Advanced Stage Group Research Articles

Artificial Intelligence Based on Blood Biomarkers Including CTCs Predicts Outcomes in Epithelial Ovarian Cancer: A Prospective Study.

ObjectiveWe aimed to develop an ovarian cancer-specific predictive framework for clinical use platinum-sensitivity and prognosis using machine learning methods based on multiple biomarkers, including circulating tumor cells (CTCs).Patients and MethodsWe enrolled 156 epithelial ovarian cancer (EOC) patients, randomly assigned into the training and validation cohorts. Eight machine learning classifiers, including Random Forest (RF), Support Vector Machine, Gradient Boosting Machine, Conditional RF, Neural Network, Naive Bayes, Elastic Net, and Logistic Regression, were used to derive predictive information from 11 peripheral blood parameters, including CTCs. Through the advanced CanPatrol CTC-enrichment technique, we detect CTCs and classify them into subpopulations: epithelial, mesenchymal, and hybrids. Survival curves were generated by Kaplan–Meier method and calculated through the Log rank test.ResultsMachine learning techniques, especially the Random Forest classifier, were superior to conventional regression-based analyses in predicting multiple clinical parameters related to EOC. The values for the receiver operating characteristic (ROC) curve for segregating EOC with advanced clinical stages and platinum-sensitivity were 0.796 (95% CI, 0.727–0.866) and 0.809 (95% CI, 0.742–0.876), respectively. Stepwise, we used the unsupervised clustering analysis to identify EOC subgroups with significantly worse overall survival (OS), especially in the advanced-stage group with the p-value of 0.0018 (HR, 2.716; 95% CI, 1.602–4.605) for progression-free survival (PFS) and 0.0037 (HR, 2.359; 95% CI, 1.752–6.390) for overall survival (OS).ConclusionMachine learning systems could provide risk stratification for EOC patients before initial intervention through blood variables, including circulating tumor cells. The predictive algorithms could facilitate personalized treatment options through promising pre-treatment stratification of EOC patients.Trial registrationChiCTR-DDD-16009601 Registered 25 October 2016.

Intraperitoneal Glucose Transport to Micrometastasis: A Multimodal In Vivo Imaging Investigation in a Mouse Lymphoma Model.

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes. We aimed to investigate its early stage spread at one day post-intraperitoneal inoculation of lymphoma cells (n = 18 mice), and its advanced stage at seven days post-inoculation with in vivo [18F]FDG-PET and [18F]PET/MRI, and ex vivo by autoradiography and Cherenkov luminescence imaging (CLI). Of the early stage group, nine animals received intraperitoneal injections, and nine received intravenous [18F]FDG injections. The advanced stage group (n = 3) received intravenous FDG injections. In the early stage, using autoradiography we observed a marked accumulation in the mesentery after intraperitoneal FDG injection. Using other imaging methods and autoradiography, following the intravenous injection of FDG no accumulations were detected. At the advanced stage, tracer accumulation was clearly detected in mesenteric lymph nodes and in the peritoneum after intravenous administration using PET. We confirmed the results with immunohistochemistry. Our results in this model highlight the importance of local FDG administration during diagnostic imaging to precisely assess early peritoneal manifestations of other malignancies (colon, stomach, ovary). These findings also support the importance of applying topical therapies, in addition to systemic treatments in peritoneal cancer spread.

Primary cutaneous T-cell lymphomas in childhood and adolescence.

Primary cutaneous lymphomas are extranodal non-Hodgkin lymphomas of T- or B- cell origin, that predominantly affect older patients but have been reported in all age groups and as early as in the first years of life. Diagnosis of cutaneous lymphomas is challenging and requires high clinical suspicion and close collaboration between dermatologists, pediatric oncologists and pathologists. Skin involvement of non-Hodgkin lymphomas in children or adolescents can either be primary cutaneous or secondary due to an underlying nodal lymphoma. The most common primary cutaneous lymphomas encountered in children are of T-cell origin, with mycosis fungoides being the most prevalent cutaneous T-cell lymphoma, followed by CD30+ lymphoproliferative disorders. While cutaneous lymphomas share clinicopathologic characteristics between juvenile and adult forms, there are important differences in terms of clinical presentation, diagnosis and treatment. The hypopigmented variant of mycosis fungoides seems to be overrepresented in the pediatric age group. Prognosis and treatment of mycosis fungoides are stage dependent. The majority of children present with early-stage disease and respond well to topical corticosteroids and phototherapy.

Does Time-to-Chemotherapy after Primary Complete Macroscopic Cytoreductive Surgery Influence Prognosis for Patients with Epithelial Ovarian Cancer? A Study of the FRANCOGYN Group.

To determine if the time-to-chemotherapy (TTC) after primary macroscopic complete cytoreductive surgery (CRS) influences recurrence-free survival (RFS) and overall survival (OS) in patients with epithelial ovarian cancer (EOC). We conducted an observational multicenter retrospective cohort analysis of women with EOC treated from September 2006 to November 2016 in nine institutions in France (FRANCOGYN research group) with maintained EOC databases. We included women with EOC (all FIGO stages) who underwent primary complete macroscopic CRS prior to platinum-based adjuvant chemotherapy. Two hundred thirty-three patients were included: 73 (31.3%) in the early-stage group (ESG) (FIGO I-II), and 160 (68.7%) in the advanced-stage group (ASG) (FIGO III-IV). Median TTC was 43 days (36–56). The median OS was 77.2 months (65.9–106.6). OS was lower in the ASG when TTC exceeded 8 weeks (70.5 vs. 59.3 months, p = 0.04). No impact on OS was found when TTC was below or above 6 weeks (78.5 and 66.8 months, respectively, p = 0.25). In the whole population, TTC had no impact on RFS or OS. None of the factors studied were associated with an increase in TTC. Chemotherapy should be initiated as soon as possible after CRS. A TTC greater than 8 weeks is associated with poorer OS in patients with advanced stage EOC.

Hospital competition, quality, and cost of prostate cancer care.

235 Background: Hospital competition is important for addressing the disparity in quality and cost of prostate cancer care. Study objective was to examine the association of hospital competition with process of care (time to treatment, treatment and overuse) and outcomes (medial care use, complications, mortality and cost) in Medicare fee-for-service beneficiaries with prostate cancer. Methods: This was a population-based cohort study of Surveillance, Epidemiological, and End Results-Medicare (SEER-Medicare) data from 1995- 2016, linked with American Medical Association for physician data and American Hospital Association for hospital level data. Eligible patients were men 66 years or older with localized or advanced stage prostate cancer at diagnosis. The Hirschman-Herfindahl index (HHI) was computed for all serving hospitals based on number of competitors, i.e., number of hospitals situated within the hospital referral region(HRR). The Overuse Index (OI) was used to composite measure of overuse during treatment (one year after diagnosis) and follow-up care phase. Outcomes were overall and prostate cancer-specific survival, complications, readmissions, ER visits, and cost. We used survival analysis, including competing risk analysis, Poisson (zero inflated) models for count data, and GLM (log-link) models for cost data. Propensity score and instrumental variable approaches were used to minimize potential biases. Results: In our study cohort of 434,264, 85% of patients had localized disease stage, and 15% had advanced stage. For both localized and advanced stage groups, age, race and ethnicity, geographic region, comorbidity, socio-economic status, and primary treatment differed by hospital competition (high competition vs. low competition). Hospitals within high competition area were more likely to perform surgery, whereas hospitals within low competition area were more likely to perform radiation therapy. Among localized disease patients, low hospital competition was associated with higher hazard of overall mortality (HR = 1.08, 95% CI = 1.07 - 1.10) and prostate cancer-specific mortality (HR = 1.13, 95% CI = 1.09 - 1.17) and higher odds of ER visits (OR = 1.13, 95% CI = 1.11 - 1.15). For advanced stage patients, low hospital competition was associated with higher hazard of overall mortality (HR = 1.11, 95% CI = 1.08 - 1.15) and prostate cancer-specific death (HR = 1.15, 95% CI = 1.09 - 1.18) and higher odds of ER visits (OR = 1.16, 95% CI = 1.11 - 1.22). Higher scores of the OI were associated with higher total medical costs per capita per year, and not associated with overall mortality. Conclusions: This novel study showed that higher hospital competition is associated with improved quality of care (reduced mortality, complications and ER visits) and increased/lower direct medical care cost among patients with localized or advanced stage prostate cancer. Policy measures should be implemented to improve hospital competition.

Sodium [18F]Fluoride PET Can Efficiently Monitor In Vivo Atherosclerotic Plaque Calcification Progression and Treatment.

Given the high sensitivity and specificity of sodium [18F]Fluoride (Na[18F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[18F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE−/− mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet. The Menaquinone-7 (MK-7) and Warfarin groups received MK-7 or Warfarin supplementation during the additional 12-weeks, respectively. Control wild type mice were fed a chow diet for 24-weeks. All of the mice were scanned with Na[18F]F using a small animal positron emission tomography (PET)/computed tomography (CT). The Warfarin group presented spotty calcifications on the CT in the proximal aorta. All of the spots corresponded to dense mineralisations on the von Kossa staining. After the control, the MK-7 group had the lowest Na[18F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[18F]F uptake was still observed, suggesting the presence of micro-calcifications. In a newly applied mouse model, developing spotty calcifications on CT exclusively in the proximal aorta, Na[18F]F seems to efficiently monitor plaque progression and the beneficial effects of vitamin K on cardiovascular disease.

Involvement of Oral Microbiota in the Gut Microbiota of Colorectal Cancer

Background: The oral microbiota is reportedly associated with the gut microbiota and influences colorectal cancer (CRC) progression; however, the details remain unclear. Methods: This study included 52 patients diagnosed with CRC and 51 healthy controls. Saliva and stool samples were collected, and microbiota were evaluated using 16S rRNA analysis and next-generation sequencing. Comparative analysis was performed on both groups. Findings: Linear discriminant analysis Effect Size (LEfSe) revealed indigenous oral bacteria, such as Peptostreptococcus, Streptococcus, and Solobacterium spp., were present at a significantly higher relative abundance in CRC patients compared with controls, consistent for both saliva and stool. LEfSe was also performed after the CRC patients were divided into early stage (Stage I, II; n = 26; 50%) and advanced stage (Stage III, IV; n = 26;, 50%) disease. S. moorei was present at a significantly higher relative abundance in the advanced-stage group compared with the early-stage group, again consistent for both saliva and stool. Interpretation: Among the bacterial species whose relative abundance was significantly higher in CRC patients, P. stomatis, S. anginosus, S. koreensis and S. moorei were apparently supplied from the oral cavity, suggesting indigenous oral bacteria may have promoted initiation of CRC carcinogenesis. Furthermore, S. moorei may influence CRC progression. Funding Statement: This research was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (19K10361)(15H05045). Declaration of Interests: All authors declare no interests. Ethics Approval Statement: The study was conducted in accordance with the “Declaration of Helsinki.” The study protocols were approved by the ethics committee of Kagoshima University. Informed consent was obtained from all the study participants.

A Urine Metabonomics Study of Rat Bladder Cancer by Combining Gas Chromatography-Mass Spectrometry with Random Forest Algorithm

A urine metabolomics study based on gas chromatography-mass spectrometry (GC-MS) and multivariate statistical analysis was applied to distinguish rat bladder cancer. Urine samples with different stages were collected from animal models, i.e., the early stage, medium stage, and advanced stage of the bladder cancer model group and healthy group. After resolving urea with urease, the urine samples were extracted with methanol and, then, derived with N, O-Bis(trimethylsilyl) trifluoroacetamide and trimethylchlorosilane (BSTFA + TMCS, 99 : 1, v/v), before analyzed by GC-MS. Three classification models, i.e., healthy control vs. early- and middle-stage groups, healthy control vs. advanced-stage group, and early- and middle-stage groups vs. advanced-stage group, were established to analyze these experimental data by using Random Forests (RF) algorithm, respectively. The classification results showed that combining random forest algorithm with metabolites characters, the differences caused by the progress of disease could be effectively exhibited. Our results showed that glyceric acid, 2, 3-dihydroxybutanoic acid, N-(oxohexyl)-glycine, and D-turanose had higher contributions in classification of different groups. The pathway analysis results showed that these metabolites had relationships with starch and sucrose, glycine, serine, threonine, and galactose metabolism. Our study results suggested that urine metabolomics was an effective approach for disease diagnosis.

Synchronous Primary Endometrial and Ovarian Cancers: Trends and Outcomes of the Rare Disease at a South Asian Tertiary Care Cancer Center.

Background and objectiveThe incidence of synchronous primary endometrial and ovarian cancer is uncommon and poses a diagnostic challenge to the treating physician about their origin as either primary or metastasis. The purpose of this study was to evaluate the clinicopathological behavior, treatment modality-related outcomes, and prognosis related to primary endometrial and ovarian cancers at a tertiary care referral center in South Asia.MethodsWe retrospectively analyzed 30 patients with synchronous ovarian and endometrial cancers treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre in Lahore, Pakistan from January 2005 to August 2017.ResultsThe median age of the patients at the time of diagnosis was 51 years (range: 25-72 years). The common presenting symptoms were irregular uterine bleeding (30%), post-menopausal bleeding (26.7%), abdominal mass (16.7%), and abdominal pain (26.7%). Endometrial adenocarcinoma type was the most common histological variant found among the participants: 90% (n=27) of uterine and 56.7% (n=17) of ovarian cancers. All patients underwent surgical intervention. Among them, 25 patients received platinum-based adjuvant chemotherapy, four received neoadjuvant chemotherapy, and 18 received adjuvant radiotherapy. The early-stage group [International Federation of Gynecology and Obstetrics (FIGO) stage I and II] had a more favorable prognosis than the advanced stage group (FIGO stages III and IV).ConclusionBased on our findings, patients with synchronous primary endometrial and ovarian cancers have better overall survival rates than patients with single primary ovarian or endometrial cancers. Also, synchronous primary endometrial and ovarian cancer endometroid types have better overall survival than patients with non-endometrioid or mixed histologic types.

Patient Characteristics and Outcomes of Nonmetastatic Breast Cancer in Haiti: Results from a Retrospective Cohort.

BackgroundThere are few studies on breast cancer outcomes in the Caribbean region. This study identified a retrospective cohort of female patients with nonmetastatic breast cancer in Haiti and conducted survival analyses to identify prognostic factors that may affect patient outcomes.MethodsThe cohort included 341 patients presenting between June 2012 and December 2016. The primary endpoint was event‐free survival (EFS), defined as time to disease progression, recurrence, or death. Descriptive summaries of patient characteristics and treatments were reported. Survival curves were plotted using Kaplan‐Meier estimation. Multivariate survival analyses were performed using Cox proportional hazards regression.ResultsMedian age at diagnosis was 49 years, with 64.2% being premenopausal. Most patients (55.1%) were staged as locally advanced. One hundred and sixty patients received neoadjuvant therapy: 33.3% of patients with early stage disease and 61.2% of those with locally advanced stage disease. Curative‐intent surgery was performed in 278 (81.5%) patients, and 225 patients received adjuvant therapy. Adjuvant endocrine therapy was used in 82.0% of patients with estrogen receptor–positive disease. During the follow‐up period, 28 patients died, 77 had disease recurrence, and 10 had progressive disease. EFS rates at 2 years and 3 years were 80.9% and 63.4%, respectively. After controlling for multiple confounders, the locally advanced stage group had a statistically significant adjusted hazard ratio for EFS of 3.27 compared with early stage.ConclusionPatients with nonmetastatic breast cancer in Haiti have more advanced disease, poorer prognostic factors, and worse outcomes compared with patients in high‐income countries. Despite several limitations, curative treatment is possible in Haiti.Implications for PracticePatients with breast cancer in Haiti have poor outcomes. Prior studies show that most Haitian patients are diagnosed at later stages. However, there are no rigorous studies describing how late‐stage diagnosis and other prognostic factors affect outcomes in this population. This study presents a detailed analysis of survival outcomes and assessment of prognostic factors in patients with nonmetastatic breast cancer treated in Haiti. In addition to late‐stage diagnosis, other unfavorable prognostic factors identified were young age and estrogen receptor‐negative disease. The study also highlights that the availability of basic breast cancer treatment in Haiti can lead to promising early patient outcomes.

Treatment Outcomes for Primary Retromolar Trigone Carcinoma: A Single Institution Experience.

Retromolar trigone (RMT) is a rare location for oral cavity cancers. RMT cancers are aggressive malignancies that mostly present at an advanced stage. In this study, we aimed to evaluate treatment outcomes in patients who underwent initial radical surgical resection and postoperative radiotherapy or chemoradiotherapy with a diagnosis of primary RMT squamous cell carcinoma in our institution. The study included 20 primary RMT tumor patients out of 191 oral cavity cancer cases treated from January 2010 through December 2019. We retrospectively analyzed treatment details, histopathology reports, postoperative clinical course and survival outcomes. The mean age at presentation was 59.4 years. Eighty percent of all patients were either stage 3 or stage 4. We performed mandibular resection in 14 patients (70%) and partial maxillectomy in eight patients (40%). Nineteen patients (95%) underwent unilateral neck dissection. The incidence of metastatic cervical lymph node was 13/20 (65%). Overall survival (OS) and disease-free survival (DFS) rates during follow-up (mean 26.3 months) were 60% and 75%, respectively. There was statistical significance between presence of multilevel metastatic lymph nodes and OS (p=0.013). DFS and OS of early stage and advanced stage groups were 100% vs 75% and 100% vs 50%, respectively, with no statistical significance (p=0.189 and p=0.084). The survival of advanced stage RMT cancer is poor despite appropriate treatment. Bone involvement that necessitates resection is common due to the proximity of the tumor to the mandible and the maxilla. Multilevel positive cervical lymph nodes and advanced stage are poor prognostic factors.

Treatment and outcome of patients with uterine carcinosarcoma: Data from developing world.

e18102 Background: To evaluate the clinicopathological factors, outcome and prognostics factors of uterine carcinosarcoma. Methods: All patients of uterine carcinosarcoma treated between January 2013 and December 2018 were identified and their clinical, laboratory and imaging details were retrieved from electronic medical record. Details of the treatment received, toxicity profile and outcome were recorded and analyzed. Patients (including stage I) were considered for four cycles of chemotherapy (Paclitaxel +Carboplatin) followed by radiation (EBRT to pelvis with vaginal brachytherapy). Survival analysis was done using the Kaplan–Meier method and compared between treatment groups using the Log-rank test. Results: Of 81 cases, 48 % presented with early stage disease (FIGOI-II) and 52 % with late stage (FIGO III-IV) disease. Median age was 58 years (30-80 years). Most women (83%) were postmenopausal and 80% of them presented with postmenopausal bleeding. Six patients developed carcinosarcoma on adjuvant tamoxifen (given for breast cancer) after a median drug intake of 8 years. In early stage, 10% patients received only surgical treatment; 46% received both chemotherapy (CT) and radiation therapy (RT) while 33 % received RT alone. In advanced stage, 31% received only CT, 14 % received only RT and 33% received both CT and RT after surgery. About 8% of patients had myelosuppression(grade I/II), 10 % had peripheral neuropathy (grade I/II) and 11% had electrolyte imbalance. At a median follow up of 2 years (1- 80 months), median DFS and OS in early stage group was 28.5 months and 31.0 months while in advanced stage group it was 13.0 months and 15.0 months respectively. Distant metastasis (omentum, peritoneum and lung being the common site) were seen in 30% of patients while local relapse was seen in 5 % cases. On univariate analysis stage of disease and receipt of adjuvant therapy were the factors found to be significantly associated with improved OS (p < 0.001) and adjuvant RT alone was associated with improved DFS (p < 0.023). Conclusions: Adjuvant treatment (chemotherapy and or radiation therapy) is associated with improved overall survival in uterine carcinosarcoma, irrespective of stage at presentation.

Application of the amide proton transfer-weighted imaging and diffusion kurtosis imaging in the study of cervical cancer.

To analyze the value of amide proton transfer-weighted imaging (APTWI) and diffusion kurtosis imaging (DKI) in differentiating cervical cancer (CC) pathological type, grade, and stage. One hundred and twelve women underwent pelvic APTWI and DKI. The magnetization transfer ratio asymmetry (MTRasym, 3.5ppm), apparent kurtosis coefficient (Kapp), and non-Gaussian diffusion coefficient (Dapp) were calculated by histological subtype, grade, and stage. The differences, efficacy, and correlation between parameters were determined. The MTRasym(3.5ppm) and Dapp values of the adenocarcinoma (CA) group were higher than those of the cervical squamous carcinoma (CSC) group, while the Kapp values were lower than those of the CSC group. The MTRasym(3.5ppm) and Kapp values of the high-grade group were higher than those of the low-grade group, while the Dapp values were lower than those of the low-grade group. The Dapp values of the advanced-stage group were lower than those of the early-stage group, while the Kapp values were greater than those of the early-stage group. The Kapp showed the highest efficacy in differentiating CSC and CA, high- and low-grade CC, and advanced- and early-stage CC. In the CSC and CA groups, both the Kapp and Dapp were highly correlated with pathological grade, and the MTRasym(3.5ppm) was weakly correlated with pathological grade. The Kapp, Dapp, and MTRasym(3.5ppm) were all weakly correlated with pathological stage. Both DKI and APTWI can be used in preliminary evaluations of CC, but DKI has advantages in the identification of pathological type, grade, and stage. • PTWI and DKI provide new information regarding cervical cancer. • MTRasym(3.5ppm), Dapp, and Kapp are valid parameters to characterize tissue microstructure. • DKI is superior to APTWI in the study of cervical cancer.

Is remnant pancreatic cancer after pancreatic resection more frequent in early-stage pancreatic cancer than in advanced-stage cancer?

AimAs the prognosis of patients who undergo resection for pancreatic cancer has improved, reports of remnant pancreatic cancer after pancreatic cancer resection have been increasing. Previous studies regarding early‐stage pancreatic cancer showed a high incidence of remnant pancreatic cancer in these patients. The aim of this study was to investigate the incidence of remnant pancreatic cancer according to the degree of progression of the initial pancreatic cancer.MethodsPatients who underwent partial pancreatic resection for primary pancreatic cancer were retrospectively reviewed and divided into an early‐stage group and an advanced‐stage group according to the stage of the initial cancer. Patient characteristics and long‐term outcomes, including development of remnant pancreatic cancer, were compared between the two groups.ResultsThis study included 321 patients who underwent partial pancreatectomy for pancreatic cancer; 32 patients in the early‐stage group and 289 patients in the advanced‐stage group. Remnant pancreatic cancer developed in 19 patients (5.9%); seven patients (21.9%) in the early‐stage group and 12 patients (4.5%) in the advanced‐stage group. The cumulative incidence of remnant pancreatic cancer according to the Kaplan–Meier method was comparable between the two groups (5‐year cumulative incidence: 20.6% vs 9.9%, early‐stage group vs advanced‐stage group; P = .1827).ConclusionOur results suggested that the potential for developing remnant pancreatic cancer was comparable between the early‐stage and the advanced‐stage groups. Therefore, the incidence of remnant pancreatic cancer may increase along with improved pancreatic cancer treatment.

Value of High-Frequency Ultrasound in Accurate Staging of Mycosis Fungoides/Sézary Syndrome.

This study was aimed to assess the ultrasound (US) characteristics of mycosis fungoides (MF)/Sézary syndrome (SS) and explore the value of high-frequency US in accuracy staging for classic mycosis fungoides (cMF). A prospective study was designed. Twenty-six patients with histopathologically confirmed MF or SS were enrolled to undergo HF-US examinations. Both 50- and 20-MHz US images of the most prominent lesion of each patient were collected by a cutaneous diagnostic US system, and the US characteristics in different stages were analyzed by 2 physicians independently. The Fisher exact test was used for the statistical analysis. A total of 26 patients underwent this study, including 23 with cMF, 2 with folliculotropic mycosis fungoides (FMF), and 1 with SS. Among cMF, 16 patients with patches or plaques (the early-stage group) showed a subepidermal low-echogenic band, and only 3 lesions in the plaque stage partially extended to the superficial dermis. Seven patients with tumors (the advanced-stage group) showed lesions that infiltrated to the deep dermis or subcutaneous tissue. The infiltration depth (P < .001), clarity of the boundary (P = .002), and homogeneity of internal echoes (P = .001) were significantly different between the early and advanced stages. Additionally, the 2 FMF lesions and 1 SS lesion had characteristic manifestations, showing a well-defined subepidermal low-echogenic band with patchy hypoechoic regions around the hair follicles in the dermis. High-frequency US can be used to accurately detect the infiltration depth and morphologic features of MF/SS lesions and provide important information for tumor staging of cMF. Additionally, the characteristic US features in FMF and SS might be helpful for diagnosis.

Integrated Plasma and Neuroimaging Biomarkers Associated with Motor and Cognition Severity in Parkinson's Disease.

Easily accessible biomarkers are crucial for disease-modifying clinical trials in patients with Parkinson's disease (PD). We investigated integrated plasma and neuroimaging biomarkers correlating with motor and cognitive severity in PD patients. This cross-sectional study enrolled 170 participants (12 controls and 158 PD patients). Plasma α-synuclein and neurofilament light chain (NfL) level, and global and regional cortical thickness (CTh) on brain MRI were analyzed to predict advanced motor stage (Hoehn & Yahr stage ≥3), and PD dementia (PDD, MMSE score <26). Plasma α-synuclein and NfL levels were higher in PD patients than controls (both P < 0.0001 for α-synuclein and NfL). Plasma NfL levels were significantly elevated in patients with advanced motor stage (P = 0.008) or PDD; α-synuclein was elevated in the advanced motor stage group. Global CTh was thinner in patients with PDD than controls (2.33±0.19 mm vs 2.43±0.14 mm, P = 0.06). Among PD patients, higher α-synuclein was associated with thinner limbic CTh, whereas higher NfL was associated with thinner temporal CTh and insular CTh. The accuracy of predicting advanced motor stage using age and sex alone (area under the curve [AUC] 0.63) was significantly improved by the addition of plasma α-synuclein and NfL, and temporal and insula CTh (full model, AUC 0.77, P = 0.004). The accuracy of predicting PDD using age and sex alone (AUC 0.82) increased by incorporating plasma α-synuclein and NfL, and temporal and insula CTh as full model (AUC 0.87, P = 0.047). Integrated plasma and neuroimaging biomarkers reflect both motor and cognitive aspects of PD severity.

Detection of Plasma Circulating Tumor DNA in Ovarian Cancer and Its Clinical Significance

To explore the application value of circulating tumor DNA in the diagnosis of benign and malignant ovarian tumors and its clinical significance in ovarian malignant tumors. A total of 70 patients with ovarian tumors who treated surgery in the first people’s hospital of Lianyungang and the affiliated cancer hospital of Nanjing medical university from January 2017 to August 2020 were collected, including 32 cases of benign tumors, 15 cases of cross-sectional tumors, and 23 cases of malignant tumors. Venous blood was collected before the operation, and the expression level of the plasma circulating tumor DNA was detected by Next-Generation Sequencing, and the expression of circulating tumor DNA chromosome copy number variation in benign and malignant ovarian tumors was analyzed. At the same time, the relationship between the preoperative plasma circulating tumor DNA and clinicopathological features such as tumor size, clinical stage, histological grade, pathological type, and related immunohistochemical indexes were analyzed. There was a significant difference in preoperative plasma circulating tumor DNA among patients with benign, cross-sectional, and malignant tumors of the ovary (p<0.05). In terms of the clinical stage, there were 9 cases in the early stage group (I+II), 5 (55.56 %) cases were positive for plasma circulating tumor DNA before the operation. In the advanced stage group (III+IV), there were 14 cases, 12 (85.71 %) cases were positive for plasma circulating tumor DNA before the operation. In the histological grade of malignant ovarian cancer, there were 6 cases of ovarian low-grade cancer, of which 3 (50.0 %) cases were positive for plasma circulating tumor DNA before the operation. There were 17 cases of ovarian high-grade cancer, of which 14 (82.35 %) cases were positive for plasma circulating tumor DNA before the operation. Among the pathological types of tumors, there were 16 cases of plasma carcinoma and 14 (87.5 %) cases were positive for plasma circulating tumor DNA. There were 7 cases of non-plasma carcinoma and 3 (42.85 %) cases were positive for plasma circulating tumor DNA. In terms of tumor size, there were 7 cases with a diameter <10cm, of which 3 (42.85 %) cases were circulating tumor DNA positive. There were 16 cases of tumor diameter ≥10 cm, of which 14 (87.5 %) cases were circulating tumor DNA positive. In terms of pathological immunohistochemistry, among the 17 ovarian cancer patients with positive preoperative plasma circulating tumor DNA, there were 14 (82.35 %) patients with p53 mutation, and 3 (17.65 %) negative patients. There was no significant difference between the detection rate of plasma circulating tumor DNA and the immunohistochemical indexes such as Ki67, P16, estrogen receptor, progesterone receptor, and Wilms tumor protein-1 before the operation. Circulating tumor DNA level has a high predictive value for the disease progression in patients with ovarian cancer, and can be used as a reference index for clinical monitoring of patients’ condition and prognosis.

Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG).

Almost one-third of all patients with chronic lymphocytic leukemia (CLL) express stereotyped B-cell receptor immunoglobulins (BcR IG) and can be assigned to distinct subsets, each with a particular BcR IG. The largest stereotyped subsets are #1, #2, #4 and #8, associated with specific clinico-biological characteristics and outcomes in retrospective studies. We assessed the associations and prognostic value of these BcR IG in prospective multicenter clinical trials reflective of two different clinical situations: (i) early-stage patients ('watch and wait' arm of the CLL1 trial) (n=592); (ii) patients in need of treatment, enrolled in three phase III trials (CLL8, CLL10, CLL11), treated with different chemo-immunotherapies (n=1,861). Subset #1 was associated with del(11q), higher CLL International Prognostic Index (CLL-IPI) scores and similar clinical course to CLL with unmutated immunoglobulin heavy variable (IGHV) genes (U-CLL) in both early and advanced stage groups. IGHV-mutated (M-CLL) subset #2 cases had shorter time-to-first-treatment (TTFT) versus other M-CLL cases in the early-stage cohort (hazard ratio [HR]: 4.2, confidence interval [CI]: 2-8.6, P<0.001), and shorter time-to-next-treatment (TTNT) in the advancedstage cohort (HR: 2, CI: 1.2-3.3, P=0.005). M-CLL subset #4 was associated with lower CLL-IPI scores and younger age at diagnosis; in both cohorts, these patients showed a trend towards better outcomes versus other MCLL. U-CLL subset #8 was associated with trisomy 12. Overall, this study shows that major stereotyped subsets have distinctive characteristics. For the first time in prospective multicenter clinical trials, subset #2 appeared as an independent prognostic factor for earlier TTFT and TTNT and should be proposed for risk stratification of patients. (Trials registered at clinical trials. gov identifiers: NCT00262782, NCT00281918, NCT2000769522, and NCT01010061).

ACTIVITY OF SUPEROXIDE DISMUTASE ENZYME IN EARLY AND ADVANCED STAGES OF NASOPHARYNGEAL CARCINOMA

Introduction:Nasopharyngeal cancer (NPC) ranks - fourth among all cancers in Indonesia.&#x0D; Objective:This study aimed to determine the levels of SOD in patients with NPC.&#x0D; Material and methods : This was a cross sectional study of analytic observational, using consecutive sampling, with 45 patients with NPC and 15 controls.&#x0D; Results: Average of SOD enzyme levels were higher in the NPC patient group (± 1877.87224 1137.119495) compared with the control group (± 441.42120 320.355669) (p &lt;0.05). SOD enzyme levels were higher in advanced stage ± 2060.67363 1179.147923 compared with early stage ± 1338.86685 680.958439 (p &lt;0.05).&#x0D; Conclusion: The level of SOD enzyme in patients with nasopharyngeal cancer is higher than in the control group, and the level is higher in the advanced stage group than in the early stage group.

Mitochondria-related reversal of early-stage diabetic nephropathy in donor kidney after transplantation in mice.

Renal diabetic changes are frequent in kidney transplantation (KTx) donors. Whether these diabetic changes are reversible remains a topic of debate. This study aimed to test the hypothesized reversibility of diabetic changes after KTx. C57BL/6J mice were randomly divided into three groups: the control group, early-stage group (ESG), and advanced-stage group (ASG). Diabetes mellitus (DM) was induced in mice by intraperitoneal injection of streptozotocin (STZ) at 50 mg/kg body weight for five consecutive days. Blood glucose levels ≥16.7 mmol/L were indicative of diabetic mice. The kidneys from ESG and ASG were transplanted to control mice 12 or 32 weeks after STZ injection. Kidney tissue, blood, and 24-hour urine specimens of donor and recipient mice were collected before KTx and 28 days after KTx, respectively. We measured the body weight, blood glucose, histological changes, reactive oxygen species (ROS), apoptosis. Electron microscopy was also performed to evaluate the mitochondrial morphology. The expression of NADPH oxidases (NOXs) was assessed by qRT-PCR. Kidneys from early-stage diabetic mice showed evidence of lesion reversal four weeks after KTx, including decreased urinary albumin and reversal of histological changes. Besides, mitochondrial swelling, oxidative stress, apoptosis, and overexpression of NOXs in the kidneys were also suppressed. Conversely, no changes were observed in kidneys from advanced-stage diabetic mice after KTx. We confirmed that early-stage but not advanced-stage diabetic nephropathy (DN) is reversible, which is related to reduced NOX expression and improvement in mitochondrial function. These results indicated that kidneys with early-stage DN could be used for KTx in clinical practice, as the disease may be reversed following KTx.