Independent Prognostic Factor For Recurrence Research Articles

Oral tongue leukoplakia: analysis of clinicopathological characteristics, treatment outcomes, and factors related to recurrence and malignant transformation

ObjectivesThe tongue is identified as a high-risk site for oral leukoplakia and malignant transformation. The purpose of this study is to investigate the clinicopathological characteristics and treatment outcomes of tongue leukoplakia and assess the factors related to recurrence and malignant transformation.Materials and methodsOne hundred and forty-four patients who received carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were analyzed statistically.ResultsThe follow-up period was 54.90 ± 54.41 months. Thirty patients showed postoperative recurrence (20.83%), and 12 patients developed malignant transformation (8.33%). The annual transformation rate was 2.28%. Univariate analysis showed that a history of head and neck cancer, size of lesion area, clinical appearance, and pathology were significant factors for both recurrence and malignant transformation. In the multivariate logistic regression, a history of head and neck cancer and size of lesion area were independent prognostic factors for recurrence, and a history of head and neck cancer was the only independent factor for postoperative malignant change.ConclusionsClinicians should adopt more aggressive strategies for tongue leukoplakia patients with a history of head and neck cancer.Clinical relevanceThese results may help clinicians gain a better understanding of oral tongue leukoplakia.

RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival.

Angiogenesis and immunosuppression have been described as closely related processes that can occur in parallel. As an inhibitor of matrix metalloproteinase, whether the level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in hepatocellular carcinoma (HCC) reflects a link between angiogenesis and immunosuppression is still unknown. We analyzed RNA expression, immune infiltration and survival of HCC from The Cancer Genome Atlas databases. Immune scores and stromal scores were calculated based on the ESTIMATE algorithm to quantify the immune and stromal components in HCC. The association between RECK and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high RECK expression was significantly better than that of patients with low RECK expression. High RECK expression was associated with high ESTIMATE Score, recruitment of more tumor-infiltrating lymphocytes, low tumor purity, and high PD-L1 expression. In addition, positive RECK expression was associated with a lower incidence of vascular invasion and recurrence, a lower level of alpha fetoprotein (AFP) and microvessel density and a better tumor differentiation. Multivariate analyses revealed that reduced RECK expression was an independent prognostic factor for recurrence and poor prognosis. In conclusion, high RECK expression reflects an immunogenic and hypovascularity status in HCC. RECK is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive anti-angiogenic therapy or immunotherapy.

Obesity and high neutrophil-to-lymphocyte ratio are prognostic factors in non-metastatic breast cancer patients.

Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with systemic inflammation have been receiving attention as potential prognostic indicators in cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and invasive breast cancer and the association of NLR, PLR, and BMI with breast cancer outcomes. We undertook a retrospective study to evaluate patients treated for breast cancer over 14 years. Clinicopathological data was obtained before receiving any treatment. Of the 1664 patients included with stage I-III, 567 (34%) were obese (BMI≥30 kg/m2). Obese patients had larger tumors compared to non-obese patients. Higher BMI was associated with recurrence and worse survival only in patients with stage I disease. NLR and PLR were classified into high and low level groups. The NLRhigh (NLR>4) was found to be an independent prognostic factor for recurrence and mortality, while the PLRhigh (PLR>150) group had no impact on survival. A subgroup of patients with NLRhigh and BMIhigh had the worst disease-free survival (P=0.046), breast cancer-specific survival (P<0.001), and overall survival (P=0.006), compared to the other groups. Patients with early-stage breast cancer bearing NLRhigh and BMIhigh had worse outcomes, and this might be explained by the dysfunctional milieu of obesity in adipose tissue and its effects on the immune system. This study highlights the importance of lifestyle measures and the immune system interference with clinical outcomes in the early breast cancer setting.

Role of doublecortin-like kinase 1 and leucine-rich repeat-containing G-protein-coupled receptor 5 in patients with stage II/III colorectal cancer: Cancer progression and prognosis.

BACKGROUNDCancer stem cells (CSCs) are a subpopulation of cancer cells with the potential of self-renewal and differentiation. CSCs play critical roles in tumorigenesis, recurrence, metastasis, radiation tolerance and chemoresistance.AIMTo assess the expression patterns and clinical potential of doublecortin-like kinase 1 (DCLK1) and leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), as prognostic CSC markers of colorectal cancer (CRC). METHODSThe expression of DCLK1 and Lgr5 in CRC tissue sections from 92 patients was determined by immunohistochemistry. Each case was evaluated using a combined scoring method based on signal intensity staining (scored 0-3) and the proportion of positively stained cancer cells (scored 0-3). The final staining score was calculated as the intensity score multiplied by the proportion score. Low expression of DCLK1 and Lgr5 was defined as a score of 0-3; high expression of DCLK1 and Lgr5 was defined as a score of ≥ 4. Specimens were categorized as either high or low expression, and the correlation between the expression of DCLK1 or Lgr5 and clinicopathological factors was investigated.RESULTSDCLK1 and Lgr5 expression levels were significantly positively correlated. CRC patients with high DCLK1, Lgr5 and DCLK1/Lgr5 expressions had poorer progression-free survival and overall survival. Moreover, high expression of DCLK1 was an independent prognostic factor for recurrence and overall survival in patients with CRC by multivariate analysis (P = 0.026 and P = 0.049, respectively).CONCLUSIONDCLK1 may be a potential CSC marker for the recurrence and survival of CRC patients.

Predictive Value of Molecular Subtypes in Premenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the ABCSG Trial 5.

To assess the predictive value of molecular breast cancer subtypes in premenopausal patients with hormone receptor-positive early breast cancer who received adjuvant endocrine treatment or chemotherapy. Molecular breast cancer subtypes were centrally assessed on whole tumor sections by IHC in patients of the Austrian Breast and Colorectal Cancer Study Group Trial 5 who had received either 5 years of tamoxifen/3 years of goserelin or six cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF). Luminal A disease was defined as Ki67 <20% and luminal B as Ki67 ≥20%. The luminal B/HER2-positive subtype displayed 3+ HER2-IHC or amplification by ISH. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Cox models adjusted for clinical and pathologic factors. 185 (38%), 244 (50%), and 59 (12%) of 488 tumors were classified as luminal A, luminal B/HER2-negative and luminal B/HER2-positive, respectively. Luminal B subtypes were associated with poor outcome. Patients with luminal B tumors had a significantly shorter RFS [adjusted HR for recurrence: 2.22; 95% confidence interval (CI), 1.41-3.49; P = 0.001] and OS (adjusted HR for death: 3.51; 95% CI, 1.80-6.87; P < 0.001). No interaction between molecular subtypes and treatment was observed (test for interaction: P = 0.84 for RFS; P = 0.69 for OS). Determination of molecular subtypes by IHC is an independent prognostic factor for recurrence and death in premenopausal women with early-stage, hormone receptor-positive breast cancer but is not predictive for outcome of adjuvant treatment with tamoxifen/goserelin or CMF.See related commentary by Hunter et al., p. 5543.

Quantification of Recurrence Risk Based on Number of Adverse Prognostic Factors in Women with Early Stage Uterine Endometrioid Carcinoma

We sought to quantify the risk of recurrence in women with International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial carcinoma, solely of endometrioid based on the number of adverse prognostic factors We identified 1133 women at our institution who underwent a hysterectomy and did not receive any adjuvant therapy between 1/1990 and 12/2019. Cox proportional hazards model was used to identify independent predictors of recurrence. Prognostic groups were created based on the number of independent predictors of recurrence (0, 1 or 2 or 3 risk factors). Median follow-up was 84 months. Independent prognostic factors of recurrence included age ≥ 60, grade 2/3 and the presence of lymphovascular space invasion (LVSI). Due to small number in groups with 2 or 3 risk factors, these were combined into one group (group 2). Isolated vaginal cuff recurrence was the most common site of recurrence in the study groups (81%, 58% and 70% for groups 0, 1 and 2, respectively). Five-year recurrence rates were 4%, 15%, and 43% for groups 0, 1, and 2 (p<0.001), respectively. Five-year disease-specific survival were 99%, 96% and 85% and 5-year overall survival were 94%, 85% and 63% (p<0.001), respectively. On the basis of 3 well-known prognostic factors, individualized recurrence rate can be predicted in women with stage I endometrial carcinoma. This simplified predictive tool may be helpful in estimating individualized risk of recurrence and guide counseling with regard to adjuvant treatment.

Prognostic Impact of Intra-Ampullary Papillary-Tubular Neoplasm versus Flat Dysplasia as Precursor Lesions of Ampullary Adenocarcinoma

Background: The aim of this study is to compare the prognostic impact of 2 precursor lesions of ampullary adenocarcinoma, intra-ampullary papillary-tubular neoplasm (IAPN) and flat dysplasia (FD). Methods: From December 1994 to December 2012, a total of 359 patients underwent curative surgery for ampullary adenocarcinoma. Results: The precursor lesions were IAPNs in 134 (37.3%) patients and FD in the other 225 (62.7%) patients. The FD group had more aggressive tumor biology with advanced T stage (p = 0.002), nodal involvement (p < 0.001), poor differentiation (p < 0.001), perineural and lymphovascular invasion (p < 0.001), and pancreatobiliary or mixed subtype (p < 0.001). Five-year overall survival rates were 71.1% in the IAPN group and 51.4% in the FD group (p = 0.002), respectively. Five-year disease-free survival rates were 69.7% in the IAPN group and 49.6% in the FD group (p < 0.001), respectively. The recurrence rate was also higher in the FD group (49.8 vs. 30.6%; p < 0.001). On multivariate analysis, higher levels of tumor markers including CEA and CA19-9, lymph node metastasis, poorly differentiated histology, and perineural invasion were negative predictive factors for survival. Higher levels of CEA and CA19-9, lymphovascular invasion, and FD were independent prognostic factors for recurrence. Conclusion: FD was significantly associated with worse prognosis and a greater tendency toward advanced disease. Further studies are needed to clarify the impacts of these precursor lesions.

Predictive Role of Biopsy Based Biomarkers for Radiotherapy Treatment in Rectal Cancer.

Background and Purpose: Radiation therapy has long been contemplated as an important mode in the treatment of rectal cancer. However, there are few ideal tools available for clinicians to make a radiotherapy decision at the time of diagnosis for rectal cancer. The purpose of this study was to assess whether biomarkers expressed in the biopsy could help to choose the suitable therapy and provide predictive and/or prognostic information. Experimental Design: In total, 30 biomarkers were analyzed in 219 biopsy samples before treatment to discover the possibility of using them as an indicator for radiotherapy selection, diagnosis, survival and recurrence. Results: Twenty-two biomarkers (COX2-RT, COX2-NonRT, etc.; 36.67%) had diagnostic value. For survival, four biomarkers (NFKBP65, p130, PINCH and PPAR) were significant in regulating gene promoter activity and overall survival, while four had a trend (AEG1, LOX, SATB1 and SIRT6). Three biomarkers (COX2, PINCH and WRAP53) correlated with disease-free survival, while eight had a trend (AEG1, COX2, Ki67, LOX, NFKBP65, PPAR and SATB1). Four biomarkers (COX2-RT, NFKBP65cyto-RT, P130cyto-NonRT and PPARcyto-RT) were independent prognostic factors for recurrence. NFKBP65 and SIRT6 were significantly correlated with lymph node metastasis regardless of radiation. Patients with high AEG1, LOX, NFKBP65, PPAR and SATB1 had or showed a positive trend for better survival after radiotherapy, while those with positive PINCH and WRAP53 expression would not benefit from radiotherapy. Conclusions: AEG1, LOX, NFKBP65cyto, PPAR and SATB1 could be used as indicators for choosing radiotherapy. COX2-RT, COX2-NonRT and some other biomarkers may provide additional help for diagnosis.

Tumor total lesion glycolysis and number of positive pelvic lymph nodes on pretreatment positron emission tomography/computed tomography (PET/CT) predict survival in patients with locally advanced cervical cancer

ObjectiveThe aim of this study was to investigate the prognostic value of metabolic parameters obtained at pretreatment [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) in patients with locally advanced cervical...

Relationship between post-void residual urine volume, preoperative pyuria and intravesical recurrence after transurethral resection of bladder carcinoma.

To evaluate the relationship between residual urine volume, pyuria and bladder carcinoma recurrence. The clinical data of 305 patients who had post-void residual urine volume measured and preoperative pyuria were retrospectively collected. The patients were classified into three risk groups based on the presence of residual urine and pyuria: good (negative residual urine and pyuria), intermediate (positive residual urine or pyuria) and poor (positive residual urine and pyuria). Predictive factors for intravesical recurrence-free survival were statistically analyzed using Cox proportional hazard models and Kaplan-Meier methods. The propensity score matching method was used to adjust the patients' backgrounds. The median follow-up period for all patients was 44months. The presence of residual urine (P=0.0164) and pyuria (P=0.0233) were two independent prognostic factors for recurrence. After patients were classified into risk groups, the poor-risk group showed significantly shorter recurrence-free survival compared with that of the good- (P=0.0002) and intermediate-risk groups (P=0.0090). Even after matching, the presence of residual urine was related to short recurrence-free survival in male patients (P=0.0012). When stratified by European Organization for Research and Treatment of Cancer risk groups, the presence of pyuria was related to short recurrence-free survival, especially for intermediate-risk patients without bacillus Calmette-Guérin treatment. Post-void residual urine and preoperative pyuria are two risks for recurrence-free survival in non-muscle-invasive bladder cancer.

Evaluation of treatment patterns and prognosis in correlation with age in patients with vulvar cancer: A subset analysis of the AGO-CaRE-1 study.

6090 Background: Despite an increasing incidence with simultaneous decreasing age of onset, the impact of age on prognosis and treatment patterns in primary squamous cell vulvar cancer (VSCC) has not extensively been studied yet. Methods: This is a subgroup analysis of the AGO-CaRE-1 study. Patients (pts) with VSCC (FIGO stage ≥1B), treated at 29 cancer centers in Germany from 1998-2008, were included in a centralized database (n = 1618). In this subgroup analysis pts were analyzed according to age ( &lt; 50yrs (n = 220), 50–69yrs (n = 506), ≥70yrs (n = 521)) with regard to treatment patterns and prognosis. Only pts with documented age, surgical groin staging and known nodal status were included (n = 1247). Median follow-up was 27.5 months. Results: At first diagnosis, women ≥70yrs presented with more advanced tumor stages ( &lt; 0.001), larger tumor diameter ( &lt; 0.001), poorer ECOG status ( &lt; 0.001), higher tumor grading (0.048), as well as a higher rate of nodal involvement ( &lt; 0.001). Older women ≥70yrs showed more commonly HPV negative tumors compared to the other age groups (54% vs. 36.5% in &lt; 50yrs vs. 47.9% in 50-69yrs, p = 0.03). Disease recurrence occurred significantly more often in elderly women (48% vs. 21% in &lt; 50yrs vs. 37.4% in 50-69yrs, p = 0.001). Particularly isolated vulvar recurrence was more frequent in the elderly in comparison to the younger groups (18.2% vs. 15.2% in 50-69yrs vs. 12.7% in &lt; 50yrs, p = 0.001). Age was an independent prognostic factor for disease-free survival (DFS) (HR: 1.7, 95%CI: 1.24-2.46, p = 0.001) with 2-year DFS being 81.1% (&lt; 50yrs), 65.8% (50–69yrs), and 59.3% (≥70yrs), respectively. Elderly women (age group ≥70) had a 221% higher risk for death or recurrence, compared to the youngest group (HR: 3.21, p &lt; 0.001). In a multivariate analysis ECOG, tumor stage, grading, and receipt of (chemo)radiation were further independent prognostic factors for recurrence. Conclusions: Older women with VSCC present with advanced tumor stages at first diagnosis and have an increased risk of recurrence as well as a decreased 2-year PFS in comparison to younger pts groups. Potential reasons for delayed time of diagnosis could be self-awareness and/or more aggressive tumor biology due to HPV negative disease.

Intraparotid node metastases in adults with parotid mucoepidermoid cancer: an indicator of prognosis?

We have retrospectively analysed the predictive value of intraparotid nodal metastases in patients having neck dissection for parotid mucoepidermoid cancer. The main outcomes were intraparotid nodal metastases, a new system for staging metastatic parotid nodes, and recurrence-free survival. The overall rate of intraparotid metastasis was 30/122 (25%), and seven patients had deep parotid nodal metastases. This metastasis was significantly related to tumour stage, neck disease, perineural invasion, lymphovascular invasion, and pathological tumour grade. The sensitivity of intraparotid nodal metastases in predicting neck disease was 50%, and the specificity of them predicting neck disease was 89%. The stages of the intraparotid nodes were as follows: P0 (n=92 patients), P1 (n=10), P2 (n=16), and P3 (n=4). A Cox's model analysis confirmed that the stage of the intraparotid nodes was an independent prognostic factor for recurrence, so the presence of intraparotid nodal metastases is associated with a higher risk for recurrence of disease.

CD47 Expression Is an Independent Prognostic Factor for Recurrence in Resected Non-Small Cell Lung Cancer

Background: Immunotherapy is among the most promising advances in oncology. Limited information exists regarding the interrelationship between CD47 expression and the tumour-associated macrophage-related immune microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy. Methods: CD47 and PD-L1 expression was retrospectively studied in 191 resected NSCLC specimens using immunohistochemistry. Additionally, 46 cases with pulmonary infectious diseases were enrolled as a control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated using dual-immunofluorescence staining. Targeted DNA sequencing was performed on all 191 specimens. Finally, the pattern of immune infiltrates was determined and their prognostic role was assessed. Findings: The prevalence of positive CD47 (CD47pos) expression in NSCLC was 33.0% (63/191), significantly higher than that in pulmonary infectious diseases. CD47pos expression was significantly higher in female, non-smoking, and adenocarcinoma patients (p=0·020, p<0·001, and p<0·001, respectively). Furthermore, CD47pos expression significantly correlated with EGFR mutation (p<0·001). The expression of CD47 (H-score) in NSCLC negatively correlated with tumour PD-L1 expression (p=0·0334) and tumour mutation burden (p=0·0107). CD47pos expression independently correlated with poor disease-free survival (DFS) for patients with NSCLC in multivariate Cox regression analysis (p=0·035). When CD47 and M2 were combined as combinatorial biomarkers, four patient groups were significantly separated (p<0·001), with negative CD47 expression/absence of M2 in the tumour area showing longer DFS and CD47pos expression/M2 therein exhibiting poor DFS. Interpretation: Our study investigated the demographic, molecular, and immuno-microenvironment characteristics of CD47 expression in NSCLC. We further identified tumour CD47pos expression as an independent prognostic factor for recurrence in NSCLC. Our study illustrates the potential value of anti-CD47 treatment in NSCLC. Funding Statement: This study was supported by the ‘13th Five-Year’ National Science and Technology Major Project for New Drugs (No: 2019ZX09734001-002) by the National Natural Science Foundation of Beijing (to YX) (no. 7194311) and the Fundamental Research Funds for the Central Universities (to YX) (no. 3332018030). This study was funded in part by Innovent Biologics (Suzhou) Co., Ltd. Declaration of Interests: MW received partial research funding from Innovent Biologics (Suzhou) Co., Ltd. and Dizal Pharmaceutical Co., Ltd. The other authors declare no conflicts of interest. Ethics Approval Statement: The study protocol adhered to the World Medical Association Declaration of Helsinki recommendations and was approved by the Ethical Committee of PUMCH (S-K146).

Positive tumour CD47 expression is an independent prognostic factor for recurrence in resected non-small cell lung cancer

BackgroundImmunotherapy is a promising advance in oncology. Limited information exists regarding the interrelationship between CD47 expression and tumour-associated macrophage-related immuno-microenvironment in patients with non-small cell lung cancer (NSCLC). These factors may predict novel immunotherapy efficacy.Patients and methodsCD47 and PD-L1 expression was retrospectively assessed in 191 resected NSCLC specimens via immunohistochemistry. Forty-six patients with pulmonary infectious diseases were enrolled as the control group. The infiltration of macrophages (M2 and M1) and CD8+ T-lymphocytes was evaluated via dual-immunofluorescence staining. Targeted DNA sequencing was performed on NSCLC specimens. Survival analysis was performed using the Cox model.ResultsUsing 2+/3+ as a CD47 positive (CD47pos) expression cut-off, the prevalence of CD47pos expression in NSCLC was 33.0% (63/191), significantly higher than in pulmonary infectious diseases. CD47pos expression was significantly higher in female, non-smoking and adenocarcinoma patients (p=0.020, p<0.001 and p<0.001, respectively). Furthermore, CD47pos expression was significantly correlated with epidermal growth factor receptor mutation (p<0.001). The expression of CD47 (H-score) in NSCLC was negatively correlated with tumour PD-L1 expression (p=0.0346) and tumour mutation burden (p=0.0107). CD47pos expression was independently correlated with poor disease-free survival in patients with resected NSCLC in multivariate Cox regression analysis (p=0.035).ConclusionThis study revealed the demographic, molecular and immuno-microenvironment characteristics of CD47 expression in NSCLC. We identified tumour CD47pos expression as an independent prognostic factor for recurrence in resected NSCLC. Our findings illustrate the potential of anti-CD47 treatment in NSCLC.

Significance of nucleoli in invasive carcinoma breast–A novel parameter under study

Background: Breast cancer is the most common female cancer. There are various histomorphological findings which will define the prognosis of tumor like pleomorphism, mitosis, architecture etc. But the role of nucleoli in assessing the prognosis of tumor is rarely studied. Hence in the present study, the significance of nucleoli is studied and its correlation with the size of tumor. Objectives: To find out the significance of nucleoli in assessing the prognosis of the carcinoma breast Material and Methods: The present study is a retrospective study. The total number of cases is 30. Review of all slides has been done mainly aiming to find out the presence or absence of nucleoli and comparison with tumor size. The statistical significance is calculated. Results: It is evident that nucleoli is seen in 33% in tumor stage 1, 77% of cases in tumor stage 2 disease and 77% of cases in tumor stage 3. So as the stage advances (worsens), chances of getting nucleoli are more. The data is not statistically significant due to less number of cases. Discussion: Tumor size is an independent prognostic factor of recurrence of tumor. In the present study it is observed that as the tumor stage increases, there are more chances of appearance of nucleoli. Conclusion: The presence of nucleoli may be considered as one of the poor prognostic factor for invasive breast carcinoma.

Reconsideration of indications for choledochoscopic gallbladder-preserving surgery and preventive measures for postoperative recurrence of gallstones.

IntroductionThe recurrence of cholecystolithiasis after choledochoscopic gallbladder-preserving surgery is a major problem. It is unclear whether the recurrence of cholecystolithiasis is due to the limitations of the operation itself or to the selection of inappropriate candidates.AimTo analyze the recurrence of cholecystolithiasis after choledochoscopic gallbladder-preserving surgery and to provide guidance for the treatment of cholecystolithiasis by choledochoscopic gallbladder-preserving surgery.Material and methodsA total of 145 patients who had undergone choledochoscopic gallbladder-preserving surgery were studied from January 2012 to January 2018. The recurrence rate, recurrence time, and risk factors were evaluated.ResultsOf these 145 patients, 14 (9.66%) experienced recurrence with a mean follow-up time of 39.72 ±24.44 months. The mean time to recurrence was 30.07 ±21.21 months. Univariate analysis showed that pregnancy history (p = 0.008), the uniformity of gallstones (p = 0.002), preoperative inflammation (p = 0.022), postoperative oral drugs (p = 0.022) and the regularity of diet (p = 0.001) were significantly related to recurrence. The uniformity of gallstones (odds ratio (OR) = 0.079; 95% confidence interval (CI): 0.010–0.590; p = 0.013) and the regularity of diet (OR = 0.074; 95% CI: 0.010–0.528; p = 0.009) were independent prognostic factors for recurrence according to multivariate analysis.ConclusionsNonuniform gallstones combined with an irregular diet are significant risk factors that predict cholecystolithiasis recurrence.

Prediction of recurrence and remission using superb microvascular imaging in rheumatoid arthritis.

Ultrasound is commonly used to assess the degree of synovitis in patients with rheumatoid arthritis (RA); however, it is unclear which joints are optimal for evaluating and predicting recurrence and remission. In 293 RA patients enrolled in the KURAMA cohort, 28 joints were assessed by ultrasound. Results from patients in remission in both 2015 and 2017 (Group 1, n = 152) were compared with those from patients in remission in 2015 and non-remission in 2017 (Group 2, n = 60). The SMI scores for total (3.1 vs. 6.3, P = 0.004), MCP2-5 (1.1 vs. 2.4, P = 0.03), wrist (0.9 vs. 2.1, P = 0.0003), MTP2-5 (0.4 vs. 1.0, P = 0.03), and Lisfranc joints (0.07 vs. 0.25, P = 0.04) were significantly higher for Group 2. When those in non-remission in 2015 and remission in 2017 (Group 3, n = 27) were compared with those in remission in 2015 and non-remission in both 2015 and 2017 (Group 4, n = 54), the GS-SMI combined score (3.0 vs. 5.0, P = 0.04) and SMI score (1.5 vs. 2.9, P = 0.04) for MCP2-5 joints were significantly higher for Group 4. Multivariate logistic regression analysis identified "wrist SMI score ≧ 1" as an independent prognostic factor for recurrence (odds ratio 3.08, P = 0.001) and "MCP2-5 GS-SMI combined score ≦ 4" as an independent prognostic factor for remission (odds ratio 3.25, P = 0.048). We identified the optimal joint cut-off scores for predicting recurrence and remission in RA patients. Risk-stratification therapy based on the ultrasound scores may improve outcome and quality of life for patients with RA.

Value of Molecular Classification for Prognostic Assessment of Adrenocortical Carcinoma

The risk stratification of adrenocortical carcinoma (ACC) based on tumor proliferation index and stage is limited. Adjuvant therapy after surgery is recommended for most patients. Pan-genomic studies have identified distinct molecular groups closely associated with outcome. To compare the molecular classification for prognostic assessment of ACC with other known prognostic factors. In this retrospective biomarker analysis, ACC tumor samples from 368 patients who had undergone surgical tumor removal were collected from March 1, 2005, to September 30, 2015 (144 in the training cohort and 224 in the validation cohort) at 21 referral centers with a median follow-up of 35 months (interquartile range, 18-74 months). Data were analyzed from March 2016 to March 2018. Meta-analysis of pan-genomic studies (transcriptome, methylome, chromosome alteration, and mutational profiles) was performed on the training cohort. Targeted biomarker analysis, including targeted gene expression (BUB1B and PINK1), targeted methylation (PAX5, GSTP1, PYCARD, and PAX6), and targeted next-generation sequencing, was performed on the training and validation cohorts. Disease-free survival. Cox proportional hazards regression and C indexes were used to assess the prognostic value of each model. Of the 368 patients (mean [SD] age, 49 [16] years), 144 were in the training cohort (100 [69.4%] female) and 224 were in the validation cohort (142 [63.4%] female). In the training cohort, pan-genomic measures classified ACC into 3 molecular groups (A1, A2, and A3-B), with 5-year survival of 9% for group A1, 45% for group A2, and 82% for group A3-B (log-rank P < .001). Molecular class was an independent prognostic factor of recurrence in stage I to III ACC after complete surgery (hazard ratio, 55.91; 95% CI, 8.55-365.40; P < .001). The combination of European Network for the Study of Adrenal Tumors (ENSAT) stage, tumor proliferation index, and molecular class provided the most discriminant prognostic model (C index, 0.88). In the validation cohort, the molecular classification, determined by targeted biomarker measures, was confirmed as an independent prognostic factor of recurrence (hazard ratio, 5.96 [95% CI, 1.81-19.58], P = .003 for the targeted classifier combining expression, methylation, and chromosome alterations; and 2.61 [95% CI, 1.31-5.19], P = .006 for the targeted classifier combining methylation, chromosome alterations, and mutational profile). The prognostic value of the molecular markers was limited for patients with stage IV ACC. The findings suggest that in localized ACC, targeted classifiers may be used as independent markers of recurrence. The determination of molecular class may improve individual prognostic assessment and thus may spare unnecessary adjuvant treatment.

Effect of Adjuvant Therapy on Oncologic Outcomes of Surgically Confirmed Stage I Uterine Carcinosarcoma: a Turkish Gynecologic Oncology Study

Background:Uterine carcinosarcoma is rare neoplasm that mostly presents as metastatic disease. Stage is one of the most important prognostic factor, however, the management of the early stage uterine carcinosarcoma is still controversial.Aims:To evaluate prognostic factors, treatment options, and survival outcomes in patients with surgically approved stage I uterine carcinosarcoma.Study Design:Cross-sectional study.Methods:Data of 278 patients with uterine carcinosarcoma obtained from four gynecologic oncology centers were reviewed, and 70 patients with approved stage I uterine carcinosarcoma after comprehensive staging surgery were studied.Results:The median age of the entire cohort was 65 years (range; 39-82). All patients underwent both pelvic and paraaortic lymphadenectomy. Forty-one patients received adjuvant therapy. The median follow-up time was 24 months (range; 1-129). Nineteen (27.1%) patients had disease failure. The 3-year disease-free survival and cancer-specific survival of the entire cohort was 67% and 86%, respectively. In the univariate analysis, only age was significantly associated with disease-free survival (p=0.022). There was no statistical significance for disease-free survival between observation and receiving any type of adjuvant therapy following staging surgery. Advanced age (<75 vs ≥75 years) was the only independent prognostic factor for recurrence (hazard ratio: 3.8, 95% CI=1.10-13.14, p=0.035) in multivariate analysis. None of the factors were significantly associated with cancer-specific survival.Conclusion:Advanced age was the only independent factor for disease-free survival in stage I uterine carcinosarcoma. Performing any adjuvant therapy following comprehensive lymphadenectomy was not related to the improved survival of the stage I disease.

Efficacy of Immediate Postoperative Instillation of Chemotherapy for Primary Non-Muscle-Invasive Bladder Cancer in Real-World Clinical Practice.

Non-muscle-invasive bladder cancer (NMIBC) can be treated using transurethral resection (TUR), but high incidence of intravesical recurrence remains a clinical challenge. Single immediate postoperative instillation of chemotherapy (IPIOC) is controversial for NMIBC patients with intermediate recurrence risk. The aim of the present study was to report the efficacy and toxicity of IPIOC, particularly in intermediate-risk NMIBC patients, in the real-world setting. We retrospectively analyzed 363 consecutive patients with primary NMIBC who underwent radical TUR at Kyoto University Hospital between 2007 and2016. In low-risk patients, recurrence-free survival (RFS) was significantly better for IPIOC than non-IPIOC (2-year RFS: 89.3% vs. 59.4%; P= .001). In intermediate-risk patients, IPIOC was associated with significantly longer RFS compared with non-IPIOC (2-year RFS: 85.5% vs. 58.2%; P= .011). IPIOC and bacillus Calmette-Guérin (BCG) were independent predictors for post-TUR recurrence (non-IPIOC vs. IPIOC: hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.14-4.88; P= .02; non-BCG vs. BCG: HR, 2.22; P= .045, 95% CI, 1.02-5.30). In the high-risk group, only BCG was an independent prognostic factor of recurrence in a multivariate Cox proportional hazards model (HR, 2.55; P= .006, 95% CI, 1.32-4.87). There were no significant differences between the BCG-only group and the IPIOC with BCG group in Grade 3 or more local (16 patients [21%] vs. 21 patients [24%]; P= .61) or systemic (3 patients [4%] vs. 6 patients [7%]; P= .40) toxicity rates. Our study showed the efficacy of IPIOC for the prevention of intravesical recurrence in primary intermediate-risk NMIBC patients regardless of BCG therapy.