Can Morphological and Molecular Parameters of the Primary Breast Tumor Predict the Positivity of Nonsentinel Lymph Nodes After Positive Sentinel Lymph Node Biopsy?

Background: Sentinel lymph node (SLN) biopsy is the gold standard in the evaluation of the axillary status in patients with breast cancer. In cases meeting the Z0011 criteria, no further surgery is needed, while in the remaining cases axillary dissection is required. The aim of the study was to evaluate which morphological and molecular parameters of primary breast tumor or positive SLN can predict the positivity of nonsentinel lymph nodes (NSLN) in order to avoid unnecessary axillary lymphadenectomy. Methods: We conducted a retrospective study on 170 consecutive invasive breast carcinomas, in which SLN biopsy was performed for staging. Results: 42 (24%) cases presented SLN metastases, of which 11 were micrometastases, 6 cases met the Z0011 criteria, requiring no subsequent surgery. 25 patients underwent subsequent ANLD, but only 7 cases (28%) had positive NSLN. In this series, only the tumor diameter 20 mm can predict positive nonsentinel lymph nodes (p= 0.058; CI: 0.05787 to 0.8224). Other parameters such as patient's age (p=0.280; CI:0.7544 to 7.998), histological type (p=0.231; CI: 0.05374 to 9.271), histological grade (p=0.929; CI: 0.2351 to 3.515), molecular profile of the tumor (p=0.362; CI: 0.2416 to 4.663), number of positive SLN (p=0.378; CI: 0.1083 to 1.570), presence of extracapsular extension (p=0.625; CI: 0.5066 to 13.96) and lymph node ratio (p=0.656; CI: 0.5068 to 5.768) cannot predict the presence of metastasis in the NSLN. Conclusion: In cases in which the patient does not meet the Z0011 criteria and/or these criteria are not used, axillary lymph node dissection is the surgical treatment of choice.

The Accuracy of the Preoperative Axillary Ultrasound Examination in Predicting the Status of the Sentinel Lymph Node Involvement in Patients with Infiltrating Breast Carcinoma.

Background: we aimed to determine the accuracy of preoperative axillary ultrasound (US) in predicting the presence of sentinel lymph node (SLN) metastasis in breast cancer patients. Methods and Results: out of 54 cases, visible nodes on US were identified in 35 cases of which, 15 had metastasis. In 19 cases no axillary lymph nodes were visible on US. Of these, only 3 had metastasis. Moreover, our results demonstrated that neither the maximum diameter (p=0.738 Fisher exact test) nor the ratio between the longitudinal and transverse axes (p=0.728 Fisher exact test) can predict the positivity of the SLN. Conclusion: US cannot predict the positivity of the SLN.

Clinical Outcomes of HPV-associated and Unassociated Endocervical Adenocarcinomas Categorized by the International Endocervical Adenocarcinoma Criteria and Classification (IECC).

The International Endocervical Adenocarcinoma Criteria and Classification (IECC) categorizes endocervical adenocarcinomas (ECAs) on the basis of morphologic features linked to etiology (ie, human papilloma virus [HPV] infection), resulting in separation of ECAs into HPV-associated (HPVA) and unassociated or non-HPVA (NHPVA) types. NHPVAs are reported to be large and present at high stage in older individuals. Our aim was to examine the clinical outcomes in these tumor types. Full slide sets of 205 ECAs were collected from 7 institutions worldwide and classified on the basis of IECC criteria and the presence or absence of HPV. Clinical and morphologic parameters were correlated with follow-up data. Statistical analysis of overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were conducted using the Kaplan-Meier survival analysis and compared using the log-rank test for univariate analysis. Multivariate survival analysis was conducted, and the survival endpoints considered were OS, DFS, and PFS. Statistically significant survival differences (OS, DFS, and PFS) were found when comparing the following categories: HPVA>NHPVA (ie, survival was superior in the setting of HPVAs), including patients treated with surgery followed by adjuvant therapy; usual-type HPVA>mucinous HPVA; FIGO grade 3 HPVA>NHPVA; HPVA>NHPVA, both with lymphovascular invasion; and HPVA>NHPVA in patients with pelvic recurrences. Although there were trends favoring HPVA outcomes over those of NHPVA, these differences were not statistically significant in the following categories: mucinous HPVA versus NHPVA; HPVA versus NHPVA, both with lymph node metastases at presentation; and HPVA versus NHPVA in patients with distant metastasis. Survival for both HPVA and NHPVA was similar when surgery without adjuvant therapy was used. FIGO grading did not have prognostic significance in HPVAs. Multivariable analysis of HPVAs indicated nearly significant statistical associations between stage and both OS and DFS (P=0.07 and 0.06, respectively), and between Silva invasion pattern and OS (P=0.09). Multivariate analysis of NHPVAs indicated a statistically significant association between OS and age (P=0.03), stage (P=0.02) and tumor size (P=0.002), and between DFS and stage (P=0.004) and tumor size (P=0.004). Multivariate analysis of HPVAs and NHPVAs together revealed nearly significant associations between OS and HPV status and stage (both [P=0.06]). For DFS, stage was a significant variable (P=0.04), whereas HPV status and tumor size were nearly significant (P=0.06 and 0.07, respectively). Clinical outcome studies support the idea that the IECC classification not only separates ECAs on the basis of HPV status (usually assessed on H&E slides), but also has important clinical relevance.

Cervical adenosquamous carcinoma: detailed analysis of morphology, immunohistochemical profile, and clinical outcomes in 59 cases.

Although 2014 World Health Organization criteria require unequivocal glandular and squamous differentiation for a diagnosis of cervical adenosquamous carcinoma, in practice, adenosquamous carcinoma diagnoses are often made in tumors that lack unequivocal squamous and/or glandular differentiation. Considering the ambiguous etiologic, morphological, and clinical features and outcomes associated with adenosquamous carcinomas, we sought to redefine these tumors. We reviewed slides from 59 initially diagnosed adenosquamous carcinomas (including glassy cell carcinoma and related lesions) to confirm an adenosquamous carcinoma diagnosis only in the presence of unequivocal malignant glandular and squamous differentiation. Select cases underwent immunohistochemical profiling as well as human papillomavirus (HPV) testing by in situ hybridization. Of the 59 cases originally classified as adenosquamous carcinomas, 34 retained their adenosquamous carcinoma diagnosis, 9 were reclassified as pure invasive stratified mucin-producing carcinomas, 10 as invasive stratified mucin-producing carcinomas with other components (such as HPV-associated mucinous, usual-type, or adenosquamous carcinomas), and 4 as HPV-associated usual or mucinous adenocarcinomas with benign-appearing squamous metaplasia. Two glassy cell carcinomas were reclassified as poorly differentiated usual-type carcinomas based on morphology and immunophenotype. There were significant immunophenotypic differences between adenosquamous carcinomas and pure invasive stratified mucin-producing carcinomas with regard to HPV (p < 0.0001), PAX8 (p = 0.038; more in adenosquamous carcinoma), p40 (p < 0.0001; more in adenosquamous carcinoma), p63 (p = 0.0018; more in adenosquamous carcinoma) and MUC6 (p < 0.0001; less in adenosquamous carcinoma), HNF-1beta (p = 0.0023), vimentin (p = 0.0003), p53 (p = 0.0004), and CK7 (p = 0.0002) expression. Survival outcomes were similar between all groups. Adenosquamous carcinomas should be diagnosed only in the presence of unequivocal malignant glandular and squamous differentiation. The two putative glassy cell carcinomas studied did not meet our criteria for adenosquamous carcinoma, and categorizing them as such should be reconsidered.

Obtaining adequate surgical margin status in breast-conservation therapy: intraoperative ultrasound-guided resection versus specimen mammography.

BACKGROUND AND AIM: The purpose of breast-conserving surgery (BCS) for women with cancer is to perform an oncological radical procedure with disease-free margins at the final histological assessment and with the best aesthetic result possible. Intraoperative resected specimen ultrasound and intraoperative resected specimen mammography may reduce the rates of positive margins and reexcision among patients undergoing conserving therapy. Our objective is to compare the two methods with the histopathological results for a preset cut off and asses which parameters can influence the positive margin status. METHOD: A prospective study was performed on 83 patients who underwent breast conservation surgery for early breast cancer (pT1-3a pN0-1 M0) between 2014 and 2016. After excision the specimen was oriented in the operating room by the surgeon. Metallic clips and threads were placed on margins: one clip and the long thread at 12 o'clock, two clips and the short threads at 9 o'clock. The next step was intraoperative ultrasound assessment of the specimen. For the margins under 2 mm we performed selective margin shaving, followed by mammography to identify and document the lesion and finally histopathological examination of the specimen with reporting the gross and microscopic margins. The positive margins required re-excision or boost of radiation at the posterior or anterior margins, depending on the case. RESULTS: We set a cut-off at 2 mm. The sensitivity and specificity of the intraoperative margin assessment via the ultrasound method were 90.91% (95% CI 70.84-98.88%) and 67.21% (95% CI 54-78.69%) respectively. The sensitivity and specificity of the intraoperative margin assessment via the mammographic procedure were 45.45% (95% CI 24.39-67.79%) and 85.25% (95% CI 73.83-93.02%) respectively. There was positive correlation between the histopathological and intraoperative ultrasound exam (p=0.018) and negative correlation between the histopathological exam and the post-operative mammographic exam (p=0.68). We found a positive correlation between the positive margin status and age (<40), preoperative chemotherapy, intraductal carcinoma, inflammatory process around the tumor, and the immunohistochemical triple negative profile. CONCLUSIONS: According to our results, the intraoperative ultrasound of the breast specimen for a cutt-off at 2 mm can decrease the rates of margin positivity compared to the mammographic procedure and has the potential to diminish the number of subsequent undesired re-excisions.

The Revisited Role of Ultrasound Guided Core Needle Biopsy in the Breast Cancer Diagnosis.

Background: Core needle biopsy (CNB) is an alternative to surgical biopsy in establishing the histopathological diagnosis of mammary lesions. AIM OF THE STUDY: The aim is to determine the accuracy of ultrasound guided CNB (US-CNB) in establishing breast cancer diagnosis. MATERIALS AND METHODS: We retrospectively analyzed the data of US-CNB patients between May 2012 - December 2014. One hundred sixty-three biopsies were performed in 155 patients. To assess the diagnostic accuracy of US-CNB, the results were correlated with the gold-standard of surgical excision of the breast lesions, thus, 90 patients (94 breast lesions) were included in the study group. We calculated the concordance of the results using the Kappa Coefficient, sensitivity and specificity using the ROC curve and the false-negative rate. Results: US-CNB identified 74 (79%) malignant lesions, 1 (1%) precursor high-risk lesion, and 19 (20%) benign lesions. Concordance between histopathological results was 96.8% (kappa: 0.91). The 94.2% (kappa: 0.80) consensus of the histological type could be calculated for 70 invasive carcinomas. The 61.8% (kappa: 0.41) concordance of the histological grade could be calculated for 55 invasive carcinomas. Sensitivity and specificity were 98.6%, and 100%, respectively. The false-negative rate was 1.3%. Conclusions: US-CNB is an excellent alternative to surgical biopsy in establishing the histopathological diagnosis of breast lesions, provided it is performed by a specialized team and there is clinical-radiological-histopathological concordance in all cases.

[Experimental study on the resistance to intraluminal pressure between handsewn and stapled anastomosis. In vitro experimental study]. / A bélrendszer kézi és gépi anastomosisainak nyomással szembeni ellenálló képességének felmérése. In vitro kísérletes tanulmány.

Intoduction and aim: The aim of the study was to compare the resistance to pressure of stapled and manually handsewn intestinal suture lines on in vitro pig intestine model. METHOD: We performed different types of stapled and manual sutures and the pressure level was measured using a differential pressure manometer. RESULTS: Although the hand-sewn end-to-end suture turned out to be the most resistant to pressure, statistical analysis revealed no significant differences compared to stapled suture (p = 0.49). In stump closure techniques, we observed a statistically high significance in resistance to pressure in the favour of manual stump closure (p = 0.004).Regarding side-to-side sutures we did not find any statistically significant differences in resistance to pressure between the techniques (p = 0.06). CONCLUSION: We can conclude that regarding the stump closure, the most resistant to pressure is the hand-sewn procedure, but in the other types of anastomosis, no significant differences was found between the stapled and hand-sewn techniques. Orv Hetil. 2017; 158(42): 1674-1680.

Correlation between obesity and prognostic/predictive parameters with emphasis on the importance of lymph node metastases in patients with invasive breast carcinoma.

We aimed to evaluate whether obese women experience more advanced invasive breast carcinoma (IBC) with a higher number of involved lymph nodes, higher range of axillary lymph node ratio (LNR) and presence and size of extracapsular extension as it may have an impact on prognosis and management. 245 patients diagnosed with IBC were divided into normal weight (NW), overweight (OW) and obese (OB) groups. Patients were divided into high range of LNR (LNR over or equal to 0.2) and low LNR (LNR less than 0.2). The extracapsular extension dimensions were measured on the original slides of each case and grouped into ≤ 1 mm and > 1 mm. 84 patients (33.07%) were OW, 72 (29.38%) OB and 91 (37.14%) NW. 45.7% of cases had macrometastasis in the axillary lymph nodes. NW patients had significantly fewer metastatic lymph nodes (p = 0.05) than in the OW/OB groups. There was no statistically significant difference between BMI groups according to the LNR (p = 0.66). Out of 111 cases with macrometastasis, 58 cases (52.25%) had extracapsular extension (ECE) (11.7% NW, 24.32% OW and 16.22% OB). Significantly more OW patients presented extranodal invasion (p = 0.04). We found no statistically significant relationship between the extracapsular extension diameter and BMI groups (p = 0.1).