (38%), followed by luminal B (33%), HER2-positive (12%), and triple-negative (5%). In situ carcinoma (DCIS) represented 12% of cases. The median time from MDM discussion to first oncologic examination was 2 weeks. The rate of discordance between MDM-based decision and final choice, during a face-to-face consultation with the oncologist, was 15.8% (46/291). The most frequent reason for changing the MDM-based program was clinical decision (87%). Follow-up was preferred to the chemotherapy (CT) proposed within the MDMs in 15% of cases, and to the endocrine therapy (ET) in 39% of cases (among these, 44.5% had a diagnosis of DCIS). Therapeutic change from sequential CT-ET to ET alone was chosen in 16/46 pts (35%): among these patients, seven had a luminal B disease and six had an HER2-positive disease. On univariate analysis, factors associated with discordance were values of Ki-67 14%-30% (OR 3.91; 95% CI 1.19-12.9), age >70 years (OR 2.44, 95% CI 1.28-4.63), housewife/retired status (OR 2.35, 95% CI 1.14-4.85), polypharmacy (OR 1.95; 95% CI 1.02-3.72), postmenopausal status (OR 4.15; 95% CI 1.58-10.9), and high Charlson Comorbidity Index (OR 1.31; 95% CI 1.09-1.57). The association with marital status, educational level, alcohol and smoke habits, presence of a caregiver, parity, grading, histotype and phenotype, and stage was not statistically significant. On multivariate analysis, only Ki-67 value maintained its statistical significance. Conclusion: The results of our study could be useful for enhancing the role of MDMs in the clinical decision-making process in early BC.

Patient-reported pain and other symptoms among breast cancer survivors: prevalence and risk factors.

OBJECTIVE: To investigate the prevalence and risk factors associated with chronic pain and other symptoms related to breast cancer 6 months after surgery. METHODS: In an observational study of 261 female breast cancer survivors treated between January 2017 and January 2018, patients were asked about their pain symptoms using a questionnaire that utilized the Numeric Rating Score (NRS) and the Douleur Neuropathique Score (DN4) for neuropathic pain; it also addressed phantom sensations and functional disorders on the ipsilateral shoulder. A total of 218 women completed the survey. RESULTS: A total of 105 patients (48.17%) reported chronic pain. Of these, 64% rated the pain with an NRS of 1-3 and 35% with an NRS >3. Neuropathic pain was reported in 65% of the sample, phantom sensations in 12%, disorders of shoulder function in 16%, and web syndrome in 2%. Multivariable analyses showed that chronic pain (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.094-5.942; p < 0.05) and neuropathic pain (OR, 2.988; 95% CI, 1.366-6.537; p < 0.05) were positively associated with surgical adverse events; phantom sensations were statistically associated with the weight of removed breast tissue (OR, 1.003; 95% CI, 1.001-1.005; p < 0.05). CONCLUSIONS: Our study highlights the need to employ specific tools capable of detecting different kinds of chronic pain after breast cancer surgery to improve pain prevention and treatment. Surgical complications and the weight of removed breast tissue emerged as 2 of the risk factors for chronic and neuropathic pain development in breast cancer survivors.

Does the status of surgical resident compared to that of consultant have an impact on patient's satisfaction over the informed consent process?

OBJECTIVE: The informed consent process is a fundamental element of best practice in the surgical patient's care. The aim of the present study is to investigate the value of informed consent from the patient's perspective in a Teaching Hospital. In particular, the role of the Residents within this process is analyzed to compare their performance with that of Consultants. DESIGN: This is a prospective observational study based on a consecutive cohort of patients who were offered an elective surgical procedure during the period April 2015 - September 2015. SETTING: The study was conducted in the Surgical and Transplantation Unit of the University Hospital of Udine, Italy, accredited by the Joint Commission International. PARTICIPANTS: The study population consisted of 236 patients. The participants were asked on a voluntary basis to fill in a self-evaluating questionnaire after being requested to complete a written informed consent before the operation. RESULTS: In the present study we didn't register any significant difference of patient's satisfaction over informed consent when we evaluated the performance of Residents in comparison to Consultants. CONCLUSIONS: We believe that our positive results may be related to our educational training approach. However, adequate education of Residents about seeking informed consent is not sufficient to guarantee an effective informed consent process if it is not supported as a counterpart by the promotion of correct and positive patient knowledge and perception of the Residents' skills, clinical role and responsibilities. KEY WORDS: Educational program, Informed consent, Informed consent process, Patient's satisfaction, Resident.

Clinical strategies to aim an adequate safety profile for patients and effective training for surgical residents: The laparoscopic cholecystectomy model.

BACKGROUND: Training programs for resident surgeons represent a challenge for the mentoring activity. The aim of the present study is to investigate the impact of our training program for laparoscopic cholecystectomy on patient's safety and on the modulation of the residents' exposure to clinical scenario with different grades of complexity. MATERIAL AND METHODS: This is a retrospective study based on a clinical series of laparoscopic cholecystectomy performed in a teaching hospital. Study population was grouped according to the expertise of the attending primary operator among resident surgeons. Four groups were identified: consultant (C), senior resident (SR); intermediate level resident (IR); junior resident (JR). The intraoperative and postoperative outcomes were confronted to evaluate the patient's safety profile. RESULTS: 447 patients were submitted to LC: 96 cases were operated by a C, 200 by SR, 112 by IR and 39 by JR. The mean operative time was the longest for the JR group. A statistically higher rate of conversion to open approach was registered in C and IR groups in comparison to JR and SR groups. However, in C and IR groups, patients had worse ASA score, higher BMI and more frequent past history of previous abdominal surgery, cholecystitis or pancreatitis. Overall, it was not registered any statistically significant difference among the groups in terms of length of hospital stay and prevalence of major postoperative complications. CONCLUSION: Applying an educational model based on both graduated levels of responsibility and modulated grade of clinical complexity can guarantee an high safety profile.

Prevalence, risk factors, and prognosis of peritoneal metastasis from breast cancer.

Peritoneal metastasis from breast cancer is a serious and deadly condition only limited considered in the literature. Our aim was to study prevalence, risk factors, and prognosis of breast cancer peritoneal metastasis. We retrospectively analyzed 3096 women with a diagnosis of invasive breast cancer. We took into consideration presence and localization of breast cancer distant metastasis as well as the possible risk factors and survival from the diagnosis of the breast cancer metastasis. The prevalence of breast cancer peritoneal metastases was 0.7 % (22/3096), representing the 7.6 % (22/289) of women affected by distant metastases. Moreover, independent risk factors for breast cancer peritoneal metastases resulted high grading, lobular invasive histology, and advanced T and N stage at diagnosis. Overall survival after metastasis diagnosis was shorter in women affected by peritoneal metastases or brain metastases in comparison to other metastatic women. Breast cancer peritoneal metastases were uncommon but not rare events with a poor prognosis after standard treatments.

Impact of the presence and quantity of ductal carcinoma in situ component on the outcome of invasive breast cancer.

INTRODUCTION: The role of ductal carcinoma in situ (DCIS) component on the outcome of invasive breast cancer is not yet completely clear. Our study aims to assess the impact of the presence and quantity of DCIS component on the outcome of patients operated for invasive breast cancer. MATERIALS AND METHODS: We collected retrospective data about patients operated at their breast for invasive cancer between 2007 and 2012, focusing on the presence of DCIS component. Then, we divided patients into four groups based on the quantity of DCIS component as follows: not found (group A), minimal (group B, <25%), extensive (group C, 25-75%), and prevalent (group D, >75%). We further defined "extensive intraductal component" (EIC) groups C and D together. RESULTS: DCIS component was associated with young age, familial history of breast cancer and worse biological characteristics, including high grading, higher prevalence of Her2/Neu overexpression, hormone receptors negativity, comedo-like necrosis and multifocality/multicentricity. Despite the unfavorable prognostic factors, invasive cancers associated with EIC were frequently treated with radical surgery and resulted to have long disease-free survival and low local recurrence rate. In patients with DCIS component (groups B, C, and D) the extension of this component resulted indirectly correlated with local recurrence rate, tumor lymphovascular invasion, and lymphnode extracapsular invasion. The highest prevalence of local recurrences was found in group B, which tended to be less frequently treated with radical surgery than group D (P<0.05) and C (P=n.s.). CONCLUSIONS: Different clinical and tumor features among invasive breast cancer with and without DCIS component indicate that they are distinct entities probably originating by different pathways that deserve to be studied. Furthermore, the controversial results about the management of cancer with minimal intraductal component require further studies in order to reduce local recurrence.

Type of breast cancer diagnosis, screening, and survival.

INTRODUCTION: Breast cancer screening is known to reduce mortality. In the present study, we analyzed the prevalence of breast cancers detected through screening, before and after introduction of an organized screening, and we evaluated the overall survival of these patients in comparison with women with an extrascreening imaging-detected breast cancer or those with palpable breast cancers. MATERIALS AND METHODS: We collected data about all women who underwent a breast operation for cancer in our department between 2001 and 2008, focusing on type of tumor diagnosis, tumor characteristics, therapies administered, and patient outcome in terms of overall survival, and recurrences. Data was analyzed by R (version 2.15.2), and P < .05 was considered significant. RESULTS: Among the 2070 cases of invasive breast cancer we considered, 157 were detected by regional mammographic screening (group A), 843 by extrascreening breast imaging (group B: 507 by mammography and 336 by ultrasound), and 1070 by extrascreening breast objective examination (group C). The 5-year overall survival in groups A, B, and C were, respectively, 99% (95% CI, 98%-100%), 98% (95% CI, 97%-99%), and 91% (95% CI, 90%-93%), with a significant difference between the first 2 groups and the third (P < .05) and a trend between groups A and B (P = .081). CONCLUSION: The diagnosis of invasive breast cancer with screening in our population resulted in a survival gain at 5 years from the diagnosis, but a longer follow-up is necessary to confirm this data.

Feasibility of concervative breast surgery and intraoperative radiation therapy for early breast cancer: a single-center, open, non-randomized, prospective pilot study.

Intraoperative radiotherapy (IORT) consists of an accelerated, single-dose, partial breast irradiation, performed immediately after breast conservative surgery. In the present study, we report the results of our feasibility protocol study using IORT between 2005 and 2009. We analyzed the data from a single-center, open, non-randomized, prospective pilot study including patients who underwent breast conservative surgery for invasive breast cancer between January 2005 and December 2009 at our Clinic of Surgery. Patients were divided based on IORT performance and stratified by age (≥48 or <48 years). Data were analyzed using R (version 2.15.2), considering a level of significance at p<0.05. Among the 247 eligible patients, 81 accepted the IORT protocol. Intraoperative IORT feasibility was 95.1% (77/81). In 71.4% (55/77) of the cases no postoperative complication was registered. Concerning local recurrence and overall survival, no significant difference was observed between women who underwent the IORT protocol or standard treatment. Among the patients aged <48 years, no local recurrence was noted after IORT protocol, and among women aged ≥48, local recurrences developed later in patients treated with IORT than with standard treatment. IORT represents a feasible and promising technique for the treatment of early breast cancer, with low morbidity, and beneficial aesthetic and oncologic results. Further studies are required in order to extend the inclusion criteria and offer IORT to a larger number of breast cancer patients.

Eight-year experience with the intraoperative frozen section examination of sentinel lymph node biopsy for breast cancer in a North-Italian university center.

Sentinel lymph node biopsy (SLNB) completely changed the impact of breast surgery on patients psycho-physical wellness, reducing morbidity associated with complete axillary lymph node dissection (CALND) while granting an adequate breast cancer staging. We reviewed our experience with the SLNB in a University Clinic. We collected data about all breast cancer patients submitted to SLNB from 2002 to 2010, and analyzed them with R (version 2.15.2), considering significant p<0.05. We performed 615 SLNBs on 607 patients, with a mean age of 59.86 (±10.76). Sentinel node detection rate resulted 99,7%, with a mean number of biopsied nodes of 1.64 (±0.67), axillary localization in 98% of cases, and negative intraoperative histological finding in the 86.2% of cases. Prevalence of ITCs, micrometastasis, macrometastasis and pericapsular metastasis resulted respectively 0.6%, 4.9%, 7.5% and 8.8%. Among women who received CALND, mean number of examined nodes was 16.36 (±6.19) and mean number of metastatic non-sentinel nodes was 0.97 in case of micrometastasis, 2.65 in case of macrometastasis, and up to 9.88 when pericapsular invasion was described. To conclude, our data confirm the role of nodal metastasis size in the prediction of non-sentinel node involvement, but further studies are required in order to better assess the role of ITCs and micrometastasis in the diagnostic and therapeutic management of breast cancer, with the final aim to reduce the surgical complications of axilla demolition when unnecessary.