Salvatore Vieni

Secretory breast carcinoma with metastatic sentinel lymph node

BackgroundSecretory mammary carcinoma is a rare breast neoplasia originally described in children but sometimes also found in adults. It presents a more favourable outcome than more common histological types of breast carcinoma; published literature in fact reports only a few cases with axillary lymph node metastases and only four cases with distant metastases.Clinical presentationIn this paper we report a rare case of secretory breast carcinoma with axillary lymph node metastases in a 33-year-old woman. To our knowledge, this is the first case of secretory carcinoma involving biopsy of the sentinel lymph node and investigation of the e-cadherin expression.We found positivity for e-cadherin, which would support the hypothesis that this type of tumour is a variant of the infiltrating ductal carcinoma.ConclusionAfter a careful analysis of reported data, we have come to the conclusion that the treatment of choice for patients with secretory breast carcinoma should be conservative surgery with sentinel lymph node biopsy, followed by accurate follow-up. We are of the opinion that while post-operative radiotherapy is indicated in adult patients who have undergone quadrantectomy, it should not be used in children. Although several cases of secretory carcinoma have been treated with adjuvant chemotherapy, there are still no reliable data regarding the real value of such a choice.

Does the use of fibrin glue prevent seroma formation after axillary lymphadenectomy for breast cancer? A prospective randomized trial in 159 patients.

Seroma formation frequently occurs in patients who have undergone axillary lymphadenectomy. The aim of the study was to evaluate the effect of fibrin glue in the prevention of seroma formation after axillary lymphadenectomy.

LigaSure in total thyroidectomy

PurposeLigaSure is a bipolar diathermy system, which achieves vessel sealing with reduced thermal spread. The device has been used successfully in abdominal operations and because of its features, it has been applied recently in thyroid surgery to minimize the risk of complications such as laryngeal nerve palsy and hypocalcemia, and also to reduce the operating time.MethodsBetween June and December 2005, we performed total thyroidectomy for various disorders in 105 patients. We used the LigaSure diathermy system in 53 patients and traditional hemostatic procedures in the other 52. We evaluated the demographic features, histopathological diagnosis, operating times, and relevant postoperative complications.ResultsThe two study groups had similar demographic and histopathological features. The mean operating time ± SD was not significantly shorter in the LigaSure group than in the traditional group (104 ± 12.7 vs 110 ± 15.6 min). None of the patients in either group suffered hemorrhage, definitive hypocalcemia, or definitive laryngeal nerve palsy. Transient hypocalcemia and transient laryngeal nerve palsy developed in 7.54% and in 1.88%, respectively, of the patients in the LigaSure group, and in 7.69% and 1.92%, respectively, of the patients in the traditional group; these differences were not significant.ConclusionsLigaSure is a safe and effective method of hemostasis control, but it did not reduce the incidence of complications or operating times compared with traditional hemostatic procedures; moreover, the operative costs were higher.

The value of intraoperative frozen section examination of sentinel lymph nodes in surgical management of breast carcinoma

PurposeIn breast cancer staging, the need for intraoperative sentinel lymph node (SLN) evaluation has still not been adequately established. This study investigates the impact of intraoperative frozen section (FS) evaluation of SLN to avoid subsequent axillary lymph node dissection (ALND) in patients with positive SLN.MethodsA retrospective review of 364 breast cancer patients undergoing SLN biopsy with intraoperative FS evaluation of SLN was performed.ResultsSensitivity and accuracy of FS examination of SLN were 76.4% and 94.2%, respectively. The sensitivity was significantly higher in larger tumors (p < 0.01). No significant correlation was found between FS and histologic type. A second intervention was avoided in 83.9% of the patients with positive SLN.ConclusionsIntraoperative FS examination of the SLN is a useful predictor of axillary lymph node status in breast cancer patients. The majority of SLN-positive patients allows for immediate ALND in a one-stage surgical procedure.

TP53 Mutations and S-Phase Fraction but not DNA-Ploidy Are Independent Prognostic Indicators in Laryngeal Squamous Cell Carcinoma

To prospectively evaluate the prognostic significance of TP53, H‐, K‐, and N‐Ras mutations, DNA‐ploidy and S‐phase fraction (SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight‐one patients (median follow‐up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA‐ploidy and SPF were performed by flow cytometric analyses. Thirty‐six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triple mutations. In total, 46 TP53 mutations were observed. The majority (41%) of these occur in exon 5 (19/46), while the mutations in exons 6, 7, and 8 were represented in 14, 7, and 6 patients, respectively (31%, 15%, and 16%). Five LSCC patients (6%) showed a mutation in H‐Ras gene. Sixty‐three percent of the cases (51/81) were DNA aneuploidy, 14% of these (7/51) were multiclonal. Thirty‐nine patients (48%) had an high SPF value. At Univariate analysis, the DNA aneuploidy, high SPF (>15.1%), TP53 mutations and, in particular, the mutations that occur in exons 5 and 8 were significantly related to quicker disease relapse and short OS. At Multivariate analysis, the major significant predictors for both disease relapse and death were high SPF and any TP53 mutations. While histological grade G3 was an independent factor only for relapse. In conclusions, any TP53 mutations and high SPF are important biological indicators to predict the outcome of LSCC patients.

ΔNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis

P63 is a transcription factor belonging to the family of p53, essential for the development and differentiation of epithelia. In recent years, it has become clear that altered expression of the different isoforms of this gene can play an important role in carcinogenesis. The p63 gene encodes for two main isoforms known as TA and ΔN p63 with different functions. The role of these different isoforms in sustaining tumor progression and metastatic spreading however has not entirely been clarified. Here we show that breast cancer initiating cells express ΔNp63 isoform that supports a more mesenchymal phenotype associated with a higher tumorigenic and metastatic potential. On the contrary, the majority of cells within the tumor appears to express predominantly TAp63 isoform. While ΔNp63 exerts its effects by regulating a PI3K/CD44v6 pathway, TAp63 modulates this pathway in an opposite fashion. As a result, tumorigenicity and invasive capacity of breast cancer cells is a balance of the two isoforms. Finally, we found that tumor microenvironmental cytokines significantly contribute to the establishment of breast cancer cell phenotype by positively regulating ΔNp63 and CD44v6 expression.

Dietary restriction: could it be considered as speed bump on tumor progression road?

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or molecular mechanism underlying the benefits to the different dietary approaches. It is well known that the healthy effect is mediated in part by the reduction of nutrient-related pathways. The calorie restriction and starvation (long- and short-term) also suppress the inflammatory response reducing the expression, for example, of IL-10 and TNF-α, mitigating pro-inflammatory gene expression and increasing anti-inflammatory gene expression. The dietary restriction may regulate both genes involved in cellular proliferation and factors associated to apoptosis in normal and cancer cells. Finally, dietary restriction is an important tool that may influence the response to chemotherapy in preclinical models. However, further data are needed to correlate dietary approaches with chemotherapeutic treatments in human models. The aim of this review is to discuss the effects of various dietary approaches on the cancer progression and therapy response, mainly in preclinical models, describing some signaling pathways involved in these processes.

Distinctive features of tumor-infiltrating gd T lymphocytes in human colorectal cancer

ABSTRACT γδ T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating γδ T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of γδ T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5–90%) and 4% γδ T cells on average, with the majority expressing Vδ1. Most Vδ1 and Vδ2 T cells showed a predominant effector memory phenotype and had reduced production of IFN- γ which was likely due to yet unidentified inhibitory molecules present in cancer stem cell secretome. Transcriptome analyses revealed that patients containing abundant γδ T cells had significantly longer 5-year disease free survival rate, suggesting their efficacy in controlling tumor at very early stage.

IL4 Primes the Dynamics of Breast Cancer Progression via DUSP4 Inhibition

The tumor microenvironment supplies proinflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL4 secreted by adipose tissue and estrogen receptor-positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL4 signaling with the IL4Rα antagonist IL4DM compromised breast cancer cell proliferation, invasion, and tumor growth by downregulating MAPK pathway activity. IL4DM reduced numbers of CD44+/CD24- cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-κB. Enforced expression of DUSP4 drove conversion of metastatic cells to nonmetastatic cells. Mechanistically, RNAi-mediated attenuation of DUSP4 activated the ERK and p38 MAPK pathways, increased stem-like properties, and spawned metastatic capacity. Targeting IL4 signaling sensitized breast cancer cells to anticancer therapy and strengthened immune responses by enhancing the number of IFNγ-positive CTLs. Our results showed the role of IL4 in promoting breast cancer aggressiveness and how its targeting may improve the efficacy of current therapies. Cancer Res; 77(12); 3268-79. ©2017 AACR.

Clinical presentation and treatment of gastrointestinal stromal tumors.

Aims and background Gastrointestinal stromal tumors (GISTs), although rare, are the most common mesenchymal neoplasms affecting the gastrointestinal tract. We present our experience in the treatment of localized and metastatic disease and a review of literature. Patients and methods Nine patients were observed from April 2002 to July 2004. Eight tumors were in the gastric area and J was in the small bowel. In 5 cases, complete surgical removal was performed, and none of these patients underwent adjuvant therapy. The remaining 4 cases, with locally advanced or recurrent disease, were treated with imatinib. Results The patients with localized disease treated only by surgery did not relapse. In the patients with locally advanced or metastatic disease treated by imatinib, we observed 3 partial responses, and one case was not assessable because he had no measurable disease. In 2 of 3 responders, it was possible to perform a new radical surgery. Conclusions Our series is too small to draw any conclusion. According to our review of the literature, surgery remains the standard treatment for non-metastatic GISTs. Imatinib mesylate represents a major breakthrough in the treatment of advanced GISTs and is the first effective systemic therapy for the disease.