Axillary Surgery for Breast Cancer in 2024.

Axillary surgery for patients with breast cancer (BC) in 2024 is becoming increasingly specific, moving away from the previous 'one size fits all' radical approach. The goal is to spare morbidity whilst maintaining oncologic safety. In the upfront surgery setting, a first landmark randomized controlled trial (RCT) on the omission of any surgical axillary staging in patients with unremarkable clinical examination and axillary ultrasound showed non-inferiority to sentinel lymph node (SLN) biopsy (SLNB). The study population consisted of 87.8% postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative BC. Patients with clinically node-negative breast cancer and up to two positive SLNs can safely be spared axillary dissection (ALND) even in the context of mastectomy or extranodal extension. In patients enrolled in the TAXIS trial, adjuvant systemic treatment was shown to be similar with or without ALND despite the loss of staging information. After neoadjuvant chemotherapy (NACT), targeted lymph node removal with or without SLNB showed a lower false-negative rate to determine nodal pathological complete response (pCR) compared to SLNB alone. However, oncologic outcomes do not appear to differ in patients with nodal pCR determined by either one of the two concepts, according to a recently published global, retrospective, real-world study. Real-world studies generally have a lower level of evidence than RCTs, but they are feasible quickly and with a large sample size. Another global real-world study provides evidence that even patients with residual isolated tumor cells can be safely spared from ALND. In general, few indications for ALND remain. Three randomized controlled trials are ongoing for patients with clinically node-positive BC in the upfront surgery setting and residual disease after NACT. Pending the results of these trials, ALND remains indicated in these patients.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Impact of Imaging-Guided Localization on Performance of Tailored Axillary Surgery in Patients with Clinically Node-Positive Breast Cancer: Prospective Cohort Study Within TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

BACKGROUND: Tailored axillary surgery (TAS) is a novel surgical concept for clinical node-positive breast cancer. It consists of the removal of the sentinel lymph nodes (LNs), as well as palpably suspicious nodes. The TAS technique can be utilized in both the upfront and neoadjuvant chemotherapy (NACT) setting. This study assessed whether/how imaging-guided localization (IGL) influenced TAS. PATIENTS AND METHODS: This was a prospective observational cohort study preplanned in the randomized phase-III OPBC-03/TAXIS trial. IGL was performed at the surgeon's discretion for targeted removal of LNs during TAS. Immediate back-up axillary lymph node dissection (ALND) followed TAS according to TAXIS randomization. RESULTS: Five-hundred patients were included from 44 breast centers in six countries, 151 (30.2%) of whom underwent NACT. IGL was performed in 84.4% of all patients, with significant variation by country (77.6-100%, p < 0.001). No difference in the median number of removed (5 vs. 4, p = 0.3) and positive (2 vs. 2, p = 0.6) LNs by use of IGL was noted. The number of LNs removed during TAS with IGL remained stable over time (p = 0.8), but decreased significantly without IGL, from six (IQR 4-6) in 2019 to four (IQR 3-4) in 2022 (p = 0.015). An ALND was performed in 249 patients, removing another 12 (IQR 9-17) LNs, in which a median number of 1 (IQR 0-4) was positive. There was no significant difference in residual nodal disease after TAS with or without IGL (68.0% vs. 57.6%, p = 0.2). CONCLUSIONS: IGL did not significantly change either the performance of TAS or the volume of residual nodal tumor burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03513614.

The American Society of Breast Surgeons classification system for oncoplastic breast conserving surgery independently predicts the risk of delayed wound healing.

INTRODUCTION: Oncoplastic breast conserving surgery (OBCS) aims to provide safe and satisfying surgery for breast cancer patients. The American Society of Breast Surgeons (ASBrS) classification system is based on volumetric displacement cut-offs (level I for <20% of breast volume; level II for 20-50%). It aims to facilitate communication among treating physicians and patients. Here, we investigate whether the extent of OBCS as classified by ASBrS independently predicts postoperative complications. MATERIALS AND METHODS: This retrospective analysis of a prospectively maintained database included patients with stage I-III breast cancer who underwent OBCS between 03/2011 and 12/2020 at a Swiss university hospital. Outcomes included short-term (≤30 days) complications and chronic (>30 days) pain after surgery. Multivariate logistic regression models were used to identify independent predictors. RESULTS: In total, 439 patients were included, 314 (71.5%) received ASBrS level I surgery, and 125 (28.5%) underwent ASBrS level II surgery. ASBrS level II was found to be an independent predictor of delayed wound healing (odds ratio [OR] 9.75, 95% confidence intervals (CI) 2.96-32.10). However, ASBrS level did not predict chronic postoperative pain (incidence rate ratio [IRR] 1.20, 95%CI 0.85-1.70), as opposed to age (IRR 1.19, 95%CI 1.11-1.27 per 5 years decrease), and weight disorders (underweight [BMI <18.5] vs. normal weight [BMI 18.5 < 25]: IRR 4.02, 95%CI 1.70-9.54; obese [BMI ≥30] vs. normal weight: IRR 2.07, 95%CI 1.37-3.13). CONCLUSION: ASBrS level II surgery predicted delayed wound healing, warranting close clinical follow-up and prompt treatment to avoid delays in adjuvant therapy.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Use of sentinel lymph node biopsy in elderly patients with breast cancer - 10-year experience from a Swiss university hospital.

BACKGROUND: The Choosing Wisely initiative recommended the omission of routine sentinel lymph node biopsy (SLNB) in patients ≥ 70 years of age, with clinically node-negative, early stage, hormone receptor (HR) positive and human epidermal growth factor receptor 2 (Her2) negative breast cancer in August 2016. Here, we assess the adherence to this recommendation in a Swiss university hospital. METHODS: We conducted a retrospective single center cohort study from a prospectively maintained database. Patients ≥ 18 years of age with node-negative breast cancer were treated between 05/2011 and 03/2022. The primary outcome was the percentage of patients in the Choosing Wisely target group who underwent SLNB before and after the initiative went live. Statistical significance was tested using chi-squared test for categorical and Wilcoxon rank-sum tests for continuous variables. RESULTS: In total, 586 patients met the inclusion criteria with a median follow-up of 2.7 years. Of these, 163 were ≥ 70 years of age and 79 were eligible for treatment according to the Choosing Wisely recommendations. There was a trend toward a higher rate of SLNB (92.7% vs. 75.0%, p = 0.07) after the Choosing Wisely recommendations were published. In patients ≥ 70 years with invasive disease, fewer received adjuvant radiotherapy after omission of SLNB (6.2% vs. 64.0%, p < 0.001), without differences concerning adjuvant systemic therapy. Both short-term and long-term complication rates after SLNB were low, without differences between elderly patients and those < 70 years. CONCLUSIONS: Choosing Wisely recommendations did not result in a decreased use of SLNB in the elderly at a Swiss university hospital.

Trends in use of neoadjuvant systemic therapy in patients with clinically node-positive breast cancer in Europe: prospective TAXIS study (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

PURPOSE: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe. METHODS: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery. The TAXIS study's pragmatic design allowed both the neoadjuvant and adjuvant setting according to the preferences of the local investigators who were encouraged to register eligible patients consecutively. RESULTS: A total of 500 patients were included at 44 breast centers in six European countries from August 2018 to June 2022, 165 (33%) of whom underwent NST. Median age was 57 years (interquartile range [IQR], 48-69). Most patients were postmenopausal (68.4%) with grade 2 and 3 hormonal receptor-positive and human epidermal growth factor receptor 2-negative breast cancer with a median tumor size of 28 mm (IQR 20-40). The use of NST varied significantly across the countries (p < 0.001). Austria (55.2%) and Switzerland (35.8%) had the highest percentage of patients undergoing NST and Hungary (18.2%) the lowest. The administration of NST increased significantly over the years (OR 1.42; p < 0.001) and more than doubled from 20 to 46.7% between 2018 and 2022. CONCLUSION: Substantial heterogeneity in the use of NST with HR+/HER2-breast cancer exists in Europe. While stringent guidelines are available for its use in triple-negative and HER2+ breast cancer, there is a need for the development of and adherence to well-defined recommendations for HR+/HER2-breast cancer.

Therapeutic approaches in patients with bone metastasis due to endometrial carcinoma - A systematic review.

Background: Bone metastases (BM) are uncommon in endometrial carcinoma (EC), without information on the optimal oncologic management of patients with BM in EC. Here, we systematically review clinical characteristics, treatment approaches and prognosis in patients with BM in EC. Methods: We conducted a systematic literature search until 27th March 2022 on PubMed, MEDLINE, Embase and clinicaltrials.gov. Outcomes included treatment frequency and survival after BM with comparators being treatment approaches (local cytoreductive bone surgery, systemic therapy, and local radiotherapy). Risk of bias was assessed using the NIH Quality Assessment Tool and Navigation Guide methodology. Results: We retrieved 1096 records of which 112 retrospective studies (12 cohort studies, 12/12 fair quality; 100 case studies, 100/100 low quality) with a total of 1566 patients were included. The majority had a primary diagnosis of FIGO stage IV, grade 3 endometrioid EC. Singular BM were present in a median of 39.2%, multiple BM in 60.8% and synchronous additional distant metastases in 48.1% of patients respectively. In patients with secondary BM median time to bone recurrence was 14 months. Median survival after BM was 12 months. Local cytoreductive bone surgery was assessed in 7/13 cohorts and performed in a median of 15.8% (interquartile range [IQR] 10.3-43.0) of patients. Chemotherapy was assessed in 11/13 cohorts and administered in a median of 55.5% (IQR 41.0-63.9), hormonal therapy (7/13 cohorts) in 24.7% (IQR 16.3-36.0), and osteooncologic therapy (4/13 cohorts) in 2.7% (IQR 0.0-7.5) of patients respectively. Local radiotherapy was assessed in 9/13 cohorts and performed in a median of 66.7% (IQR 55.6-70.0) of patients. Survival benefits were seen in 2/3 cohorts after local cytoreductive bone surgery, and in 2/7 cohorts after chemotherapy without survival benefits in the remaining cohorts and investigated therapies. Limitations include the lack of controlled intervention studies, the heterogeneity and retrospective nature of the investigated populations. Conclusions: This systematic review shows heterogenous therapeutic approaches in clinical practice without clear evidence for optimal oncologic management for patients with BM in EC.

Uncertainties and controversies in axillary management of patients with breast cancer.

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.

Tailored axillary surgery - A novel concept for clinically node positive breast cancer.

Axillary surgery in patients with breast cancer has been a history of de-escalation; however, surgery for clinically node-positive breast cancer remained at the dogmatic level of axillary lymph node dissection (ALND). In these patients, currently the only way to avoid ALND is neoadjuvant systemic treatment (NST) with nodal pathologic complete response (pCR) as diagnosed by selective lymph node removal. However, pCR rates are highly dependent on tumor biology, with luminal tumors being most present yet showing the lowest pCR rates. Therefore, the TAXIS trial is investigating whether in clinically node-positive patients, either with residual disease after NST or in the upfront surgical setting, ALND can be safely omitted. All patients undergo tailored axillary surgery (TAS), which includes removal of the biopsied and clipped node, the sentinel lymph nodes as well as all palpably suspicious nodes, turning a clinically positive axilla into a clinically negative. Feasibility of TAS was recently confirmed in the first pre-specified TAXIS substudy. TAS is followed by axillary radiotherapy to treat any remaining nodal disease. Disease-free survival is the primary endpoint of this non-inferiority trial, and morbidity as well as quality of life are the main secondary endpoints, with ALND being known for having a relevant negative impact on both. Currently, 663 of 1500 patients were randomized; accrual completion is projected for 2025. The TAXIS trial stands out in including clinically node-positive patients in both the neoadjuvant and upfront surgery setting, thereby investigating surgical de-escalation at the far-end of the risk spectrum of patients with breast cancer.

Hospitalization rates, stroke unit care, and recurrence rates in Austria's stroke cohort Epidemiologic analysis of 102,107 patients in a nation-wide acute stroke cohort between 2015 and 2019.

Introduction: Continuous analysis of key epidemiologic data is irremissible to adapt health-care systems to trends in stroke epidemiology. We present data from 2015 to 2019 on quality indicators of stroke care, including rates on hospitalization, stroke unit care and recurrence rates using medical record-linkage of in-patient routine documentation. Patients and methods: We included stroke/TIA patients admitted to Austrian hospitals between 2015 and 2019 aged ⩾20 years using medical record-linkage. Results: In our cohort of 102,107 patients with 107,055 treatment episodes, we could show a significant decrease in 1-year cumulative age-adjusted hospitalization rates per 100,000 in TIA (86.3 [95% CI 84.1-88.5] vs 75.4 [95% CI 73.4-77.4], RR 0.87 [95% CI 0.85-0.90]), ischemic stroke (187.3 [95% CI 184.0-190.5] vs 173.4 [95% CI 170.4-176.5], RR 0.93 [95% CI 0.91-0.94]), and intracerebral hemorrhage (28.5 [95% CI 27.3-29.8] vs 22.8 [95% CI 21.7-23.9], RR 0.80 [95% CI 0.76-0.84]). In ischemic stroke the rate of stroke unit care increased significantly (55.7% vs 69.3%; RR 1.14 [95% CI 1.12-1.17]), and acute 1-year recurrences decreased significantly. Discussion: We found a decline of the annual age-adjusted cumulative hospitalization rates in stroke/TIA, a higher age of disease manifestation and less severe strokes, which is probably attributable to improved primary and secondary prevention in Austria. The proportion of patients treated at stroke units increased significantly, however a geographical and age-dependency is still evident. Conclusion: Age-adjusted hospitalization rates of stroke/TIA patients decreased, and stroke unit care is increasing but the goal of the Stroke Action Plan for Europe is yet to be reached.

Reconstruction of pseudonymized patient-trajectories in Austria's stroke cohort using medical record-linkage of in-patient routine documentation to establish a nation-wide acute stroke cohort of 102,107 pseudonymized patients between 2015 and 2019.

Introduction: Administrative health data are increasingly used for disease surveillance, quality assurance and research purposes. In Austria, reporting of a standardized dataset is mandatory for each patient. Patients and methods: Routine documentation includes administrative and medical data, including admission and discharge characteristics, disease-diagnosis using ICD-10, medical procedure codes, and coding of involved hospital departments. Since 2015, a three-step pseudonymization on these data is provided including a pseudonym using secure hash algorithm 256, a non-recalculable record-ID, and age-groups of 5 years, allowing the reconstruction of individual patient-trajectories. We included persons aged ⩾20 years with an in-patient treatment in Austrian hospitals for acute stroke or transient ischemic attack (TIA) between 01.01.2015 and 31.12.2019 using medical record-linkage. Results: This totals 102,107 patients (49.3% women) with 107,055 treatment episodes. An ischemic stroke (IS) occurred in 60.9% (n = 65,133), 27.1% (n = 29,019) had a TIA, 3.3% (n = 3488) a subarachnoid hemorrhage, and 8.8% (n = 9415) an intracerebral hemorrhage (ICH). The study period covers 35.2 million person-years at risk, with a hospitalization rate for acute stroke of 221.8 per 100,000 person-years (95% CI 220.2-223.3), and 185.1 per 100,000 person-years (95% CI 183.7-186.5) for IS. Unscheduled re-admissions within 1 year occurred in 29.2% (95% CI 28.8-29.7) after IS, and 41.7% (95% CI 40.0-43.3) after ICH. Recurrent stroke occurred in 5.3% (95% CI 5.1-5.5) after IS, and 5.6% (95% CI 4.9-6.4) after ICH. Discussion: We present herein the details of a novel methodology to establish a nation-wide unselected Austrian stroke cohort, and to reconstruct pseudonymized individual longitudinal patient-trajectories on a national level. This approach shows potential applications in epidemiological research, quality assessment and outcome measurement. Conclusion: This novel approach opens new research fields, facilitates international comparison, and is needed for national benchmarking to assess the achievement of goals according to the Stroke Action Plan for Europe and augment the quality of Austria's integrated stroke care.

Endometrioid endometrial carcinoma of no-specific-molecular-profile with multiple bone metastases and muscle involvement: Case report and review of the literature.

Bone metastasis and muscular involvement in endometrial carcinoma are rare, and information on molecular profiles of endometrial carcinoma with bone metastasis is scarce. We present a case of an 83-year old woman with a poorly differentiated endometrioid adenocarcinoma of no-specific-molecular-profile with para-aortic lymph node involvement, who underwent surgery, received adjuvant chemotherapy and vaginal brachytherapy but declined external beam radiotherapy. Fifteen months after the initial diagnosis she presented with pain in her right leg. Imaging showed an osteolytic lesion in the right femur with soft-tissue involvement. She underwent an open biopsy and protective osteosynthesis. Histologically, infiltrates of both bone and muscle were consistent with metastasis derived from endometrioid endometrial carcinoma. She received concomitant palliative chemotherapy and external beam radiotherapy to the right femur. Eleven months later, she presented with an acute hemiparesis caused by a right-sided subacute, superior frontal gyrus infarct, which also showed aggressive bone metastasis of the left sphenoid bone. She subsequently died 2 weeks later. This is a rare case of multiple bone metastases and muscle involvement in endometrial carcinoma. To our knowledge, this is the first reported such case in endometrial carcinoma showing no-specific-molecular-profile.

Ulcerative reflux esophagitis associated with Clostridium ventriculi following hiatoplasty - is antibiotic treatment necessary? A case report.

Clostridium (C.) ventriculi (known as Sarcina ventriculi) is a ubiquitous gram-positive, anaerobic, acidophilic coccus found in patients with gastric motility disorders. The microorganisms can be identified histologically by their characteristic presentation in tetrads or packets of 8 in hematoxylin and eosin stains. Severe cases of emphysematous gastritis or gastric perforation have been described. Nevertheless, the significance of C. ventriculi in an upper gastrointestinal tract and its pathogenic character remain unclear. We present a 67-year-old woman who underwent hiatoplasty with gastropexy. After 3 months, she underwent a gastroscopy showing gastroesophageal reflux. Biopsies showed ulcerative reflux esophagitis with presence of C.ventriculi, subsequently confirmed by 16S ribosomal RNA gene amplicon sequencing. The barium swallow study revealed an atonic stomach with delayed gastric emptying. The patient was treated with PPI and domperidone. On follow up, 15 months post-operatively, a control gastroscopy showed a stomach with food residues and reflux-associated small erosions. The Clostridium organisms were detected only in oxyntic mucosa biopsies without erosions or ulcerations. We speculate that the recognition of the organisms in the biopsy material is important and suggests dysmotility disorder. However, in our opinion, the presence of C. ventriculi, even in combination with mucosal damage, does not necessarily prompt antibiotic treatment since no complications occurred and inflammation as well as gastric function improved under PPI and prokinetic therapy in our patient. Larger study groups with long-term follow-up are needed to understand whether these organisms could behave as pathogens or are only bystanders in the setting of delayed gastric emptying.

Prognostic value of cyclin A2 and B1 expression in lung carcinoids.

Carcinoid classification in the lung is still based on morphological criteria. Although there are many studies investigating the role of Ki-67 proliferation index in the classification of lung neuroendocrine tumours, it is still not used in routine diagnostics. Interestingly, cyclins, which have a crucial role in controlling the cell cycle, have not been thoroughly studied in lung neuroendocrine tumours. The aim of our study was to investigate the correlation of cyclin A2 and B1 expression with prognosis, Ki-67 proliferation index, and carcinoid morphology. A cohort of 134 resected typical and atypical carcinoids was stained with antibodies against Ki-67, cyclin A2 and B1. The positive nuclear reaction was assessed in hot spot areas and expressed as the percentage of tumour cells. Univariate analyses found the highest relative hazard between low and high cyclin A2 expression both with respect to overall survival [hazard ratio (HR)=16; 95% confidence interval (CI) 4.8-51; p=0.0000054], and relapse (HR=8; 95% CI 3.1-21; p=0.00002). In multivariate analysis for overall survival cyclin A2 (HR=10; 95% CI 2.5->100; p=0.0082) and B1 (HR=6.5; 95% CI 1.5-35; p=0.02) remained significant when adjusted for other risk factors, whereas Ki-67 was no longer significant (HR=0.64; 95% CI 0.003-5.5; p=0.65). This suggests that Ki-67 is closer to conventional risk factors for survival than cyclin A2 and B1. Furthermore, the analysis revealed 4 mitoses per 2 mm2 as a more powerful prognostic cut-off than currently accepted 2 mitoses. We have clearly demonstrated that application of cyclin A2 and cyclin B1 might bring additional value regarding the overall and progression-free survival of patients with carcinoids of the lung.

Analysis of Social Determinants of Health and Disability Scores in Leprosy-Affected Persons in Salem, Tamil Nadu, India.

A consistent relationship has been found between leprosy and inequities in social determinants of health. It, however, remains unclear which aspect of these social determinants contributes most to the risk of infection, and even less clear are the risk factors for the development of leprosy-related disabilities. The objective of this study was to elicit the differential impact of social determinants of health in leprosy-affected persons, and determine whether structural inequities in accessibility to societal resources and lower socioeconomic parameters correlated with higher severity of disabilities. This analysis was based on a sampled population affected by leprosy in Salem, Tamil Nadu, India. Persons enrolled in the study were covered by a nongovernmental lifelong care program, had completed a multidrug therapy for leprosy and/or were slit-skin-smear negative, and showed Grade 1 or higher disabilities due to leprosy. Multiple stepwise linear regression analysis was performed. The Eyes-Hands-Feet (EHF) score was the outcome variable, and gender, age, time after release from treatment, monthly income, and living space were explanatory variables. There were 123 participants, comprised of 41 (33.33%) women and 82 (66.67%) men. All study participants belonged to India's Backward classes; 81.30% were illiterate and the average monthly income was 1252 Indian rupee (INR) (US$19.08 or €17.16). The average EHF score was 7.016 (95% CI, 6.595 to 7.437). Stepwise multiple linear regression analysis built a significant model, where F(2, 120) = 13.960, p ≤ 0.001, effect size (Cohen's f2) = 0.81, explaining 18.9% of the variance in EHF scores (R² = 0.189). Significant predictors of a higher EHF score in persons affected by leprosy were found to be higher age (beta = 0.340, 95% CI, 0.039 to 0.111, p < 0.001), as well as less living space (beta = -0.276, 95% CI, -0.041 to -0.011, p = 0.001). Our results suggest that inequalities in social determinants of health correspond to higher disability scores, which indicates that poor living standards are a common phenomenon in those living with leprosy-related disabilities. Further research is needed to dissect the exact development of impairments after release from treatment (RFT) in order to take targeted actions against disability deterioration.

Trends and Economic Impact of Hip and Knee Arthroplasty in Central Europe: Findings from the Austrian National Database.

Arthroplasty registers were originally established in Scandinavia to receive clinically relevant information from pooled data, to improve quality and reduce revision surgeries, with socioeconomic benefit. In Austria, where the highest rate of total knee arthroplasties (TKA) per inhabitant of all OECD countries was reached in 2014, arthroplasties are centrally reported since 2009. Study purpose was to perform the first analysis of the Austrian database, aiming to obtain data on trends in arthroplasty in Austria over time in relation to demographic development. Between 2009 and 2015 an almost continuous increase of total hip arthroplasties (THA; 18.052) by 14% and TKA (17.324) by 13% were observed, representing 210 THA and 202 TKA per 100k inhabitants in 2015. A similar increase was found for revision surgeries, with 1.290 re-implanted THA (7.1% of all THA) and 919 re-implanted TKA (5.3% of all TKA) in 2015. Implantation of mega or tumor prosthesis for the knee and hip joint remained constant and was mainly performed in two university hospitals. Patellar resurfacing decreased by 31.6%. Demographic development will further increase the number of primary and revision surgeries. Inclusion of more detailed information on used and revised components was established and will improve efficacy in quality control.