Oncological Outcomes of Nipple-Sparing Mastectomy: A Single-Center Experience of 1989 Patients.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly used in women with breast cancer who are not eligible for conservative surgery, but extensive outcome data are lacking and indications have not been established. OBJECTIVE: The aim of this study was to assess the oncological outcomes of NSM in a large series of patients with invasive or in situ breast cancer treated at a single center. METHODS: We analyzed 1989 consecutive women who had an NSM in 2003-2011, for invasive (1711 patients) or in situ cancer (278 patients) at the European Institute of Oncology, Italy, and followed-up to December 2016. Endpoints were local recurrences, recurrences in the nipple-areola complex (NAC), NAC necrosis, and overall survival (OS). RESULTS: After a median follow-up of 94 months (interquartile range 70-117), 91/1711 (5.3%) patients with invasive cancer had local recurrence (4.8% invasive disease, 0.5% in situ disease), and 11/278 (4.0%) patients with in situ disease had local recurrence (1.8% invasive disease, 2.2% in situ disease). Thirty-six (1.8%) patients had NAC recurrence, 9 with in situ disease (4 invasive and 5 in situ recurrences), and 27 with invasive disease (18 invasive and 9 in situ recurrences). NAC loss for necrosis occurred in 66 (3.3%) patients. There were 131 (6.6%) deaths, 109 (5.5%) as a result of breast cancer. OS at 5 years was 96.1% in women with invasive cancer and 99.2% in women with in situ disease. CONCLUSIONS: The findings in this large series, with a median follow-up of nearly 8 years, indicate that NSM is oncologically safe for selected patients. The rate of NAC loss was acceptably low.

The impact of laparoscopic Nissen fundoplication on the long-term quality of life in patients with gastroesophageal reflux disease.

Laparoscopic Nissen fundoplication is now the most common surgical procedure for treatment of gastroesophageal reflux disease (GERD), offering promising long-term outcomes. Outcomes for 46 patients with GERD who underwent Nissen fundoplication during the last 5 years (November 2007-June 2012) were prospectively studied using a structured questionnaire that evaluated clinical symptom scores for heartburn, dysphagia, and satisfaction with clinical outcomes. Postoperative care of the patients including analgesia, median hospital stay, overall cost, and complications was also studied. Clinical follow-up data for 2 years after surgery were available for all 46 patients. Forty-two patients (91.3%) were satisfied with their quality of life and only eight patients (17.4%) continued to receive antacids after surgery. Dysphagia to solid and liquid occasionally appeared in 26.1% (N = 12) and 17.4% (N = 8) of patients, respectively. Laparoscopic Nissen fundoplication was an effective long-term treatment for GERD. The operation resulted in a significant reduction of symptoms and minimized the use of antacid drugs with a high degree of patient satisfaction. Although some patients may have returned to antacid treatment at late follow-up or continued to complain of mild discomfort, they were overall pleased with the outcome.

CDH1 germline mutations in families with hereditary lobular breast cancer.

Pathogenic CDH1 germline mutations are associated with lobular breast cancer in the so-called hereditary lobular breast cancer (HLBC) syndrome, without apparent correlation with the classic hereditary diffuse gastric cancer (HDGC). Recent international guidelines recommend CDH1 screening also in absence of diffuse gastric cancer (DGC) history. Genomic characteristics underlying gastric and breast tumorigenesis in this varied population of patients is still unclear. In this review we revised all CDH1 germline mutations described in literature associated with lobular breast cancer (LBC). We distinguish two subgroups of CDH1 mutant carriers: (a) 'mixed' HDGC syndrome, showing both DGC plus LBC and (b) HLBC, in which DGC is absent and the LBC phenotype is predominant. A higher frequency of CDH1 mutations was identified in the HLBC syndrome with an early age at LBC diagnosis; it is possible that LBCs with CDH1 germline mutations are an independent inherited syndrome. This evidence allows us to gain biological insight into the pathophysiological mechanisms responsible for the different phenotypes of the disease and potentially tailor the prophylactic and screening procedures.

The POLO (Partially Omitted Lobe) approach to safely treat in-breast recurrence after intraoperative radiotherapy with electrons.

OBJECTIVES: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC). METHODS: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose. RESULTS: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%. CONCLUSION: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area. ADVANCES IN KNOWLEDGE: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.

Ongoing clinical trials on axillary management.

INTRODUCTION: Within the last 50 years the management of patients with breast cancer has changed dramatically with a significant de-escalation of the role and magnitude of surgery, both for the management of the primary tumor and for the management of the axilla. In the management of the axilla of patients with early stage breast cancer (EBC) and clinically uninvolved axilla (cN0), axillary lymph node dissection (ALND) was gradually replaced by sentinel lymph node biopsy (SLNB) saving more than 60-70% of patients from an unnecessary dissection. Further studies confirmed that isolated tumor cells or micrometastases found on the SLN had no further benefit from ALND sparing even more patients from an unnecessary ALND. Eventually, the Z0011 and other studies showed that even patients with 1-2 positive SLN can be spared from ALND provided they fulfill certain criteria. Still though there were many flaws in these studies and further research was necessary to generalize the results of these studies to a wider target group. Meanwhile, there is a clear view that many low risk patients if they have their axilla evaluated via US and are not found to have suspicious nodes, it is highly unlikely to have involved axilla. This let to studies evaluating the non-surgical management of the axilla. Finally, in the post neoadjuvant setting 3 randomized controlled trials showed that under certain circumstances SLNB can be done after the NAC even in patients who initially had involved axilla and was converted to clinically uninvolved (cN1→cN0). EVIDENCE ACQUISITION: PubMed, Medline, the Cochrane Library Controlled Trials Register as well as National Institutes of Health ClinicalTrials.Gov database have been consulted up to May 2020. EVIDENCE SYNTHESIS: We studied and described the ongoing trials on patients not undergoing neoadjuvant chemotherapy and we discussed the eligibility criteria, the comparison arms and the expected outcomes. We further examined the ongoing trials on patients undergoing neoadjuvant chemotherapy in the same manner. CONCLUSIONS: Although we have covered a long way in the journey of eliminating axillary surgery, there are still lots of questions to be answered and trials to be conducted. We anticipate the results of the ongoing trials to provide the necessary evidence to safely de-escalate more the axillary surgery, both in the non-neoadjuvant as well as in the neoadjuvant setting, hoping that in the not so far future the axillary surgery will eventually perish.

HPV infection and breast cancer. Results of a microarray approach.

OBJECTIVES: Human papilloma virus (HPV) has been implicated in several types of epithelial cancer. The role of HPV in breast carcinogenesis has been a matter of debate fueled by conflicting reports in recent years. The aim of this study is to identify the prevalence of breast and cervical HPV infection in cancer patients by using a modern microarray approach. MATERIALS AND METHODS: In the present prospective study, 201 breast cancer patients were included. For each patient a detailed medical history was taken and during the operation, under sterile conditions, samples were collected, from the tumour, the healthy adjacent breast tissue and any positive sentinel lymph nodes. In addition, for each patient a cervical sample was also collected. All samples were analysed for DNA of 24 types of HPV using a microarray technique. RESULTS: Despite the high sensitivity of the technique used, no HPV DNA was identified in any of the breast or lymph node samples. Our analysis showed that patients with HPV positive cervical samples (28 cases) were more likely to have tumors with positive progesterone receptors (p=0.041) and were also more likely to have two or three positive lymph nodes (p=0.002). CONCLUSION: In the present study, a combination of careful sample collection and a very sensitive microarray approach showed no correlation between HPV and breast cancer. However some characteristics of the breast tumors were different among patients with HPV DNA in their cervical samples.

Laparoscopic versus Open Adrenalectomy for Stage I/II Adrenocortical Carcinoma: Meta-Analysis of Outcomes.

AIM: The aim of the present meta-analysis was to investigate the safety and oncologic efficacy of laparoscopic adrenalectomy for stage I and II adrenocortical carcinoma. The issue of level I evidence is entirely unreturned. METHODS: Electronic databases were used to search for articles from 1992 to 2014 in the English language literature. The primary end point of the study was to evaluate the safety of the laparoscopic procedure in terms of complications and the oncologic effectiveness of the procedure comparing the R0 resection, disease free survival and overall survival of patients treated with open adrenalectomy versus laparoscopic adrenalectomy. RESULTS: Differences in postoperative complications and R0 resections did not reach statistical significance between treatment arms. There were not statistical significant differences between treatment arms considering the two-year, three-year, four-year overall survival while five-year overall survival was in favor of open adrenalectomy group. There were not statistical significant differences between treatment arms considering the two-year, three-year, four-year, and five-year disease free survival. CONCLUSIONS: It seems that postoperative complications, R0-resection, overall, and disease free survival of stage I/II adrenocortical carcinoma are comparable and independent to the procedure though the five-year survival was in favor of the open group. Further research is likely to have an important impact on our confidence in the estimates of effect and may change the estimates.