Influence of nutritional status and body composition on postoperative events and outcome in patients treated for primary localized retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPS) are rare tumours of mesenchymal origin, commonly presented as a large tumour mass at time of diagnosis. We investigated the impact of body composition on outcome in patients operated on for primary localized RPS. PATIENTS AND METHODS: We retrospectively analysed data for all patients operated on for primary RPS at our institution between 1999 and 2020. Preoperative skeletal muscle area (SMA), visceral and subcutaneous adipose tissue area (VAT and SAT) and muscle radiation attenuation (MRA) were calculated using computed tomography scans at the level of third lumbar vertebra. European Working Group on Sarcopenia in Older People (EWGSOP2) criteria were applied to define myopenia. Using maximum log-rank statistic method we determined the optimal cut-off values of body composition parameters. Myosteatosis was defined based on determined MRA cut-offs. RESULTS: In total 58 patient were eligible for the study. With a median follow-up of 116 months, the estimated 5-year overall survival (OS) and local-recurrence free survival (LRFS) were 66.8% and 77.6%, respectively. Patients with myopenia had significantly lower 5-year OS compared to non-myopenic (p = 0.009). Skeletal muscle index and subcutaneous adipose tissue index predicted LRFS on univariate analysis (p = 0.052 and p = 0.039, respectively). In multivariate analysis high visceral-to-subcutaneous adipose tissue area ratio (VSR) independently predicted higher postoperative complication rate (89.2% vs. 10.8%, p = 0.008). Myosteatosis was associated with higher postoperative morbidity. CONCLUSIONS: Myopenia affected survival, but not postoperative outcome in RPS. Visceral obesity, VSR (> 0.26) and myosteatosis were associated with higher postoperative morbidity. VSR was better prognostic factor than VAT in RPS.

Axillary ultrasound for predicting response to neoadjuvant treatment in breast cancer patients-a single institution experience.

BACKGROUND: In node-positive breast cancer patients at diagnosis (cN +) that render node-negative after neoadjuvant systemic treatment (NAST), axillary lymph node dissection (ALND) can be avoided in selected cases. Axillary ultrasound (AUS) is most often used for re-staging after NAST. We aimed to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AUS after NAST for predicting nodal response at the Institute of Oncology, Ljubljana. METHODS: Biopsy-confirmed cN + patients consecutively diagnosed at our institution between 2008 and 2021, who received NAST, followed by surgery were identified retrospectively. Only patients that underwent AUS after NAST were included. AUS results were compared to definite nodal histopathology results. We calculated sensitivity, specificity, PPV and NPV of AUS. We also calculated the proportion of patients with false-positive AUS that results in surgical overtreatment (unnecessary ALND). RESULTS: We identified 437 cN + patients. In 244 (55.8%) AUS after NAST was performed. Among those, 42/244 (17.2%) were triple negative (TN), 78/244 (32.0%) Her-2 positive (Her-2 +), and 124/244 (50,8%) luminal Her-2 negative cancers. AUS was negative in 179/244 (73.4%), suspicious/positive in 65/244 (26.6%) (11/42 (26.2%) TN, 19/78 (24.4%) Her-2 + , and 35/124 (28.2%) luminal Her-2 negative cancers). On definite histopathology, nodal complete response (pCR) was observed in 89/244 (36.5%) (19/42 (45.2%) TN, 55/78 (70.5%) Her-2 + , and 15/124 (12.1%) luminal Her-2 negative cancers). Among patients with suspicious/positive AUS, pCR was observed in 20/65 (30.8%) (6/11 (54.5%) TN, 13/19 (68.4%) Her-2 + and 1/35 (2.9%) luminal Her-2 negative cancers). Sensitivity was 29.0%, specificity 77,5%, PPV 69.2%, NPV 38.5%. Specificity and PPV in TN was 68.4% and 45.4%, in Her-2 + 76.4% and 31.6%, in luminal Her-2 negative 93,3% and 97,1%, respectively. CONCLUSION: In approximately half of the patients, AUS falsely predicts nodal response after NAST and may lead to overtreatment in 30% of the cases (ALND). However, AUS has to be interpreted in context with tumor subtype. In luminal Her-2 negative cancers, it has a high PPV and is therefore useful.

Absence of post-treatment changes in sentinel lymph nodes does not translate into increased regional recurrence rate in initially node-positive breast cancer patients.

PURPOSE: To determine whether the absence of post-treatment changes in the negative sentinel lymph nodes (SLN) in the neoadjuvant setting for biopsy-proven cN + disease results in an increased regional recurrence (RR) rate in patients after SLN biopsy (SLNB) only. METHODS: Breast cancer patients with biopsy-proven cN + disease who converted to node-negative disease after neoadjuvant systemic treatment (NAST) and underwent SLNB only were included. Retrospective analysis was performed for patients diagnosed between 2008 and 2021. Pathohistological specimens were reviewed for the presence of post-treatment changes in the SLNs. Patients with negative SLNs (ypN0) were divided into two groups: (i) with post-treatment changes, (ii) without post-treatment changes. Patients' characteristics were compared between groups. Crude RR rates were compared using the log-rank test. Recurrence-free (RFS) and overall survival (OS) for the entire cohort were calculated using Kaplan-Meier. RESULTS: Of 437 patients with cN + disease, 95 underwent SLNB only. 82 were ypN0, 57 with post-treatment changes (group 1), 25 without post-treatment changes (group 2). During the median follow-up of 37 months (range 6-148), 1 isolated regional recurrence occurred in group 2 (RR rate 0% for group 1 vs. 4% for group 2, p = 0.149). There were no differences in 3-year RFS and OS between groups. CONCLUSION: Absent post-treatment changes in negative SLNs for biopsy-proven cN + disease that covert to node-negative after NAST did not result in increased regional recurrence rates in our cohort. Multidisciplinary input is essential to determine whether additional treatment is needed in these patients.

Variation in response rates to isolated limb perfusion in different soft-tissue tumour subtypes: an international multi-centre study.

OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.

Does concurrent gynaecological surgery affect infectious complications rate after mastectomy with implant-based reconstruction?

BACKGROUND: Women who undergo breast cancer surgery often have an indication for gynaecological procedure. The aim of our study was to compare infectious complications rate after mastectomy with implant-based reconstruction in patients with and without concurrent gynaecological procedure. PATIENTS AND METHODS: We retrospectively reviewed clinical records of 159 consecutively operated patients after mastectomy with implant-based reconstruction. The patients were divided in 2 groups: 102 patients without (Group1) and 57 with (Group 2) concurrent gynaecological procedure. Infectious complications rates between the groups were compared using χ2-test. Logistic regression was performed to test for association of different variables with infectious complications. RESULTS: There were 240 breast reconstructions performed. Median follow-up time was 297 days (10-1061 days). Mean patient age was 47.2 years (95% CI 32.8-65.9); 48.2 years (95% CI 46.1-50.3) in Group 1 and 45.8 years (95% CI 43.2-48.3) in Group 2; p = 0.002). Infectious complications rate was 17.6% (17.6% vs. 17.5%, p = 0.987), implant loss occurred in 5.7% (4.9% vs. 7.0%, p = 0.58). Obesity (body mass index [BMI] > 30 kg/m2), age, previous breast conserving treatment (BCT) with radiotherapy (RT) were identified as risk factors for infectious complications in univariate analysis. Obesity (adjusted odds ratio [aOR] 3.319, 95% CI 1.085-10.157, p = 0.036) and BCT with RT (aOR 7.481, 95% CI 2.230-25.101, p = 0.001) were independently associated with infectious complications in multivariate model. CONCLUSIONS: Concurrent gynaecological procedure for patients undergoing mastectomy with implant-based reconstruction did not carry an increased risk for infectious complications.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Intraoperative Touch Imprint Cytology in Breast Cancer Patients After Neoadjuvant Chemotherapy.

BACKGROUND: Intraoperative touch imprint cytology (ITIC) is used for intraoperative detection of sentinel lymph node (SLN) metastases with intention to spare the patients another surgery. However, ITIC prolongs surgery, and ads costs. It is less likely positive in breast cancer (BC) patients after neoadjuvant chemotherapy (NAC) due to low axillary tumor burden. We aimed to evaluate ITIC in patients after NAC and assess how often it changes the ongoing surgery. MATERIALS AND METHODS: BC patients treated with NAC followed by surgery at the Institute of Oncology Ljubljana, Slovenia, from January 2008 to July 2020 with ITIC performed were selected for analysis. Sensitivity, specificity, and the proportion of positive ITIC were calculated for different subgroups. RESULTS: Overall, 144 patients were identified. 73 of 144 (50.7%) patients were N0 before NAC and 71 of 144 (49.3%) were initially N1 and downstaged to N0 after NAC. ITIC was positive in 30 of 144 (20.8%) of patients, 7 of 73 (9.6%) in N0 group and 23 of 71 (32.4%) in N1 group. In N0 group, ITIC was positive in 1 of 20 (5%) if the tumor size was ≤ 20 mm after NAC, and 2 of 39 (5.1%) if the tumor was triple negative (TN) or Her-2+. In the N1 group ITIC was positive in > 20% in all subgroups. The sensitivity and specificity of ITIC was 50.8% and 100%, respectively and did not differ between groups. CONCLUSION: ITIC after NAC is accurate with comparable sensitivity to ITIC in upfront surgery. We suggest omission of ITIC after NAC in initially N0 patients, particularly for tumors ≤ 20 mm after NAC, and in TN or Her-2+ subtypes.

Sentinel Node Biopsy for Conjunctival Melanoma; Single Centre Experience and Review of Current Literature.

PURPOSE: To evaluate the role of sentinel lymph node (SLN) biopsy in patients with conjuctival melanoma (CjM). STUDY DESIGN: Retrospective observational cohort study and literature review. SUBJECTS: Slovenian patients with CjM are included in the study. METHODS: Prospectively collected data of CjM patients treated from June 2005 to December 2016 were retrospectively analyzed. MAIN OUTCOME MEASURES: The numbers of SLN biopsy procedures, positive and false positive SLN, and local and regional relapses have been described together with overall survival. RESULTS: From June 2005 until December 2016, 24 patients with CjM were treated. The median follow-up time was 65.3 months. The mean Breslow thickness was 1.5 mm (sd = 1.8 mm), and ulceration was present in 29% of cases. Altogether, 14/24 (58%) SLN biopsy procedures were performed. SLN was positive in 2/14 (14%) cases. The estimated 5-year overall survival (OS) of the group was 72.5%, with a median survival of 151 months (95% CI 77-224). From January 2013 to January 2020, five (5/140, 3%) authors reported results comparable to our study. CONCLUSION: Our results confirm that CjM is a rare disease with approximately 14% of positive SLN. At the moment, there are no firm conclusions regarding who would benefit most from SLN biopsy or whether or not CLND should be offered. Data from literature emphasize the need for consistent and uniform staging and future multicentric studies.

Improved Survival after Breast-Conserving Therapy Compared with Mastectomy in Stage I-IIA Breast Cancer.

In the current study, we sought to compare survival outcomes after breast-conserving therapy (BCT) or mastectomy alone in patients with stage I-IIA breast cancer, whose tumors are typically suitable for both locoregional treatments. The study cohort consisted of 1360 patients with stage I-IIA (T1-2N0 or T0-1N1) breast cancer diagnosed between 2001 and 2013 and treated with either BCT (n = 1021, 75.1%) or mastectomy alone (n = 339, 24.9%). Median follow-ups for disease-free survival (DFS) and overall survival (OS) were 6.9 years (range, 0.3-15.9) and 7.5 years (range, 0.2-25.9), respectively. Fifteen (1.1%), 14 (1.0%) and 48 (3.5%) patients experienced local, regional, and distant relapse, respectively. For the whole cohort of patients, the estimated 5-year DFS and OS were 96% and 97%, respectively. After stratification based on the type of local treatment, the estimated 5-year DFS for BCT was 97%, while it was 91% (p < 0.001) for mastectomy-only treatment. Inverse probability of treatment weighting matching based on confounding confirmed that mastectomy was associated with worse DFS (HR 2.839, 95% CI 1.760-4.579, p < 0.0001), but not with OS (HR 1.455, 95% CI 0.844-2.511, p = 0.177). In our study, BCT was shown to have improved disease-specific outcomes compared to mastectomy alone, emphasizing the important role of adjuvant treatments, including postoperative radiation therapy, in patients with early-stage breast cancer at diagnosis.

Reduction of overtreatment without reduction of overdiagnosis in patients with differentiated thyroid cancer: mission impossible.

PURPOSE: Lateral neck nodal metastases are common in patients with differentiated thyroid cancer (DTC) and usually have an indolent nature. They may be detected via neck palpation or preoperative ultrasound (US) of the neck. We hypothesized that preoperative neck metastases detected with US did not affect regional recurrence or long-term survival. METHODS: A retrospective analysis of patients' records treated for DTC at our institution between January 2006 and December 2016 was performed. Information about preoperative US of the neck, treatment, demographics, staging, and histopathology was obtained. The endpoints for the study were nodal recurrence and survival. Differences in survival were analyzed between three groups of patients divided by presence or lack of preoperative US and/or palpable cervical lymph nodes (PLN). Furthermore, the prognostic value of multiple variables was tested by univariate and multivariate analysis. RESULTS: There were 1108 patients with DTC, 221 males and 887 females. The median age was 48.3 years (range 3 to 86), the median time of observation was 68 months (range 0 to 142). Eight hundred sixty-two patients without PLN or preoperative US represented group 1, 112 patients with PLN were in group 2, and 134 patients without PLN and with preoperative US were in group 3. Only five patients had a regional recurrence, one died due to distant metastases. There was no statistically significant difference in survival between the groups (p = 0.841) and neck US was not significantly associated with overall survival neither in univariate nor in multivariate analysis. CONCLUSION: In patients with DTC, the benefits of preoperative US of cervical lymph nodes are probably limited and "less is more" approach is advised.

Trends and timing of risk-reducing mastectomy uptake in unaffected BRCA1 and BRCA2 carriers in Slovenia.

OBJECTIVES: Risk-reducing mastectomy (RRM) is one of key prevention strategies in female carriers of germline BRCA pathogenic/likely pathogenic variants (PV/LPV). We retrospectively investigated the rate, timing and longitudinal trends of bilateral RRM uptake and the incidence and types of cancers among unaffected BRCA carriers who underwent genetic counseling at the Institute of Oncology Ljubljana in Slovenia. MATERIALS AND METHODS: Female BRCA carriers without personal history of cancer were included in the study. Clinical data on PV/LPV type, date of RRM, type of reconstructive procedure, occult carcinoma and histopathology results was collected and analyzed. RESULTS: Of the 346 unaffected BRCA carriers (median age 43 years, 70% BRCA1, 30% BRCA2, median follow-up 46 months) who underwent genetic testing between October 1999 and December 2019, 25.1% had a RRM (range 35-50 years, median age at surgery 38 years). A significant difference in time to prophylactic surgery between women undergoing RRM only vs. women undergoing RRM combined with risk-reducing salpingo-oophorectomy was observed (22.6 vs 8.7 months, p = 0.0009). We observed an upward trend in the annual uptake in line with the previously observed Angelina Jolie effect. In 5.7% of cases, occult breast cancer was detected. No women developed breast cancer after RRM. Women who did not opt for surgical prevention developed BRCA1/2-related cancers (9.3%). CONCLUSION: The uptake of RRM among unaffected BRCA carriers is 25.1% and is similar to our neighboring countries. No women developed breast cancer after RRM while women who did not opt for surgical prevention developed BRCA1/2 related cancers in 9.3% of cases. The reported data may provide meaningful aid for carriers when deciding on an optimal prevention strategy.

Inoperable Primary Retroperitoneal Sarcomas: Clinical Characteristics and Reasons Against Resection at a Single Referral Institution.

BACKGROUND: The outcome of patients with retroperitoneal sarcomas (RPS) depends mainly on tumor biology and completeness of surgical resection. However, some patients are deemed not resectable for various reasons. This study analyzed a series of primary RPS patients to describe rate and reasons of primary inoperability at a large referral center. METHODS: All consecutive patients affected by primary localized RPS referred for surgical treatment at our institution between January 1, 2013 and December 31, 2017 were analyzed. Patients were split in two groups: those who underwent surgical resection with curative intent, and those who were not resected. RESULTS: A total of 322 patients were available for the current analysis: 285 (88.5%) underwent resection with curative intent, and 37 (11.5%) did not. Twenty of 322 (6.2%) patients who did not undergo resection had a technically unresectable tumor, whereas the remaining 18 of 322 (5.6%) were not amenable to a major surgical procedure due to comorbidities/poor performance status. The dominant technical reason was involvement of the celiaco-mesenteric vessels. At a median follow-up from the diagnosis of 34 months, 24 of 37 (64.9%) nonoperated and 48 of 285 (16.8%) operated patients died. The corresponding 4-year overall survival were 10.3% and 83.4%, respectively (p < 0.001). CONCLUSIONS: Roughly, 10% of patients who presented with localized primary RPS at a large referral institution were not resected. An attempt to standardize the definition of resectability for primary localized RPS should be made considering anatomic, biologic, and patient-related factors.

Primary localized retroperitoneal sarcomas: report from Slovenian sarcoma referral center.

BACKGROUND: Sarcoma patients should be treated in high volume referral sarcoma centers. Compartmental resection is proposed as the best treatment option in retroperitoneal sarcoma patients. METHODS: Institute of Oncology Ljubljana is the only referral sarcoma center in Slovenia. Having a population of 2.1 million poses a unique situation. We manage all sarcoma patients in the country and operate on patients with soft tissue tumors of extremities, trunk, and abdomen. Data for all consecutive patients surgically treated from January 1999 to December 2018 for primary localized retroperitoneal sarcoma was extracted from a prospective surgical database. Data about the incidence of sarcoma patients in Slovenia was extracted from the Cancer Registry of Republic of Slovenia. Clinicopathologic variables and the outcome were analyzed. RESULTS: In total, 89 patients were included in the study. Median age was 62 years. Dedifferentiated liposarcoma was the most common histology (38.2%). Median tumor size was 21 cm. Compartmental resection was performed in 47.2% (42/89). Postoperative complication grade 3a or higher according to Clavien-Dindo classification had 30.3% (27/89) of patients. The 30-day and 90-day mortality rate was 2.2% and 5.6%. Median follow-up was 62.1 months. Corresponding 5-year overall survival was 67.2%, 5-year disease-specific survival was 72.6%, and 5-year local recurrence-free survival was 81.5%, respectively. CONCLUSION: Results from our institution show that referral sarcoma centers may achieve very good results in management of retroperitoneal sarcoma patients, despite not meeting the criteria for high volume hospitals, as long as they have multidisciplinary team, appropriate facilities, and expertise.

The prevalence of occult ovarian cancer in the series of 155 consequently operated high risk asymptomatic patients - Slovenian population based study.

Background We assessed the prevalence, localization, type and outcome of occult cancer at risk-reducing salpingo-oophorectomy or salpingectomy (RRSO) in asymptomatic carriers of pathogenic or likely pathogenic BRCA1/2 variants and high-risk BRCA1/2 negative women. Patients and methods A retrospective analysis of all consecutive gynaecologic preventive surgeries from January 2009 to December 2015 was performed. Participants underwent genetic counselling and BRCA1/2 testing before the procedure. Data on clinical parameters, adjuvant treatment and follow-up were collected and analysed. Results One hundred and fifty-five RRSO were performed in 110 BRCA1, 35 BRCA2 carriers of pathogenic or likely pathogenic variants and 10 high-risk BRCA1/2 negative women, at the mean age of 48.3 years. Nine occult cancers (9/155, 5.8%) were identified; eight in BRCA1 positive women and one in high-risk BRCA1/2 negative woman. We identified four non-invasive serous intraepithelial tubal carcinomas (3 in BRCA1 carriers and 1 in a high-risk BRCA1/2 negative woman) and five invasive tubo-ovarian high grade serous cancers (all detected in BRCA1 carriers). Only one out of nine patients (11.1%) with occult cancer had a slightly elevated CA-125 value preoperatively. Conclusions A 5.8% prevalence of occult invasive and noninvasive tubo-ovarian serous cancer after RRSO was found in high risk asymptomatic and screen negative women. We conclude that RRSO should be performed in BRCA1/2 carriers and in high-risk BRCA1/2 negative women. Age of preventive gynaecologic surgery should be carefully planned, taking into account the completion of childbearing age and type of mutation. The results favour the tubal hypothesis of tubal origin of high grade serous ovarian and peritoneal cancer. Cytology result of peritoneal cavity washing was important for the decision making process in determining treatment. Cytology examination should be performed in all cases of RRSO. CA-125 assay did not prove to be an effective screening tool for early cancer detection in our patients.

Does regular quality control improve the quality of surgery in Slovenian breast cancer screening program?

Background The aim of our study was to evaluate the quality of surgery of Slovenian breast cancer screening program (DORA) using the requested EU standards. Furthermore, we investigated whether regular quality control over the 3-year period improved the quality of surgical management. Patients and methods Patients who required surgical management within DORA between January 1st, 2016 and December 31st, 2018 were included in the retrospective study. Quality indicators (QIs) were adjusted mainly according to European Society of Breast Cancer Specialists (EUSOMA) and European Breast Cancer Network (EBCN) recommendations. Five QIs for therapeutic and two for diagnostic surgeries were selected. Additionally, variability in achieving the requested QIs among surgeons was analysed. Results Between 2016 and 2018, 14 surgeons performed 1421 breast procedures in 1398 women. There were 1197 therapeutical (for proven breast cancer) and 224 diagnostic surgical interventions respectively. Overall, the minimal standard was met in two QIs for therapeutic and none for diagnostic procedures. A statistically significant improvement in three QIs for therapeutic and in one QI for diagnostic procedures was observed however, indicating that regular quality control improves the quality of surgery. A high variability in achieving the requested QIs was observed among surgeons, which remained high throughout the study period. Conclusions Adherence to all selected surgical QIs in patients from screening program is difficult to achieve, especially to those specifically defined for screen-detected lesions. Regular quality control may improve results over time. Reducing the number of surgeons dedicated to breast pathology may reduce variability of management inside the institution.

Significance of nuclear factor - kappa beta activation on prostate needle biopsy samples in the evaluation of Gleason score 6 prostatic carcinoma indolence.

Background The goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-κB) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence. Patients and methods Study was conducted on a retrospective cohort of 123 PCa patients with initial total PSA ≤ 10 ng/ml, number of needle biopsy specimens ≥ 8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-κB p65. Both cytoplasmic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease. Results After follow-up of 66 months, biochemical progression (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and nuclear NF-κB p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA ≥ 0.05 ng/ml as cutoff point (p = 0.068). Conclusions Cytoplasmic expression of NF-κB is associated with more biochemical progression and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.

Completely resected stage III melanoma controversy - 15 years of national tertiary centre experience.

BACKGROUND: Two prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients' treatment from Slovenian national CM register to leading international clinical guidelines. PATIENTS AND METHODS: Since 2000, all Slovenian CM patients with primary tumour ≥ TIb are treated at the Institute of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using Kaplan-Meier survival curves and log-rank tests. RESULTS: Positive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs. 47% of metachronous metastases group (MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 45% vs. 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS similar to SLN negative patients (86% vs. 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to the MLNM group (49% vs. 47%; p = 0.280). CONCLUSIONS: Stage III melanoma patients is a heterogeneous group with significant OS differences. CLND after positive SLNB might still remain a method of treatment for selected patients with stage III.

Is preoperative ultrasound of the axilla necessary in screen-detected breast cancer?

BACKGROUND: Axillary ultrasound (US) with fine needle aspiration biopsy (FNAB) of suspicious lymph nodes helps identify patients with axillary metastases preoperatively avoiding a 2-step axillary procedure. However, it does not accurately differentiate between low and high axillary tumour burden. Our aim was to determine the rationale of preoperative axillary US in screen-detected breast cancer. METHODS: We retrospectively analysed patients, aged between 50 and 69 years, which had an invasive breast cancer diagnosed in the Slovenian National Breast Cancer Screening program between January 2012 and June 2017. Proportion of patients that proceeded directly to ALND and the proportion of patients with unnecessary ALND as a result of positive US-FNAB were calculated. RESULTS: Altogether 892 patients were eligible for analysis. Preoperative US of the axilla was performed in 856/892 (96%) patients, while 36/892 patients (4%) did not undergo US of the axilla. We have found out that upfront ALND due to positive US-FNAB was performed in 91/856 (10.6%) patients. 116/856 patients (13.6%) had tumours in inner quadrants and maximal mammographic tumour size ≤ 2 cm. Among them only 1/116 (0.9%) proceeded directly to ALND due to positive US-FNAB.The final pathology of those who underwent upfront ALND due to positive US-FNAB showed low axillary tumour burden not meeting the indications for ALND in 13/91 (14.3%) patients.Among patients without preoperative axillary US, only 1/36 (2.8%) met the indications for ALND. CONCLUSION: Our results showed that performing US of the axilla is not justified in screen detected breast cancer patients.

Genetic Counselling, BRCA1/2 Status and Clinico-pathologic Characteristics of Patients with Ovarian Cancer before 50 Years of Age.

BACKGROUND: In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years. PATIENTS AND METHODS: All clinical data have to be interpreted in the light of many changes happened in the field of EOC just in the last few years: new hystology stage classification (FIGO), new hystology types and differentiation grades classification, new therapeutic possibilities (PARP inhibitors available, also in Slovenia) and new guidelines for genetic counselling of EOC patients (National Comprehensive Cancer Network, NCCN), together with next-generation sequencing possibilities. RESULTS: Compliance rate at the invitation was 43.1%. In the group of 27 invited or previously tested patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4 gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within this extended, partially selected group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected. CONCLUSIONS: The rate of gBRCA1/2 mutation in tested unselected EOC patients under the age of 50 years was higher than 10%, namely 18.5%. Considering also a direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there is a double reason to offer genetic testing to all EOC patients younger than 50 years. Regarding clinical data, it is important to perform their re-interpretation in everyday clinical practice, because this may influence therapeutic possibilities to be offered.

General Overview and Treatment Recommendations for Young Women with Breast Cancer.

Breast cancer in young women is a complex disease to manage due to its biological heterogeneity and special issues related to toxicity of different treatment strategies. Defining a cut-off for young age has been challenging since it is not clear whether the prognostic effect of age is continuously variable or whether there are certain thresholds at which the prognosis changes (e.g. those < 50 years of age or ≤ 35 years of age). In this review article, we define young patients as those being premenopausal. In addition, we discuss the most recent data of the biological diversity of breast cancer arising in premenopausal patients and current treatment modalities in early and advanced settings. Survivorship, with special emphasis on the importance of early supportive care, is also discussed.