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Endometrial cancer occurs in up to 29% of women before 40 years of age. Seventy percent of these patients are nulliparous at the time. Decision making regarding fertility preservation in early stage endometrial cancer (ES-EC) is, therefore, a big challenge since the decision between the risk of cancer progression and a chance to parenthood needs to be made. Sixty-two percent of women with complete remission of ES-EC after fertility-sparing treatment (FST) report to have a pregnancy wish which, if not for FST, they would not be able to fulfil. The aim of this review was to identify and summarise the currently established biomolecular and genetic prognostic factors that can facilitate decision making for FST in ES-EC. A comprehensive search strategy was carried out across four databases; Cochrane, Embase, MEDLINE, and PubMed; they were searched between March 1946 and 22nd December 2022. Thirty-four studies were included in this study which was conducted in line with the PRISMA criteria checklist. The final 34 articles encompassed 9165 patients. The studies were assessed using the Critical Appraisal Skills Program (CASP). PTEN and POLE alterations we found to be good prognostic factors of ES-EC, favouring FST. MSI, CTNNB1, and K-RAS alterations were found to be fair prognostic factors of ES-EC, favouring FST but carrying a risk of recurrence. PIK3CA, HER2, ARID1A, P53, L1CAM, and FGFR2 were found to be poor prognostic factors of ES-EC and therefore do not favour FST. Clinical trials with bigger cohorts are needed to further validate the fair genetic prognostic factors. Using the aforementioned good and poor genetic prognostic factors, we can make more confident decisions on FST in ES-EC.

Purpose To identify clinicopathologic, technical, and imaging features associated with neoplastic seeding (NS) following image-guided needle breast biopsy. Methods We performed an institutional review board-approved retrospective review of patients presenting with a new diagnosis of breast cancer or suspicious breast findings requiring biopsy with subsequent diagnosis of NS. The time from biopsy to NS diagnosis was calculated. Histology, grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, T category, and N category were recorded. Biopsy guidance method, needle gauge, and number of passes were reviewed in addition to the mammographic and sonographic features of the primary tumors and the NS. Results Eight cases of NS were identified in 4010 patients. The mean time from biopsy to NS diagnosis was 60.8 days. The most frequent histology was invasive ductal carcinoma (7/8). Six cases were grade 3 (75.0%). Five primary breast cancers were ER, PR, and HER2 negative (62.5%). Seven patients underwent biopsy with ultrasound guidance. Multiple-insertion, non-coaxial ultrasound-guided core-needle biopsy was done in 6 cases. Mammographic presentation of NS was focal asymmetry (3/7 cases), mass (1/7), calcifications only (1/7), or occult (2/7). Sonographic presentation of NS was most often a mass (7/8) with irregular shape (5/7) and without circumscribed margins (6/7) and was occult in 1 case (1/8). NS distribution was subdermal and intradermal. Conclusion High-grade, triple-negative breast cancers and multiple-insertion, non-coaxial biopsies may be risk factors for NS. NS should be suspected on the basis of the superficial and linear pattern of disease progression in these patients.

Background:In systemic sclerosis interstitial lung disease (ILD) is the leading cause of mortality [1]. An important unmet clinical need is the to identify patients at risk to develop ILD early, in order to implement personalized monitoring strategies. Although no predictive algorithm is yet available in clinical care, nailfold capillaroscopy is emerging as a promising candidate biomarker to predict the onset of ILD [2].Objectives:The objective of this study was to evaluate the association between transitions in nailfold capillaroscopy patterns and incident ILD.Methods:Patient data from the EUSTAR database were collected of those patients who had least one ILD-free visit with a documented scleroderma pattern at nailfold capillaroscopy, spanning up to 5 years. The baseline for analysis was established as the first recorded ILD-free visit with a documented scleroderma pattern. Only data of patients fulfilling the following key criteria were included in the analysis: age ≥ 18 years, fulfilling ACR-EULAR classification criteria, disease duration from first non-Raynaud phenomenon ≤ 5 years, HRCT confirmed absence of ILD at baseline, at least one follow-up nailfold capillaroscopy, and a minimal follow-up duration of1 year.Mixed logistic regression models were constructed to assess the association between annual risk of ILD and nailfold capillaroscopy pattern. The model was corrected for a priori defined confounders, namely gender, diffuse cutaneous subtype, Caucasian ethnicity, presence of anti-topoisomerase-I antibodies, presence of anti-RNA polymerase III antibodies, higher age, forced vital capacity % predicted, and diffusing capacity of the lungs for carbon monoxide % predicted. In addition, the other covariates were assessed for confounding with a change-in-estimation model.Results:We identified 275 patients meeting the eligibility criteria, from which 90(33%) patients had an early scleroderma pattern, 135(49%) patients had an active scleroderma pattern, and 50(18%) patients had a late scleroderma pattern. Patients with a more severe nailfold capillaroscopic pattern (i.e. active or late) had an unfavourable disease phenotype (Table 1).In our cohort, 66(24%) of the patients developed ILD after a mean(SD) follow-up period of 2.2(1.2) years. The mixed regression model corrected for the a priori defined confounders as well as for modified Rodnan skin score revealed a rise in the annual risk for incident ILD with worsening severity of nailfold capillaroscopic pattern: OR(95%CI); 3.76(1.99-7.11, p<0.01 (Figure 1). Thus, these results indicate an increased risk for incident ILD after? a transition towards a deteriorating nailfold capillaroscopic pattern, along with a reduced risk for incident ILD when transitioning to an improved nailfold capillaroscopic pattern.Conclusion:In conclusion progression towards a more severe nailfold capillaroscopic pattern is associated with a higher risk to develop ILD, necessitating longitudinal nailfold capillaroscopic assessments to identify patients at risk in the early disease stage.REFERENCES:[1] Elhai M et al., Ann Rheum Dis. 2017;76(11):1897-905.[2] Smith V et al., Autoimmun Rev. 2020;19(9):102619.Acknowledgements:NIL.Disclosure of Interests:Arthiha Velauthapillai: None declared, C.H.M. van den Ende: None declared, Madelon Vonk Boehringer Ingelheim, GSK, Janssen, MSD, Novartis, Boehringer Ingelheim, Janssen, Unrestricted research grants from Boehringer Ingelheim, Ferrer and Galapagos.

Background: Alopecia areata (AA) is a tissue-specific autoimmune disease characterized by non-scarring and rapid onset of hair loss. Interleukin (IL)-17A is mainly produced by T helper 17 (Th17) cells and may play a crucial role in the pathogenesis of various autoimmune diseases including AA.Objectives: We conducted this research to measure serum level of IL-17A in patients with AA and investigated its relationship with the clinical manifestations in patients with AA.Methods: We assessed 36 patients with AA and 20 healthy control subjects. Demographic information and clinical characteristics were determined by physical examination and via the review of medical history. Serum IL-17A was measured by using enzyme-linked immunosorbent assay.Results: Serum IL-17A concentration was significantly higher in patients with AA than in the control group (P=0.004). The AA patients with severe presentation, personal atopy, nail abnormalities, or active phase had significantly higher serum IL-17A levels compared to others without these signs.Conclusion: Increased serum IL-17A levels in patients with AA correlate with severity and indicate an active disease state. These findings suggest that IL-17A may play an important role in determining the pathogenesis of AA and may serve as a valuable clinical biomarker of this disease.

Recently, a global phase III study demonstrated that nivolumab markedly improved patient outcomes in recurrent or metastatic head and neck carcinoma (RMHNC). However, the efficacy of nivolumab in patients who are ineligible for clinical trials is unknown. We investigated nivolumab efficacy in real-world patients and prognostic factors associated with the response to nivolumab. This study was conducted at 11 institutes associated with Kyoto University and its Affiliated Hospitals-Head and Neck Oncology Group. In total, 93 patients with RMHNC who received nivolumab between May 2017 and May 2018 were retrospectively reviewed. Objective response rate (ORR), overall survival, and progression-free survival (PFS) were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. The ORRs in patients with squamous cell carcinoma (SCC) and non-SCC were 21.8% and 0%, respectively. In patients with SCC and non-SCC, the 1-year PFS rates were 28.7% and 8.9%, respectively. The hazard ratio (HR) for risk of PFS events (SCC versus non-SCC) was 2.28 (95% confidence interval: 1.21–4.1; log-rank p = 0.007). Univariate and multivariate analyses revealed radiotherapy history, platinum-refractory carcinoma, and treatment-related adverse events (TRAEs) as important prognostic factors associated with PFS in patients with SCC. In a real-world setting, non-SCC and platinum-refractory carcinoma were associated with a poorer prognosis, and a history of radiotherapy to the primary tumor, and the occurrence of TRAEs were associated with a better prognosis. These findings could be useful for clinicians and patients when selecting a treatment strategy.

This study aims to investigate the effect of different local testicular treatments and validate common prognostic factors on primary testicular lymphoma (PTL) patients. We retrospectively reviewed the clinical records of 32 patients from 1993 to 2017 diagnosed with PTL and included 22 patients for analysis. The Kaplan-Meier method, Log-rank test, and multivariate Cox proportional hazard regression analysis were applied to evaluate progression-free survival (PFS), overall survival (OS), and determine prognosis predictors. The median follow-up time was 30 months. Median OS and PFS were 96 months and 49 months, respectively. In univariate analysis, advanced Ann Arbor stage (III/IV) (P < 0.001), B symptoms (P < 0.001), and extranodal involvement other than testis (P = 0.001) were significantly associated with shorter OS and PFS. In multivariate analysis, Ann Arbor stage was significantly associated with OS (OR = 11.58, P = 0.049), whereas B symptom was significantly associated with PFS (OR = 11.79, P= 0.049). In the 10 patients with the systemic usage of rituximab, bilateral intervention could improve median OS from 16 to 96 months (P = 0.032). The study provides preliminary evidence on bilateral intervention in testes in the rituximab era and validates common prognostic factors for Chinese PTL patients.

Background: Skull base chordoma (SBC) is relatively rare and data on its clinical outcome after surgical resection and adjuvant radiotherapy are still limited. Objective: Analyzing the clinical postoperative outcome of SBC patients and defining prognostic factors regarding current treatment modalities. Methods and Material: In this study, 41 SBC patients from 2001 to 2017 were retrospectively analyzed in this single-center study. Results: The most common clinical symptoms were headache (63%) and problems concerning vision (54%) like diplopia. The follow-up controls took place from 1 to 192 months. The mean survival time for the patients was 123.37 months (95% CI 90.89-155.86). The 5- and 10-year survival rates were 73.3 and 49%, respectively. Regarding the Karnofsky-Performance Scale (KPS), Cox regression showed a significant relationship between the survival rates in the overall study population and pre-surgery KPS (P = 0.004). This was further supported with a positive significant correlation between the pre-surgery KPS and the KPS at the last follow-up (P = 0.039). Conclusion: Statistical analysis showed that repeat surgical resection and radiotherapy could be prognostic factors. Furthermore, we were able to show that mortality decreased by 4.5% with each 10 points increase of pre-surgery KPS. This could be a major prognostic factor when deciding treatment modalities. Nevertheless, further standardized clinical studies with a larger patient population should be carried out to extrapolate prognostic factors and improve treatment modalities.

Purpose Frequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown. Methods Patients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models. Results Eighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence. Conclusion The combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.

ABSTRACT Objective: To determine the prognostic significance of bone marrow fibrosis grade in predicting the outcome of myeloproliferative neoplasms. Study Design: Prospective longitudinal study. Duration and Place of Study: Armed Forces Institute of Pathology, Rawalpindi Pakistan, from Jun 2021 to May 2022. Methodology: A total of 114 patients with myeloproliferative neoplasms were included. Under aseptic conditions, a bone marrow aspiration and a Trephine biopsy were obtained. Following processing, the samples underwent staining with Hemotoxylin and Eosin and Reticulin. The WHO bone marrow fibrosis grading system was used to grade the fibrosis. Clinical findings and haematological parameters documented at initial diagnosis were compared with one-year interval follow-up counts. Results: Out of a total 114, 72(63.2%) were male and 42(36.8%) were female. Generalised weakness and pallor were documented in 51(44.7%) and 27(23.7%), respectively. While splenomegaly and/or hepatomegaly were detected in 61(53.5%) and 27(23.7%), respectively, 16(14.9%) transformed into other MPNs and 3(2.6%) into acute leukemia. People who had higher levels of MF-2 and MF-3 reticulin fibrosis had the worst prognosis when it came to peripheral blood cytopenias, disease progression, and transformation. Conclusion: Myeloproliferative neoplasms are very different from one another in terms of how they look and behave. As the grade of fibrosis rises, there is a high chance that the disease will progress to myelofibrosis or change into acute leukaemia, both of which are very bad for overall survival.

The risk of dementia increases in patients with cognitive impairment. However, it is not clear what factors contribute to the onset of dementia in those with cognitive impairment. In this prospective cohort study, we will investigate the every-five-year incidence of cognitive impairment and prognostic factors for cognitive impairment. The Jidong cognitive impairment cohort was established from April 2012 to August 2015, during which we recruited 5854 healthy participants (55.1% male) older than 45 years (mean, 57 years). Participants received a health examination in the Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation. Baseline data and blood samples were collected. Cognitive impairment was evaluated using the Mini-Mental State Examination, and was defined as a Mini-Mental State Examination score of less than 24. Dementia was assessed using the criteria of Diagnostic and Statistical Manual of Mental Disorders (Fourth edition), the International Working Group criteria, and the Mini-Mental State Examination score. The follow-up will continue until December 2024, during which a prognostic model will be constructed. The primary outcome is the presence/absence of dementia and the secondary outcome is quality of life. Baseline screening results showed the following: (1) Cognitive impairment was apparent in 320 participants (5.5%). These participants will be excluded from the Jidong cohort study, and the remaining participants will be followed up. (2) Of the 320 participants with cognitive impairment, there was a significantly higher prevalence of illiteracy than other education levels (35.9%, P < 0.05). Age, arterial hypertension, alcohol consumption, and passive smoking differed significantly between the cognitive impairment and healthy groups (P < 0.05). Multivariate logistic regression models showed that age (odds ratio [OR] = 1.059, 95% confidence interval [CI]: 1.044-1.074) and arterial hypertension (OR = 1.665, 95% CI: 1.143-2.427) were risk factors for mild cognitive impairment. With the increase of educational level (illiteracy, primary school, junior high school, high school, university, and above), cognitive impairment gradually decreased (OR < 1, P < 0.05). (3) This cohort study has initially screened for several risk factors for cognitive impairment at baseline, and subsequent prospective data will further describe, validate, and evaluate the effects of these risk factors on cognitive impairment and dementia. These results can provide clinical evidence for the early prevention of cognitive impairment and dementia. The study was approved by the Ethics Committee of Kailuan General Hospital of Tangshan City and the Medical Ethics Committee, Staff Hospital, Jidong Oilfield Branch, China National Petroleum Corporation on July 12, 2013 (approval No. 2013 YILUNZI 1).