scholarly journals Success Rate and Risk Factors Associated with Mini-Implants Reinstalled in the Maxilla

2008 ◽  
Vol 78 (5) ◽  
pp. 895-901 ◽  
Author(s):  
Seung-Hak Baek ◽  
Bo-Mi Kim ◽  
Seung-Hyun Kyung ◽  
Joong Ki Lim ◽  
Young Ho Kim
Keyword(s):  
Success Rate ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Adjacent Area ◽  
Success Rates ◽  
Class Iii ◽  
Mini Implants ◽  
Log Rank Test ◽  
Attached Gingiva

Abstract Objective: To determine the difference in the success rate for two types of oral installed mini-implants (OMIs): one type of initially installed OMI and a new implant of the same type that is reinstalled. Materials and Methods: The subjects consisted of 58 patients (19 male, 39 female; mean age = 21.78 ± 5.85 years) who had received at least one OMI (self-drilling type, conical shape with 2.0-mm upper diameter and 5-mm length) in the attached gingiva of the upper buccal posterior regions for maximum anchorage during en masse retraction. If an OMI failed, a new one was immediately installed in the same area after 4 to 6 weeks or in an adjacent area immediately. The total number of initially installed OMIs (II-OMI) was 109 and the total number of reinstalled OMIs (RI-OMI) was 34. Statistical analysis was performed using χ2 test, Kaplan-Meier method, log-rank test, and Cox proportional hazards regression model. Results: The success rate and mean duration were 75.2% and 10.0 months, respectively, for II-OMI and 66.7% and 6.4 months, respectively, for RI-OMI. Age, vertical skeletal pattern, and site and side of implantation were not related to the success rates of II-OMI and RI-OMI. Log-rank test showed that II-OMI in males and Class III malocclusions were more prone to failure. The relative risk of II-OMI failure in Class III malocclusions as opposed to Class I malocclusions was 5.36 (95% confidence interval, 2.008 to 14.31, P = .001). Conclusion: The success rate of the II-OMI was not statistically different from that of the RI-OMI. Sex and ANB angle might be more important factors for better II-OMI results.

Expression of Epstein-Barr Virus in Cell of Classical Hodgkin's Lymphoma Tumor

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5358-5358
Author(s):  
Abrahão Elias Hallack Neto ◽  
Graziela Toledo Costa Mayrink ◽  
Luciano J. Costa ◽  
Kelli Borges dos Santos
Keyword(s):  
Prognostic Factors ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Chi Square ◽  
Histologic Subtype ◽  
Free Survival ◽  
Barr Virus ◽  
Log Rank Test ◽  
Epstein Barr

Abstract Introduction: The association between classical Hodgkin's Lymphoma (cHL) and tumor Epstein-Barr virus (EBV) status is well established. However, the presence of EBV within Hodgkin/Reed-Sternberg (HRS) cells and its prognosis remains controversial, with conflicting findings from studies of various regions of the world. It is considered essential to deepen the understanding of the pathogenic role of EBV in cHL and its impact in prognosis. Methods: We assessed the correlation between EBV presence in HRS and outcomes in a cohort of Brazilian patients with cHL. EBV positivity was determined by in situ hybridization (ISH) for EBV-encoded RNA (EBER) and immunohistochemistry (IMH) for viral latent membrane protein (LMP-1). All cases were histologically confirmed by an expert hematopathologist who also performed the assays for EBV identification. We examined the prognostic impact of EBV status in 29 patients with cHL. The prognostic factors by IPS (International Prognostic Score) for patients with advanced stage and the risk factors by GHSG (German Hodgkin Study Group) for patients with limited stage were correlated with EBV status tumor cells. For associations between the presence of EBV and other categorical variables, we applied Chi-square or Fisher's exact tests. For describe the effect size (ES) measures for chi-square, we used Cramér's V (V) and odds ratios (OR) with the respective 95% Confidence Intervals (CIs). To evaluate the correlation between all methods of identification of EBV status and among evaluators in histological classification, we applied the Kappa test (K), which measures the degree of agreement these assessments. Differences in OS (overall survival) and EFS (event-free survival) Kaplan-Meier survival curves between EBV-positive and EBV-negative patients were compared statistically using the log-rank test. To evaluate the impact of EBV status on event-free survival controlling for prognostic factors and unfavorable risks, we applied Cox proportional hazards regression to determine hazards ratios (HR) and associated the respective 95% CIs. Multivariate analyses included variables significant at p ≤ 0.15 in univariate models. Results: The mean age at diagnosis was 33 years. Sixty-five percent of the patients had the Nodular Sclerosis histologic subtype and 62,1% had Ann Arbor stage I or II disease at diagnosis. According to GHSG, 88,3% of early-stage patients were classified with unfavorable risk (at least one risk factor) at diagnosis. Compared to advanced-stage patients, 81,9% were considered with favorable IPS (< 4 prognostic factors) at diagnosis. HRS cells were EBV-positive in 37.9% of cases. EBV-positive cHL cases were more frequent in patients ≥ 45 years (71,4% vs. 27,3%, p =0,07). Mixed cellularity (MC) histology subtype was more common in EBV-related tumor cells (p= 0,02) and its effect-size index was medium. The correlation between all methods of identification of EBV status was 96,5% (p< 0,001; K=0.93). The correlation among evaluators in histological classification was 89,6% (p< 0,001; K=0.79). In univariate analysis, age, stage, histologic subtype, nodal involvement, extranodal disease, sex, bulky disease, laboratory data were not associated with adverse EFS (p>0,05). EBV-positive HL seemed to have better EFS than EBV-negative HL (log-rank test, p = 0,07). Cox proportional hazards model confirmed that EBV-positive tumor status and prognosis factors did not impact HL outcome. Conclusions: Despite EBV status in HRS cells not being associated with adverse prognostic factors and not influencing the overall and event-free survivals, the presence of EBV was linked to MC subtype, showing possible implication in histological subtype and worse prognosis. Disclosures Costa: Sanofi: Honoraria, Research Funding.

Pharmacogenetic analysis in metastatic colorectal cancer (mCRC) patients (pts) treated with second-line irinotecan (IR)+/− cetuximab (CB): The EPIC experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4022-4022
Author(s):  
D. Yang ◽  
A. Pohl ◽  
W. Zhang ◽  
G. Lurje ◽  
Y. Ning ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Rank Test ◽  
Second Line ◽  
Ca Repeat ◽  
Ras Mutation ◽  
Mutation Status ◽  
Log Rank Test

4022 Background: EPIC, a multinational phase III clinical trial with IR + CB vs IR alone in mCRC pts in the second-line setting after failure of FOLFOX demonstrated a benefit for IR+CB in progression-free survival (PFS) and response rate (RR). We evaluated functional germline polymorphisms involved in the EGFR- (EGF, EGFR), angiogenesis- (VEGF, IL-8, CXCR-2) - and drug- metabolism related genes (UGT1A1, MTHFR) for their potential role as molecular predictors for clinical outcome in pts treated with CB/IR vs. IR alone. Methods: DNA was extracted from all available formalin-fixed paraffin-embedded tumor samples from the phase III EPIC trial (US sites only). Genotyping was performed using PCR-RFLP assays and 5’ -end [g-33P] ATP’ labeled PCR-protocols. Results: 186 pts were treated either with IR/CB (arm A, 84 pts) or IR (arm B, 102 pts) only. In arm A, 11/84 pts (13%) showed CR or PR, whereas 73/84 (87%) pts had SD or PD. For arm B, 6/102 pts (6%) showed CR or PR, whereas 96/102 pts (94%) had SD or PD. Median PFS in arm A was 3.0 months (95%CI: 2.4- 4.1 months) vs 2.7 months (95%CI: 2.2–2.9 months) in arm B; median overall survival (OS) was 9.3 months (95%CI: 7.1–12.1 months) in arm A vs. 12.3 months (95%CI: 10.4- 17.9 months) in arm B. K-ras mutation status was not significantly associated with PFS or response to CB/IR in the subgroup of 186 patients. We found an EGFR-CA- repeat in intron 1 in arm A to be associated with PFS (p=0.031, log-rank test). In arm B, we found a significant association with RR (p=0.0103, Fisher's exact test) for MTHFR1298. Furthermore, MTHFR 677 (p =0.0048, log-rank test) and MTHFR 1298 (p=0.038, log-rank test) were also found to be associated with OS in arm B. In multivariate analysis, EGFR-CA-repeat was significantly associated with PFS (adjusted p= 0.023). Furthermore, MTHFR 677 and MTHFR 1298 was associated with OS (adjusted p=0.028 and 0.026, respectively, Cox-proportional hazards models), independent from K-ras mutation status, race and number of disease sites. Conclusions: Our study demonstrates the potential predictive value of polymorphisms in the EGFR- and MTHFR- gene in mCRC pts treated with IR+ CB. Further validation in additional clinical trials is necessary. [Table: see text]

Tumor IGF-1 expression as a predictive biomarker for IGF1R-directed therapy in advanced pancreatic cancer (APC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4054-4054 ◽  
Author(s):  
Milind M. Javle ◽  
Rachna T. Shroff ◽  
Gauri R. Varadhachary ◽  
Robert A. Wolff ◽  
David R. Fogelman ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Predictive Biomarker ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Primary Study ◽  
Study Objective ◽  
Log Rank Test ◽  
Hazards Model

4054 Background: IGF-1 up-regulates PC proliferation and invasiveness through activation of PI3K/Akt signaling pathway and down-regulates PTEN. We investigated IGF-1 expression in tissue and blood as potential predictive markers in phase II study of IGF1R-directed monoclonal antibody, MK-0646 in APC. Prior phase I established the MTD of MK0646 at 5 mg/kg with gemcitabine (G) and erlotinib (E) and 10 mg/kg with G alone. Methods: Patients (pts) with stage IV, previously untreated APC, ECOG PS 0-1, adequate hematologic and organ function were enrolled. Arm A: G 1,000 mg/m2 over 100 min, weekly x 3, MK-0646 weekly x 4; Arm B: G 1000 mg/m2 and MK-0646 + E 100 mg daily. Arm C (control) was G 1,000 mg/m2 + E 100 mg. Cycles were repeated every 4 weeks. Pts were equally randomized in the 3 arms. Primary study objective was progression-free survival (PFS). Pre-treatment peripheral blood samples were measured for IGF-1 level by ELISA; archival core biopsies were analyzed for IGF-1 mRNA expression. RNA extraction from FFPE samples used Roche Transcriptor First Strand cDNA Synthesis Kit. TaqMan PreAmp technique was used to amplify target cDNA prior to TaqMan RT-PCR analysis. Cox proportional hazards model for PFS analyzed the interaction between tissue IGF-1 expression and treatment. Results: 50 pts were enrolled (A=15, B=16,C=16 pts, 3 ineligible). Median PFS of arms A, B and C were 5.5 months (95% CI: 3.9 – NA), 3.0 months (95% CI:1.8 – 5.6) and 2.0 months (95% CI: 1.8 – NA), respectively (log-rank test; p = 0.17). Median OS of A was 11.3 months (95% CI: 8.9 – NA), B 8.9 months (95% CI: 5.3 – NA) and C 5.7 months (95% CI: 2.0 – NA) (log-rank test; p = 0.44). 35 archival core biopsies were analyzed, 21 had adequate tissue for analysis. Using a Multivariable Cox proportional hazards model for PFS, where IGF-1 was dichotomized at the median, there was a 76% reduction in the risk of disease progression or death in arm A as compared with the control (arm C) at high IGF-1 level (p = 0.16). When IGF-1 was fitted as a continuous variable, this reduction was 96% (p = 0.08). There was no correlation between tissue and serum IGF-1. Conclusions: Tissue expression of IGF-1 level may represent a promising predictive biomarker for IGF1R-directed therapy in APC.

scholarly journals Progression-Free Survival Prediction in Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy: Machine Learning versus Traditional Statistics

2021 ◽  
Vol 11 (8) ◽  
pp. 787
Author(s):  
Ronald Wihal Oei ◽  
Yingchen Lyu ◽  
Lulu Ye ◽  
Fangfang Kong ◽  
Chengrun Du ◽  
...  
Keyword(s):  
Machine Learning ◽  
Nasopharyngeal Carcinoma ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Brier Score ◽  
Rank Test ◽  
Survival Prediction ◽  
Free Survival ◽  
Log Rank Test

Background: The Cox proportional hazards (CPH) model is the most commonly used statistical method for nasopharyngeal carcinoma (NPC) prognostication. Recently, machine learning (ML) models are increasingly adopted for this purpose. However, only a few studies have compared the performances between CPH and ML models. This study aimed at comparing CPH with two state-of-the-art ML algorithms, namely, conditional survival forest (CSF) and DeepSurv for disease progression prediction in NPC. Methods: From January 2010 to March 2013, 412 eligible NPC patients were reviewed. The entire dataset was split into training cohort and testing cohort in a ratio of 90%:10%. Ten features from patient-related, disease-related, and treatment-related data were used to train the models for progression-free survival (PFS) prediction. The model performance was compared using the concordance index (c-index), Brier score, and log-rank test based on the risk stratification results. Results: DeepSurv (c-index = 0.68, Brier score = 0.13, log-rank test p = 0.02) achieved the best performance compared to CSF (c-index = 0.63, Brier score = 0.14, log-rank test p = 0.38) and CPH (c-index = 0.57, Brier score = 0.15, log-rank test p = 0.81). Conclusions: Both CSF and DeepSurv outperformed CPH in our relatively small dataset. ML-based survival prediction may guide physicians in choosing the most suitable treatment strategy for NPC patients.

scholarly journals Systemic Sclerosis is Linked to Psoriasis and May Impact on Patients’ Survival: A Large Cohort Study

2019 ◽  
Vol 8 (4) ◽  
pp. 521 ◽  
Author(s):  
Watad ◽  
Bragazzi ◽  
McGonagle ◽  
Damiani ◽  
Comaneshter ◽  
...  
Keyword(s):  
Cohort Study ◽  
Systemic Sclerosis ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Medical Database ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Large Cohort Study ◽  
And Gender

Although skin manifestations are quite common in systemic sclerosis (SSc), a link between SSc and psoriasis (PsO) has been poorly investigated. We assessed the Clalit medical database in a cohort study to compare the prevalence of PsO between SSc-patients and SSc-free controls. We also evaluated the SSc-related autoantibodies’ role in the co-existence of the two conditions. Survival analysis was performed using both univariate (Kaplan–Meier, log-rank test) and multivariate (Cox proportional-hazards technique) analyses. Our cohort of 2,431 SSc-patients was age- and gender-matched with 12,710 controls (case-control match 1:5.2). There were 150 (1.2%) cases of PsO among controls and 47 (1.9%) among SSc-patients (p = 0.0027). A SSc diagnosis was an independent risk factor for PsO with an odds ratio (OR) of 2.16 (95%CI 1.38–3.39, p = 0.0008). Among SSc-patients, 98.6% with PsO were antinuclear antibodies (ANA)-negative. In terms of survival, the mortality rate in SSc-patients with PsO was lower than SSc without PsO (14.9% vs. 26%, p < 0.0001). At the multivariate-analysis, SSc-patients with PsO compared to SSc-patients without PsO had an OR for death of 0.44 (95%CI 0.19–0.99, p < 0.05). SSc is independently associated with PsO. The cases with concurrent PsO and SSc are almost exclusively ANA-negative and may exhibit a better survival.

CEA response at four weeks as an early predictor for outcomes in patients (pts) with metastatic colorectal cancer (mCRC) treated with first-line cetuximab-based chemotherapy: A STEP-analysis in the JACCRO CC-05/06 trials.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 543-543 ◽  
Author(s):  
Yu Sunakawa ◽  
Xuemin Fang ◽  
Masahito Kotaka ◽  
Hiroaki Tanioka ◽  
Akinori Takagane ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Phase Ii Trials ◽  
Clinical Biomarkers ◽  
Log Rank Test ◽  
Hazards Model ◽  
Early Tumor

543 Background: We have reported that carcinoembryonic antigen (CEA) response correlated with clinical outcomes of 1st-line cet-based therapy (Target Oncol 2017). Early tumor shrinkage (ETS) is considered to be an on-treatment biomarker for outcomes of chemotherapy; however, clinical biomarkers to predict outcomes earlier are warranted. Methods: This study included 69 pts who were assessable for CEA at baseline and 4 wks, and with observed survival time from 2 phase II trials of 1st-line therapy for KRAS exon2 wild-type mCRC; JACCRO CC-05 of cet plus FOLFOX (UMIN000004197) and CC-06 of cet plus SOX (UMIN000007022). We investigated the influence of baseline age, gender, PS, primary tumor sidedness (PTS), number of tumor sites, as well as the CEA decrease at 4 wks to the patient’s OS and PFS. Results: PTS and the CEA decrease at 4 wks were found to be important predictors to OS and PFS. Baseline CEA and CEA decrease at 4 wks were median of 31.0 (range, 1.0-20920.0) and median of 35% (range, -259%-97%), respectively. The STEP-analysis indicated that CEA response was most significantly associated with OS when a cut-off value of 50% for CEA-responder (HR 0.49, log-rank test p = 0.03). Median OS in responders (n = 25) and non-responders (n = 44) were 36.2 m and 21.5 m, respectively. When the same cut-off value was used, median PFS in responders and non-responders were 11.6 m and 6.5 m, respectively (HR 0.64, log-rank test p = 0.08). In addition, a multivariate Cox Proportional-Hazards Model with both PTS and CEA response as risk factors showed that PTS correlated with both OS and PFS. In pts with left-sided tumors, non-responders (n = 33) had shorter OS and PFS compared to responders (n = 23). In the above 2-covariate Cox proportional hazard model, adjusted HR for CEA 50% decrease is 0.55, p = 0.1; adjusted HR for PTS is 2.66, p = 0.008. Conclusions: Our analysis suggests 50% CEA decrease at 4 wks as an early on-treatment biomarker for 1st-line cet-based therapy in mCRC. It may potentially predict outcomes earlier compared to ETS. Also, CEA response at 4 wks may differentiate pts who receive more benefit from cet treatment in left-sided tumors. Clinical trial information: UMIN000004197 and UMIN000007022.

scholarly journals Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm

2016 ◽  
Vol 124 (1) ◽  
pp. 163-174 ◽  
Author(s):  
Zachary A. Seymour ◽  
Penny K. Sneed ◽  
Nalin Gupta ◽  
Michael T. Lawton ◽  
Annette M. Molinaro ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Radiation Dose ◽  
Arteriovenous Malformations ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Log Rank Test ◽  
Complete Obliteration ◽  
Treatment Volume

OBJECT Large arteriovenous malformations (AVMs) remain difficult to treat, and ideal treatment parameters for volume-staged stereotactic radiosurgery (VS-SRS) are still unknown. The object of this study was to compare VS-SRS treatment outcomes for AVMs larger than 10 ml during 2 eras; Era 1 was 1992-March 2004, and Era 2 was May 2004–2008. In Era 2 the authors prospectively decreased the AVM treatment volume, increased the radiation dose per stage, and shortened the interval between stages. METHODS All cases of VS-SRS treatment for AVM performed at a single institution were retrospectively reviewed. RESULTS Of 69 patients intended for VS-SRS, 63 completed all stages. The median patient age at the first stage of VS-SRS was 34 years (range 9–68 years). The median modified radiosurgery-based AVM score (mRBAS), total AVM volume, and volume per stage in Era 1 versus Era 2 were 3.6 versus 2.7, 27.3 ml versus 18.9 ml, and 15.0 ml versus 6.8 ml, respectively. The median radiation dose per stage was 15.5 Gy in Era 1 and 17.0 Gy in Era 2, and the median clinical follow-up period in living patients was 8.6 years in Era 1 and 4.8 years in Era 2. All outcomes were measured from the first stage of VS-SRS. Near or complete obliteration was more common in Era 2 (log-rank test, p = 0.0003), with 3- and 5-year probabilities of 5% and 21%, respectively, in Era 1 compared with 24% and 68% in Era 2. Radiosurgical dose, AVM volume per stage, total AVM volume, era, compact nidus, Spetzler-Martin grade, and mRBAS were significantly associated with near or complete obliteration on univariate analysis. Dose was a strong predictor of response (Cox proportional hazards, p < 0.001, HR 6.99), with 3- and 5-year probabilities of near or complete obliteration of 5% and 16%, respectively, at a dose < 17 Gy versus 23% and 74% at a dose ≥ 17 Gy. Dose per stage, compact nidus, and total AVM volume remained significant predictors of near or complete obliteration on multivariate analysis. Seventeen patients (25%) had salvage surgery, SRS, and/or embolization. Allowing for salvage therapy, the probability of cure was more common in Era 2 (log-rank test, p = 0.0007) with 5-year probabilities of 0% in Era 1 versus 41% in Era 2. The strong trend toward improved cure in Era 2 persisted on multivariate analysis even when considering mRBAS (Cox proportional hazards, p = 0.055, HR 4.01, 95% CI 0.97–16.59). The complication rate was 29% in Era 1 compared with 13% in Era 2 (Cox proportional hazards, not significant). CONCLUSIONS VS-SRS is an option to obliterate or downsize large AVMs. Decreasing the AVM treatment volume per stage to ≤ 8 ml with this technique allowed a higher dose per fraction and decreased time to response, as well as improved rates of near obliteration and cure without increasing complications. Reducing the volume of these very large lesions can facilitate a surgical approach for cure.

The outcome of patients with stage I endometrial cancer involving the lower uterine segment

2008 ◽  
Vol 18 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
O. Lavie ◽  
L. Uriev ◽  
M. Gdalevich ◽  
F. Barak ◽  
G. Peer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Carcinoma ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Myometrial Invasion ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Stage I ◽  
Rank Test ◽  
Log Rank Test

The objective of this study was to evaluate whether lower uterine segment involvement (LUSI) correlates with recurrence and survival in women with stage I endometrial adenocarcinoma and whether it is associated with poor prognostic histopathologic features. Three hundred seventy-five consecutive patients with endometrial carcinoma stage I compromised the study population. The patients were divided into two groups according to the presence of LUSI with endometrial carcinoma. The two groups were compared with regard to prognostic factors and outcome measures by using the Pearson χ2 test, log-rank test, and Cox proportional hazards model. LUSI was present in 89 (24%) patients with stage I endometrial carcinoma. LUSI was significantly associated with grade 3 tumor (P= 0.022), deep myometrial invasion (P< 0.0001), and the presence of capillary space-like involvement (CSLI) (P= 0.003). Kaplan–Meier survival curves demonstrated that patients with LUSI had a lower recurrence-free survival (log-rank test; P= 0.009) and a worse overall survival (log-rank test; P= 0.0008). In the Cox proportional hazards model, only a trend toward higher recurrence rate (HR = 2.4, 95% CI 0.7, 8.2; P= 0.16) and a trend toward poorer overall survival (HR = 1.54, 95% CI 0.82, 2.91; P= 0.18) were noted when LUSI was present. In patients with stage I endometrial cancer, the presence of LUSI is associated with grade 3 tumor, deep myometrial invasion, and the presence of CSLI. A larger group of patients is necessary to conclude whether higher recurrence rate and poorer overall survival are associated with the presence of LUSI.

scholarly journals Ο ρόλος της λεπτίνης στην επιβίωση των ασθενών με μελάνωμα στον ελληνικό πληθυσμό

2013 ◽  
Author(s):  
Αντώνιος Αντωνιάδης
Keyword(s):  
Insulin Resistance ◽  
Regression Model ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Cox Proportional Hazards Regression ◽  
Log Rank Test ◽  
Proportional Hazards Regression

Η συχνότητα του κακοήθους μελανώματος στον Καυκασιανό πληθυσμό αυξάνεται παγκοσμίως καθιστώντας το μελάνωμα τον πιο γρήγορα αυξανόμενο καρκίνο στο λευκό πληθυσμό, με εξαίρεση τον καρκίνο του πνεύμονα στις γυναίκες264. Η παχυσαρκία αποτελεί παράγοντα κινδύνου για αρκετές μορφές κακοήθειας, ωστόσο η αλληλεπίδραση μελανώματος και παχυσαρκίας δεν έχει μελετηθεί επαρκώς. Ανθρωπομετρικοί παράγοντες, όπως το ύψος, το βάρος και ο δείκτης επιφανείας μάζας σώματος έχουν συσχετιστεί με αυξημένο παράγοντα κινδύνου για αρκετές κακοήθειες συμπεριλαμβανομένου και του μελανώματος66, 204, 213. Η λεπτίνη, μία ορμόνη που εκκρίνεται από το λιπώδη ιστό, ελέγχει την πρόσληψη τροφής και το ενεργειακό ισοζύγιο στέλνοντας σήματα στον υποθάλαμο265. Τα επίπεδα λεπτίνης ορού σχετίζονται θετικά με τη σύνθεση ινσουλίνης και τα επίπεδα ινσουλίνης στο αίμα266. Αυξημένα επίπεδα λεπτίνης ορού έχουν συσχετιστεί με την παχυσαρκία και κάποιους καρκίνους, όπως του μαστού και του ενδομητρίου. Καμία προηγούμενη μελέτη όμως δεν έχει ερευνήσει εάν και κατά πόσο τα επίπεδα λεπτίνης ορού συσχετίζονται με την εμφάνιση, την πρόγνωση και κατ’ επέκταση την επιβίωση στο μελάνωμα. Σύμφωνα με την πρόδρομο μελέτη της ίδιας ερευνητικής ομάδας 83 όπου η λεπτίνη βρέθηκε να συσχετίζεται με αυξημένο κίνδυνο εμφάνισης μελανώματος, αρχικά πραγματοποιήσαμε μια μεταανάλυση για να διερευνήσουμε τη σχέση της παχυσαρκίας με το μελάνωμα56. Έγινε αναζήτηση στις βιβλιογραφικές βάσεις δεδομένων μέχρι τον Οκτώβριο του 2011. Τα αποτελέσματα από τις επιμέρους μελέτες αναλύθηκαν κατά φύλο και οι ομάδες των ατόμων διαχωρίστηκαν σε υπέρβαρους και παχύσαρκους βάσει του BMI και του BSA. Τελικώς συμπεριλήφθησαν 21 άρθρα εκ των οποίων 11 μελέτες ασθενών μαρτύρων και 10 μελέτες παρακολούθησης. Ο εκτιμώμενος σχετικός κίνδυνος ήταν 1.31 (95%CI: 1.18-1.45) για τους υπέρβαρους άντρες και 1.31 (95%CI: 1.19-1.44) αντίστοιχα για τους παχύσαρκους άντρες. Στις γυναίκες τα αποτελέσματα δεν ήταν στατιστικώς σημαντικά [0.98 (95%CI: 0.92-1.05)για τις υπέρβαρες και 0.99 (95%CI: 0.83-1.18) για τις παχύσαρκες]. Τα ευρήματα ήταν αντίστοιχα και όσον αφορά το δείκτη επιφανείας σώματος. Με δεδομένη τη συσχέτιση μεταξύ λεπτίνης, παχυσαρκίας και αντίστασης στην ινσουλίνη και τη πιθανή ογκογενετική τους δράση, στη συνέχεια ερευνήσαμε το αν η αντίσταση στην ινσουλίνη σχετίζεται με αυξημένο κίνδυνο εμφάνισης μελανώματος85. Έγινε προσδιορισμός του δείκτη Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), της λεπτίνης και της αδιπονεκτίνης ορού σε 55 ασθενείς με μελάνωμα και 165 υγιείς μάρτυρες τυχαιοποιημένους ανά ηλικία και φύλο κατά ζεύγη. Ο σχετικός κίνδυνος για τη νόσο προσδιορίστηκε μετά από έλεγχο σε μια σειρά από μεταβλητές-συγχυτικούς παράγοντες που περιελάμβαναν τον τύπο δέρματος, τα κοινωνικά-δημογραφικά στοιχεία και ανθρωπομετρικούς δείκτες. Η μέση τιμή του HOMA-IR ήταν σχεδόν 1,5 φορές υψηλότερη στους ασθενείς σε σύγκριση με τους υγιείς μάρτυρες. Στην ομάδα ελέγχου ο δείκτης HOMA-IR συσχετίστηκε θετικώς με το ΒΜΙ (r=0.34; p=0.0001), το WHR (r=0.20; p=0.01), αρνητικά με την αδιπονεκτίνη ορού (r=-0.21; p=0.006) και καθόλου με τη λεπτίνη ορού. (0.09; p=0.27). Στη λογαριθμική ανάλυση παλινδρόμησης το HOMA-IR εμφάνισε συσχέτιση με αυξημένο κίνδυνο εμφάνισης μελανώματος και ο κίνδυνος αυξανόταν με την αύξηση των επιπέδων της αντίστασης στην ινσουλίνη (σχετικός κίνδυνος 5ης εκατοστιαίας θέσης =3,75). Η συσχέτιση παρέμεινε ακόμη και μετά την ενσωμάτωση και των άλλων μεταβλητών που ελέγχθηκαν. Ο συνυπολογισμός της αδιπονεκτίνης δεν τροποποίησε τα αποτελέσματα, ενώ η προσθήκη της λεπτίνης στην ανάλυση καθιστούσε τα αποτελέσματα μη στατιστικώς σημαντικά. Επίσης μελετήσαμε τη συσχέτιση της λεπτίνης με την επιβίωση των ασθενών από τη νόσο. Μέχρι σήμερα δεν υπάρχουν βιβλιογραφικές αναφορές σε σχέση με το θέμα αυτό και η έρευνα αυτή είναι πρόδρομη, αν και σε μικρό αριθμό ασθενών. Συγκεκριμένα ελέγχθηκαν 150 ασθενείς με μελάνωμα ηλικίας από 23 έως 88 ετών, οι οποίοι προσήλθαν στο εξωτερικό ογκολογικό ιατρείο του ΓΝ Λαϊκό κατά τη χρονική περίοδο από το Νοέμβριο του 2007 έως τον Μάρτιο του 2009. Οι συμμετέχοντες υποβλήθηκαν ακολούθως σε συνέντευξη με ειδικό προτυπωμένο ερωτηματολόγιο από τον υποψήφιο διδάκτορα. Παράλληλα με τη καταγραφή πληροφοριών αναφορικά με το ιατρικό ιστορικό, τους ανθρωπομετρικούς δείκτες, την έκθεση στην ηλιακή ακτινοβολία και τις διαιτητικές συνήθειες, έγινε και λήψη αίματος για τον προσδιορισμό της λεπτίνης και ινσουλίνης ορού. Τα στοιχεία σχετικά με την επιβίωση των ασθενών κατεγράφησαν από την εποπτεύουσα κα Γκόγκα σε συνεργασία με τον υποψήφιο διδάκτορα μέχρι τον Δεκέμβριο του 2012. Οι μονοπαραγοντικές κατανομές της έκβασης (εν ζωή ή νεκρός) για τους ασθενείς της μελέτης μας μελετήθηκαν στη συνέχεια με τη χρήση του log-rank test. Η επίδραση όλων των ρυθμισμένων μεταβλητών στην επιβίωση από τη νόσο μελετήθηκε στη συνέχεια με τη χρήση του μοντέλου Cox proportional hazards regression model. Τα αποτελέσματα κατέδειξαν ελαττωμένη πιθανότητα επιβίωσης για ασθενείς με προχωρημένη νόσο, μεγάλη ηλικία και ιστολογικό τύπο νόσου που δεν ανήκε στην κατηγορία του επιφανειακώς εξαπλούμενου μελανώματος. Οι παχύσαρκοι άντρες εμφάνισαν μια στατιστικώς σημαντική πιθανότητα μεγαλύτερης επιβίωσης σε σχέση με πιο αδύνατους άντρες ασθενείς, (HR= 0.47, p=0.006), ενώ οι παχύσαρκες γυναίκες ασθενείς είχαν χειρότερη επιβίωση χωρίς όμως να εμφανίζεται στατιστική σημαντικότητα στην ανάλυση. Μεγαλύτερη πιθανότητα θανάτου ήταν επίσης εμφανής σε καπνιστές ή τέως καπνιστές άντρες (HR=2.19) και σε ασθενείς με πιο σκουρόχρωμο δέρμα. Η προσθήκη της λεπτίνης και /ή της ινσουλίνης στο βασικό μοντέλο δεν τροποποίησε τα αποτελέσματα.Η παρούσα διδακτορική διατριβή μελέτησε το ρόλο της λεπτίνης ,της παχυσαρκίας και της αντίστασης στην ινσουλίνη στον κίνδυνο εμφάνισης και την επιβίωση σε ασθενείς με μελάνωμα στον ελληνικό πληθυσμό. Τα ευρήματα υποδεικνύουν ότι η παχυσαρκία αποτελεί προδιαθεσικό παράγοντα κινδύνου για μελάνωμα στο άρρεν φύλο, ενώ και η αντίσταση στην ινσουλίνη φαίνεται να σχετίζεται με αυξημένο κίνδυνο εμφάνισης της νόσου. Η λεπτίνη πιθανώς να αποτελεί ένα συνδετικό κρίκο σε αυτή τη επάλληλη σχέση, αλλά δεν φάνηκε να σχετίζεται με την επιβίωση από το μελάνωμα.

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