Independent Risk Factors For Recurrence Research Articles

Beyond Sedlis—A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis

PurposeThe Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. MethodsWe performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. ResultsWe identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12–2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67–4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81–10.26; deep 1/3, HR 7.05, CI 2.99–16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25–17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. ConclusionsCurrent treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.

Beach Chair Versus Lateral Decubitus Positioning for Primary Arthroscopic Anterior Shoulder Stabilization: A consecutive series of 641 shoulders

Objectives:There are no studies that directly compare beach chair (BC) versus lateral decubitus (LD) position for anterior instability. In the only systematic review evaluating BC vs LD, bone loss is not accounted for in the recurrence rate. The purpose of this is to identify predictors of shoulder instability recurrence and revision after anterior shoulder stabilization surgery in a young, high demand population and evaluate surgical position and glenoid bone loss as independent predictors of the outcomes of interest, recurrence and revision.Methods:A consecutive series of 641 arthroscopic Bankart stabilizations were performed by sports-medicine certified and fellowship trained orthopaedic surgeons from 2009-2016 in either the BC or LD position. Patients were included if they underwent an isolated primary arthroscopic anterior capsulolabral repair. Patients were excluded if concomitant labral repair and/or Remplissage procedures were performed at the time of surgery. Shoulders were additionally excluded if magnetic resonance imaging (MRI) was not available at the time of preoperative evaluation or the patient was lost to follow-up. All shoulders were evaluated for glenohumeral bone loss using the perfect circle technique on the sagittal en-face MRI as well as for bipolar lesions according to the on/off-track method of Diagacomo et al. Glenoid bone loss was grouped into three categories: <5%, 5-13.5%, and >13.5%. The primary outcomes of interest were recurrent instability and revision stabilization. Recurrent instability was defined as the presence of a recurrent subluxation and or dislocation event and/or the presence of a positive apprehension. Multivariable logistic regression models were used to assess the relationships of outcomes with age, position, glenoid bone loss group, and, track.Results:641 shoulders with a mean age of 22.3 years (SD 4.46) underwent isolated arthroscopic Bankart repair and were followed for a mean 6 years. The overall recurrent instability and revision rates were 15.7% (101/641) and 11.5% (74/641). Recurrent instability was observed in 15.6% (24/154) and 15.9% (77/487) of LD and BC shoulders, respectively. After adjusting for confounders, multivariable logistic regression found no association between surgical position and recurrent instability (p=0.85). Age was an independent predictor for recurrence. The odds of recurrence were 1.58 times higher per 4.5 years (1 standard deviation) decrease in age (P<0.01, 95% CI 1.02 to 1.72). In a separate multivariable logistic regression model of revision surgery as the dependent variable, revision surgery was not associated with age, surgical position, glenoid bone loss group, or recurrence.Conclusions:Among fellowship-trained orthopaedic surgeons the overall failure of primary arthroscopic anterior shoulder stabilization was 15.7% in a high-demand population and equivalent outcomes may be anticipated with arthroscopic Bankart repair performed in the BC or LD position. In multivariable analysis, younger age, but not surgical position, was an independent risk factor for recurrence.

Impact of the prognostic nutritional index on the recurrence of hepatocellular carcinoma patients after curative resection

The purpose of this retrospective study was to determine the association between the prognostic nutritional index (PNI) and recurrence of hepatocellular carcinoma after curative resection. Between 2007 to 2019, 130 patients who underwent curative hepatectomy for hepatocellular carcinoma were enrolled. The PNI was calculated, and the cutoff value was identified through receiver operating characteristic curve analysis. According to the PNI, patients were divided into two groups. Univariate and multivariate analyses were performed to identify independent risk factors for recurrence. The cutoff value of the PNI was 52. In the univariate analysis, alcoholic liver cirrhosis (p = 0.041), protein induced by vitamin K antagonist-II ≥ 200 (p = 0.012), indocyanine green retention test (ICG R15) > 10% (p = 0.001), estimated blood loss ≥ 800 mL (p = 0.037), tumor size (p = 0.001), microvascular invasion (p = 0.023), T-stage (p = 0.001), and PNI < 52 (p = 0.001) affected recurrence. In the multivariate analysis, alcoholic liver cirrhosis (p = 0.046), ICG R15 > 10% (p = 0.025), T-stage (p = 0.003), and PNI < 52 (p = 0.046) were independent prognostic factors for disease-free survival. The PNI, a nutritional and immunologic factor, is an independent prognostic factor that can predict the recurrence of hepatocellular carcinoma in patients undergoing curative resection.

Prognosis and Outcomes in Early Stage Glottic Carcinoma Involving the Anterior Commissure Treated with Laser CO2 Surgery: A Retrospective Observational Analysis.

The anterior commissure (AC) is the area where the vocal cords attach to the thyroid cartilage through Broyles' ligament. Many authors argue that involvement of the anterior commissure in early stage glottic carcinoma (I, II) constitutes a risk factor for local recurrence. The objective of this study is to evaluate whether anterior commissure involvement in early stage glottis cancer is an independent risk factor for recurrence and mortality. The study included all those patients diagnosed with glottis carcinoma in stages I and II of the AJCC treated by transoral laser surgery at the Hospital San Pedro (Logroño, Spain) between 2005 and 2015. Patients were divided into two groups according to the presence (AC1) or absence (AC0) of involvement of the commissure. Of 29 patients treated, 44.8% were AC1. Patients with anterior commissure involvement had more local recurrence (p = 0.2701); higher mortality rate (p = 0.2256); lower disease-free survival (p = 0.0881) and a lower overall survival (p = 0.0331). The 5-year survival rate was 24.5% lower in patients with invasion of the anterior commissure. The involvement of the anterior commissure is an independent risk factor that should be considered in the prognosis of laryngeal cancer.

Association of histological subtype with risk of recurrence in craniopharyngioma patients: a systematic review and meta-analysis.

It is controversial whether there is a different risk of recurrence between two histological subtypes in craniopharyngioma (CP) patients. Some reported that adamantinomatous craniopharyngioma (ACP) had a higher risk of recurrence than papillary craniopharyngioma (PCP), but others reported that there is no significant difference between them. So, we conducted this systematic review and meta-analysis to determine the association between the histological subtype of CP and the rate of recurrence. A comprehensive literature search was undertaken in PubMed, EMBASE, and Web of Science for all English articles published up to November 2020. Recurrence data stratified by ACP and PCP were extracted from studies meeting inclusion criteria. A pooled analysis of the association between the histological subtype of craniopharyngioma and rates of recurrence was performed. Thirteen articles containing 974 patients were included. When stratified by two pathological subtypes, the total recurrence rate of ACP was 26.0% and PCP was 14.1%, which showed ACP associated with a higher risk of tumor recurrence than PCP (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.36, 3.30, P = 0.00). This is the first meta-analysis focusing on histological subtypes of CP. PCP associates with a lower risk of recurrence than ACP, indicating that ACP could act as one of recurrence risk factors for CP patients. Nevertheless, large sample size and well-designed multicenter studies in which the other clinical variables are controlled to determine the histological subtype of CP as an independent recurrence risk factor are needed.

Value of combined detection of ITGA4 and SFRP2 gene methylation in stool DNA in diagnosis and prognostic evaluation of colorectal tumors

To investigate the value of quantitative detection of ITGA4 and SFRP2 gene methylation in stool DNA for the early diagnosis and prognostic evaluation of colorectal tumors. Real-time PCR was used for quantitative assessment of ITGA4 and SFRP2 gene methylation levels in stool samples of 85 patients with colorectal cancer, 65 patients with colorectal adenoma and 40 healthy subjects. The 3 groups were comparable for age and gender composition. Methylated ITGA4 and SFRP2 promoters were detected in 48.2% and 62.4% of patients with colorectal cancer, respectively, with a combined positivity of 81.2%. ITGA4 and SFRP2 promoter methylation was detected in 23.1% and 43.1% of patients with colorectal adenoma, respectively, with a combined positivity of 69.2%. The positivity rates of ITGA4 and SFRP2 methylation were significantly higher in patients with colorectal cancer than in those with colorectal adenoma (P < 0.001; P= 0.001) and healthy subjects (P < 0.001; P < 0.001). In colorectal cancer group, ITGA4 and SFRP2 promoter methylation levels were correlated with postoperative tumor recurrence in colorectal cancer group, and the relapse-free survival rate was significantly lower in positive patients for ITGA4 and SFRP2 promoter methylation than in the negative patients (P=0.0002; P=0.007). Multivariate analysis with the COX proportional hazard regression model showed that methylation of ITGA4 and SFRP2 gene promoters (P=0.01) and the degree of tumor differentiation (P=0.03) were associated with the recurrence of colorectal cancer, and were independent risk factors for the recurrence of colorectal cancer. Combined detection of ITGA4 and SFRP2 gene methylation levels in stool DNA can improve the early diagnosis rate of colorectal tumor. ITGA4 and SFRP2 promoter methylation and the degree of tumor differentiation are independent risk factors for colorectal cancer recurrence.

Preoperative Routine Laboratory Markers for Predicting Postoperative Recurrence and Death in Patients with Breast Cancer.

Simple, convenient, and reliable preoperative prognostic indicators are needed to estimate the future risk of recurrences and guide the treatment decisions associated with breast cancer. We evaluated preoperative hematological markers related to recurrence and mortality and investigated independent risk factors for recurrence and mortality in patients after breast cancer surgery. We reviewed electronic medical records of patients with invasive breast cancer diagnosed at our tertiary institution between November 2005 and December 2010 and followed them until 2015. We compared two groups of patients classified according to recurrence or death and identified risk factors for postoperative outcomes. Data from 1783 patients were analyzed ultimately. Cancer antigen (CA) 15-3 and red cell distribution width (RDW) had the highest area under the curve values among several preoperative hematological markers for disease-free survival and overall survival (0.590 and 0.637, respectively). Patients with both preoperative CA 15-3 levels over 11.4 and RDW over 13.5 had a 1.7-fold higher risk of recurrence (hazard ratio (HR): 1.655; 95% confidence interval (CI): 1.154–2.374; p = 0.007) and mortality (HR: 1.723; 95% CI: 1.098–2.704; p = 0.019). In conclusion, relatively high preoperative RDW (>13.5) and CA 15-3 levels (>11.4) had the highest predictive power for mortality and recurrence, respectively. When RDW and CA 15-3 exceeded the cut-off value, the risk of recurrence and death also increased approximately 1.7 times.

Residual Thyroid Tissue on Postoperative Diagnostic 131 I Radioactive Whole-Body Scan After Surgery in Differentiated Thyroid Cancer: A Tertiary Referral Centre Experience.

Residual thyroid tissue after total thyroidectomy in differentiated thyroid cancers is considered an independent risk factor for recurrence. Guidelines recommend following up patients after surgery with thyroglobulin (Tg), neck ultrasonography, and occasionally whole-body radioactive scan. However, the results of serum thyroglobulin and whole-body radioiodine scan are often discordant. The present study was undertaken to determine the levels of serum-stimulated thyroglobulin to complement the findings of residual thyroid tissue in the radioactive whole-body scan. One hundred twenty-six patients had undergone a radioiodine (131 I) whole-body scan (WBS) during the study duration, and 121 were available for analysis. The thyroglobulin level (measured by the CLIA method) was recorded at the time of these scans. The data was analysed to determine the level of stimulated thyroglobulin correlating with residual thyroid tissue, locoregional, and distant metastasis as assessed by WBS. The presence of residual thyroid tissue was noted in an overwhelmingly high 94% of cases. Twenty-four of the 28 patients with stimulated Tg < 2ng/dl had residual thyroid tissue on a WBS. The discordancy rate (positive moderate - large WBS and negative serum thyroglobulin) of 64.28% was seen. Using ROC the serum thyroglobulin cut-offs levels for the loco-regional disease were found to be 27.705ng/dl and 94.770ng/dl for distant metastasis. The results highlight the fact that serum Tg levels cannot be used as an accurate predictor of the extent of the remnant thyroid tissue. Irrespective of the quality of surgery, which was analysed based on the centre and surgical specialty, over 90% of cases had residual thyroid tissue on WBS. The use of only stimulated Tg levels for follow-up may be inaccurate. Serum Tg is a useful test along with radioactive whole-body scans to distinguish local disease, loco-regional disease, and distant metastasis.

Pilonidal sinus disease recurrence at a tertiary care center in Riyadh.

BACKGROUND: Pilonidal sinus disease (PSD) is a chronic inflammatory disease of the sacrococcygeal area. Pilonidal sinus recurrence is a matter of concern to both patients and healthcare providers.OBJECTIVES: Estimate the rate of PSD recurrence in our center and identify any risk factors contributing to disease recurrence.DESIGN: Retrospective.SETTING: Tertiary care center in Riyadh.PATIENTS AND METHODS: All patients who underwent surgery for primary or recurrent pilonidal sinus between 1 January 2016 to 30 June 2019 were included to allow for at least 1-year of follow-up at the time of data collection.MAIN OUTCOME MEASURE: Recurrence rate of PSD and risk factors for recurrence.SAMPLE SIZE AND CHARACTERISTICS: 369 patients: 329 males (89.2%) and 40 (10.8%) females. Median (interquartile range) age was 21 (18-26) years.RESULTS: Of the 369 included patients, recurrence was identified in 84 (22.8%) cases [95% confidence interval (CI) 18.6-27.4], and the mean timing of recurrence was 1.8 (1.6) years after the primary surgery. In a multivariate logistic regression analysis, increased age and post-operative seroma fluid discharge were independent risk factors for recurrence. In contrast, preoperative antibiotic prophylaxis and postoperative hair removal were effective in reducing recurrence. Type of surgery closure had no effect on recurrence, yet primary closure was associated with early onset of recurrence compared to secondary closure (P=.02).CONCLUSION: Our findings on the factors associated with recurrence of PSD are consistent with many reports in the literature. Reported prevalence estimates vary widely.LIMITATION: Single center, small sample size, retrospective.CONFLICT OF INTEREST: None.

Predictive factors for recurrence of papillary thyroid carcinoma: analysis of 4,085 patients.

SUMMARYObjectiveThe incidence of papillary thyroid carcinoma (PTC) has increased in recent years and its treatment remains controversial. The objective of this study is to identify clinicopathological predictive factors of tumour recurrence.MethodsWe retrospectively analysed 4,085 patients who underwent thyroidectomy for PTC from 1996 to 2015. Patients were stratified according to American Thyroid Association (ATA) risk categories and clinicopathological features were evaluated to identify independent factors for recurrence.ResultsAfter a mean follow-up of 58.7 (range 3-256.5) months, tumour recurrence was diagnosed in 176 (4.3%) patients, mostly in lymph nodes. Distant metastasis occurred in 18 patients (0.4%). There were 3 (0.1%) cancer-related deaths. Multivariate analysis showed that tumour size >10 mm, multifocality, extrathyroidal extension and lymph node metastasis (all, P < 0.001) were independent risk factors for recurrence. Further, recurrence was identified in 1.6% of the ATA low-risk, 7.4% of the intermediate-risk and 22.7% of the high-risk patients (P < 0.001).ConclusionsIn PTC patients, tumour size >10 mm, multifocality, extrathyroidal extension and presence of lymph node metastasis as well as the ATA recurrence staging system effectively predict recurrence.

Recurrence Outcomes Less Favorable in T1 Rectal Cancer than in T1 Colon Cancer.

With the implementation of screening programs worldwide, diagnosis of early-stage colorectal cancer steadily increased, including T1 cancer. Current T1 cancer treatment does not differ according to anatomic location. We therefore compared the disease-free survival of T1 cancer arising from the rectum versus the colon. The hospital-based study included subjects with T1 cancer at National Taiwan University Hospital from 2005 to 2014. Clinical, colonoscopy, and histopathology were reviewed for patients with a mean follow-up time of 7.1 (0.7-12.9) years. We conducted Kaplan-Meier analysis to compare the risk of recurrence by cancer location and Cox regression analysis to identify risk factors for T1 cancer recurrence. The final cohort included a total of 343 subjects with T1 cancer (mean age, 64.9± 11.7 years; 56.1% male), of whom 25 underwent endoscopic resection alone. Of the subjects who underwent surgery, 50 had lymph node metastasis and 268 did not. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer (p=.022). Rectal location and larger neoplasm size were independent risk factors for recurrence, with hazard ratios of 4.84 (95% confidence interval, 1.18-19.92), and 1.32 (95% confidence interval, 1.06-1.65), respectively. The occurrence of advanced histology did not differ between T1 rectal and colon cancers (p=.58). T1 cancers arising from the rectum had less favorable recurrence outcomes than those arising from the colon. Further studies are needed to examine whether adjuvant radiotherapy or chemotherapy can reduce the risk of recurrence in T1 rectal cancer. Current T1 colorectal cancer treatment and surveillance do not differ according to anatomic location. Clinical, colonoscopy, and histopathology were reviewed for 343 patients with T1 cancer with a mean follow-up time of 7.1 years. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer. Moreover, the rectal location was an independent risk factor for recurrence. T1 cancers from the rectum had less favorable recurrence outcomes than those arising from the colon. It is critical to clarify whether adjuvant therapy or more close surveillance can reduce recurrence risk in T1 rectal cancer.

Intraoperative hematoma volume can predict chronic subdural hematoma recurrence.

Background: We routinely measured the exact chronic subdural hematoma (CSDH) volume during single burr hole surgery. To date, several risk factors have been reported for CSDH recurrence, including sex, hematoma volume and degree of midline shift calculated from computed tomography, use of anticoagulants or antiplatelet medications, and alcohol consumption habits. The aim of this study was to clarify whether hematoma volume, in conjunction with other factors, can predict recurrence.Methods: We retrospectively reviewed the clinical data of 194 consecutive patients with CSDH who underwent single burr hole surgery. The risk factors for recurrence were analyzed based on patients’ sex, age, bilaterality, existence of apparent trauma history, exact intraoperative hematoma volume, and various clinical factors, including preoperative anticoagulant/antiplatelet intake.Results: Recurrence occurred in 22 patients (11.3%). Multivariate logistic regression analysis revealed that intraoperative hematoma volume was an independent risk factor for CSDH recurrence (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.01–1.02, P < 0.001), in addition to sex (male) (OR 9.25; 95% CI, 1.00–84.8; P = 0.049) and diabetes mellitus (DM) (OR: 3.97, 95% CI, 1.34–11.7, P = 0.013). Based on receiver operating characteristics analysis, the cutoff value of the hematoma volume predicting CSDH recurrence was 150 ml (sensitivity and specificity of 72.7% and 72.1%, respectively; area under the curve: 0.7664, 95% CI: 0.654–0.879, P < 0.001). Of these, a hematoma volume ≥150 mL was the strongest independent risk factor for recurrence according to multiple regression (OR: 8.98, 95% CI: 2.73–29.6, P < 0.001) and Cox regression analysis (hazard ratio: 3.05, 95% CI: 1.18–7.87, log-rank P = 0.0046, P = 0.021). Follow-up periods after surgery were significantly longer for cases with recurrence than for non-recurrence cases (24.8 ± 11.5 vs. 15.9 ± 9.7 days), and the recurrence prediction cutoff value was 17 days, with a sensitivity and specificity of 83.1% and 68.2%, respectively (AUC: 0.7707, 95% CI: 0.6695–0.8720, P < 0.001).Conclusion: Intraoperative hematoma volume could be a predictive value for CSDH recurrence.

One-Stage Buccal Mucosal Graft Urethroplasty for Lichen Sclerosus-Related Urethral Stricture Disease: A Systematic Review and Pooled Proportional Meta-Analysis.

Performing 1-stage urethroplasty in patients with urethral strictures caused by lichen sclerosus (LS) is hotly debated among reconstructive urologists due to conflicting reports of success. Therefore, the objective of this study was to determine the pooled incidence of stricture recurrence following 1-stage buccal mucosal graft (BMG) urethroplasty in patients with LS, to determine the impact of surgical technique on recurrence and to compare recurrence risk between patients with and without LS after 1-stage repairs. A systematic review was conducted in accordance with PRISMA criteria. The primary outcome was pooled incidence of recurrence, which was calculated using a Der-Simonian-Laird binary random effects model with a Freeman-Tukey arcsine transformation. A total of 21 studies were included, of which 15 provided data for comparative analyses. Pooled data from 625 LS patients revealed a stricture recurrence rate of 10% (95% CI 6-14). Among studies with longer followup (≥24 months), this increased to 18%. Among patients with penile urethral involvement, studies utilizing a penile skin incision had significantly higher pooled recurrence rates than those utilizing penile invagination (p=0.004). Across all studies, there was no evidence to suggest a difference in pooled recurrence rate between patients with and without LS (p=0.36). However, across only long-term studies, recurrence risk was significantly higher for patients with LS (OR 1.83, p=0.05). One-stage BMG urethroplasty is likely a viable surgical option for patients with LS-related strictures; however, high-quality data are limited. Future multi-institutional, long-term prospective studies are needed to assess durability of 1-stage repair.

UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer

UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 in oxaliplatin resistance in colorectal cancer (CRC) remains unknown. In our study, UPF1 is upregulated in CRC in mRNA and protein levels and overexpression of UPF1 predicts a poor overall survival (OS) and recurrence-free survival (RFS) in CRC patients and is an independent risk factor for recurrence. UPF1 promotes chemoresistance to oxaliplatin in vitro and in vivo. UPF1-induced oxaliplatin resistance can be associated with interaction between zinc finger of UPF1 and Toprim of TOP2A and increasing phosphorylated TOP2A in a SMG1-dependent manner. Moreover, UPF1 maintains stemness in a TOP2A-dependent manner in CRC. Taken together, UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced chemoresistance to oxaliplatin in CRC, which may result from regulation of TOP2A activity and maintenance of stemness. Our findings could provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.

The intra-tumor heterogeneity of ER and HER2 expression in patients with ER-positive and HER2-positive breast cancer.

e12550 Background: ER- positive and HER2-positive (double-positive) breast cancers are known to display significant heterogeneity; however, traditional immunohistochemistry (IHC) only reflects inter-tumor heterogeneity. Studies are needed to demonstrate the intra-tumor heterogeneity of ER and HER2 expression and to further explore its impact. Methods: The retrospective study included three double-positive breast cancer cohorts. Data from a total of 141 patients from The Cancer Genome Atlas (TCGA) and 104 patients from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) were used to investigate the molecular characteristics of double-positive breast cancers at the tissue level via somatic mutation and RNA-seq analyses, while 43 patients treated at our hospital were selected to analyze ER and HER2 expression and localization at a single-cell level using multiple IF. The rH/R was proposed to reflect ER and HER2 expression profiles based on multiple IF or RNA-seq results, as follows: rH/E = HER2+ cell percentage / (ER+ cell percentage + 1) or rH/E = ERBB2 expression quantity / (ESR1 expression quantity + 1). Results: In the first two cohorts, we found that the HER2-enriched subtype displayed unique molecular characteristics, including increased TP53, ERBB3, and PI3KCA mutation rates and the abnormal expression of important signaling pathways (e.g., G2/M cell cycle checkpoint and epithelial mesenchymal transition); The rH/E was a significant index for diagnosing HER2-enriched patients (area under the receiver operating characteristic curve [AUC] = 0.92 and 0.75, both P &lt; 0.0001). In the third cohort, we found that 86 % of the patients contained all four tumor cell types (ER+HER2+, ER+HER2-, ER-HER2+, and ER-HER2- cells); The rH/E was an independent risk factor for recurrence (hazard ratio [HR] = 2.63, P = 0.02) and patients with a rH/E ≥ 1.5 had a significantly shorter 5-year disease-free survival (DFS = 67 % vs. 92 %, P = 0.046). Conclusions: The significant intra- and inter-tumor heterogeneity of double-positive breast cancers is closely related to the prognosis of patients, which is of great significance for precision treatment.

Oncological outcomes according to the treatment modality based on the size of rectal neuroendocrine tumors: a single-center retrospective study.

Owing to an increased number of colonoscopy screenings, the incidence of diagnosed rectal neuroendocrine tumors (NETs) has also increased. Tumor size is one of the most frequently regarded factors when selecting treatment; however, it may not be the determinant prognostic variable. We aimed to evaluate oncological outcomes according to the treatment modality based on the size of rectal NETs. A retrospective analysis was performed on patients who were treated for rectal NETs between March 2000 and January 2016 at the Asan Medical Center, Seoul, Korea. Patients who underwent endoscopic removal, local surgical excision, and radical resection were included. The primary outcome was recurrence-free survival (RFS). Data were specified and analyzed following the 2019 World Health Organization classification (WHO). A total of 644 patients were categorized under three groups according to the treatment modality used: endoscopic removal (n = 567), surgical local excision (n = 56), and radical resection (n = 21). Of a total of 35 recurrences, 27 were local, whereas eight were distant. The RFS rate did not differ significantly between the treatment groups in the same tumor-size group ([Formula: see text]1cm group: P = .636, 1-2cm group: P = .160). For T1 tumors, RFS rate was not different between local excision and radical resection ([Formula: see text]1cm group: P = .452, 1-2cm group: P = .700). Depth of invasion, a high Ki-67 index, and margin involvement were confirmed as independent risk factors for recurrence. Among patients treated with endoscopic removal, endoscopic biopsy was a significant factor for worse RFS (P < .001), while tumor size did not affect the RFS. The current guideline recommends treatment options according to tumor size. However, more oncologically important prognostic factors include muscularis propria invasion and a higher Ki-67 index.

Arrhythmia Recurrence After Atrial Fibrillation Ablation: Impact of Warfarin vs. Non-Vitamin K Antagonist Oral Anticoagulants

Both warfarin and non-vitamin K antagonist oral anticoagulants (NOACs) have pleiotropic effects including anti-inflammatory and anti-fibrotic properties. This study aims to explore whether arrhythmia recurrence after AF ablation is influenced by the choice of oral anticoagulant. We retrospectively studied all patients who underwent primary AF ablation between 2011 and 2017 and divided them into two groups according to the anticoagulant used: Warfarin vs. NOACs. The primary endpoint was atrial tachyarrhythmia recurrence after ablation. Of the 1106 patients who underwent AF ablation in the study period (median age 62.5years; 71.5% males, 48.2% persistent AF), 697 (63%) received warfarin and 409 (37%) received NOACs. After a median of 26.4months follow-up, arrhythmia recurrence was noted in 368 patients in warfarin group and 173 patients in NOACs group, with a 1-year recurrence probability of 35% vs. 36% (log rank P = 0.81) and 5-year recurrence probability of 62% vs. 63% (Log rank P = 0.32). However, NOACs use was associated with a higher probability of recurrence (46% for 1year, 68% for 5years) in patients with persistent AF compared with those taking warfarin (34% for 1year, 63% for 5years; log rank P = 0.01 and P = 0.02 respectively). Multivariate analysis indicated that in patients with persistent AF, use of NOACs was an independent risk factor of atrial tachyarrhythmia recurrence after ablation (HR 1.39, 95% CI 1.07-1.81, P = 0.013). In this large contemporary cohort, overall AF recurrence after ablation was similar with NOACs or warfarin use. However, in patients with persistent AF, NOACs use was associated with a higher probability of arrhythmia recurrence and was an independent risk factor of recurrence at long-term follow-up.

Insulin Resistance and Metabolic Syndrome Increase the Risk of Relapse for Fertility Preserving Treatment in Atypical Endometrial Hyperplasia and Early Endometrial Cancer Patients

Objective: Fertility-sparing treatment for young women with atypical endometrial hyperplasia (AEH) and early endometrial cancer (EC) is a difficult challenge. Insulin resistance (IR) and metabolic syndrome (MetS) are two potentially crucial, but currently enigmatic, factors in the recurrence of AEH and early EC patients. In this study we attempt to elucidate these factors. Methods: A retrospective study was conducted from January 2010 to December 2018. Risk factors for recurrence and complete remission time after recurrence (RCR time) were investigated. ROC curves were built to estimate the accuracy of the metabolic characteristics and Kaplan-Meier (K-M) analysis was used to calculate recurrence-free survival (RFS) for patients with various IR or MetS statuses. Results: A total of 111 AEH or early EC patients met the criteria and were enrolled in our study. Univariate analysis found that BMI ≥25kg/m2 (OR=2.7, 95% CI: 1.1-6.4, P=0.03), IR (OR=9.5, 95% CI: 3.3-27.0, P<0.001), MetS (OR=4.9, 95% CI:1.5-15.5, P=0.008), IR+ and MetS+ (OR=21.0, 95% CI: 4.8-92.7, P<0.001), histological type (OR=3.5, 95% CI: 1.5-7.9, P=0.003), and maintenance treatment (OR=0.3, 95% CI: 0.1-0.6, P=0.005) were all significantly associated with recurrence and longer RCR time. Among these factors, IR and MetS were determined to be two independent risk factors for recurrence. Moreover, using IR and MetS as markers significantly improved the diagnostic accuracy of recurrence for fertility-sparing treatment patients (AUC=0.818, P<0.05) and may play synergistic roles in suppressing treatment. K-M analysis indicated both metabolic features played important roles in RFS (P<0.05). Conclusion: Both IR and MetS were significantly associated with recurrence and longer RCR time in AEH and early EC patients receiving fertility-sparing treatment. Funding Information: This study is supported by National Natural Science Foundation of China (Grant No 81874108, 81672571 and 81802607), Beijing Municipal Natural Science Foundation (Grant No. 7202213) and National Key Technology R&D Program of China (Grant No. 2019YFC1005200 and 2019YFC1005201). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committees of Peking University People’s Hospital (No. 2020PHB063-01).

An 8-gene DNA methylation signature predicts the recurrence risk of cervical cancer.

ObjectiveThis study examined the predictive utility of DNA methylation for cervical cancer recurrence.MethodsDNA methylation and RNA expression data for patients with cervical cancer were downloaded from The Cancer Genome Atlas. Differentially methylated genes (DMGs) and differentially expressed genes were screened and extracted via correlation analysis. A support vector machine (SVM)-based recurrence prediction model was established using the selected DMGs. Cox regression analysis and receiver operating characteristic curve analysis were used for self-evaluation. The Gene Expression Omnibus (GEO) database was applied for external validation. Functional enrichment was determined using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.ResultsAn eight-gene DNA methylation signature identified patients with a high risk of recurrence (area under the curve = 0.833). The SVM score was an independent risk factor for recurrence (hazard ratio [HR] = 0.418; 95% confidence interval [CI] = 0.26–0.67). The independent GEO database analysis further supported the result.ConclusionAn eight-gene DNA methylation signature predictive of cervical cancer recurrence was identified in this study, and this signature may help identify patients at high risk of recurrence and improve clinical treatment.

Management strategies for recurrent pediatric craniopharyngioma: new recommendations.

The goal of this study was to identify the independent risk factors for recurrence or progression of pediatric craniopharyngioma and to establish predictors of the appropriate timing of intervention and best management strategy in the setting of recurrence/progression, with the aim of optimizing tumor control. This is a retrospective cohort study of all pediatric patients with craniopharyngioma who were diagnosed and treated at Boston Children's Hospital between 1990 and 2017. This study was approved by the institutional review board at Boston Children's Hospital. All statistical analyses were performed using Stata software. Eighty patients (43 males and 37 females) fulfilled the inclusion criteria. The mean age at the time of diagnosis was 8.6 ± 4.4 years (range 1.2-19.7 years). The mean follow-up was 10.9 ± 6.5 years (range 1.3-24.6 years). Overall, 30/80 (37.5%) patients developed recurrence/progression. The median latency to recurrence/progression was 12.75 months (range 3-108 months). Subtotal resection with no adjuvant radiotherapy (p < 0.001) and fine calcifications (p = 0.008) are independent risk factors for recurrence/progression. An increase (%) in the maximum dimension of the tumor at the time of recurrence/progression was considered a statistically significant predictor of the appropriate timing of intervention. Based on the identified independent risk factors for tumor recurrence/progression and the predictors of appropriate timing of intervention in the setting of recurrence/progression, the authors propose an algorithm for optimal management of recurrent pediatric craniopharyngioma to increase the likelihood of tumor control.