The role of apoptosis in colorectal carcinogenesis and its prognostic value.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22131-e22131
Author(s):  
Julia Alcaide ◽  
Rafael Funez ◽  
Antonio Rueda ◽  
Elisabeth Pérez-Ruiz ◽  
Teresa Pereda ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Proportional Hazards ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Colorectal Carcinogenesis ◽  
Categorical Variables ◽  
Rank Test ◽  
Continuous Variables ◽  
Normal Epithelium

e22131 Background: Most colorectal cancers (CRCs) progress through a multistep process from normal tissue to adenoma to carcinoma. The role of apoptosis during this tumourigenesis sequence has not yet been completely clarified. The aim of our study was to determine the influence of apoptotic variations on the carcinogenesis and prognosis of CRC. Methods: A TUNEL assay was performed on the formalin-fixed, paraffin-embedded tissues from 103 CRCs resected at the Costa del Sol Hospital (after excluding patients previously treated with chemotherapy or radiation therapy), 26 adenomas and 20 samples of normal epithelia. Clinical data were obtained from the tumour registry and hospital charts. The study was approved by Research Ethics Committee. We used the median (m) of apoptotic percentage (1%, range: 0-6%) as a threshold value for survival (sv) studies. Analysis of association between apoptosis and prognostic factors used the X2test for categorical variables and the analysis of variance test for continuous variables (natural log transformed if necessary). We estimated sv using the Kaplan-Meier method, and sv curves were compared with the log rank test. Cox’s proportional hazards sv analysis was used to determine the relative risk (RR) through multivariate analyses. Results: Median follow-up was 50 months (mo). Apoptotic index (AI) was higher in CRCs (1.09 ± 0.13) than in adenomas (0.38 ± 0.23, p=0.059) and significantly greater than in normal epithelium (0.06 ± 0.04, p=0.001). AI was greater in stage IV than in other stages (p=0.017). Higher AI was associated with lower disease-free survival (DFS) and overall survival (OS) than lower AI (Table). In multivariate analysis, AI (RR=2.18, 95% CI 1.08-4.37) and TNM stage (RR=2.41, 95% CI 1.20-4.85) were independent prognostic factors for OS. Conclusions: Our study demonstrates an increase in apoptosis during colorectal carcinogenesis and a correlation between apoptotic rates and survival. Higher AIs are associated with more aggressive tumours and a poorer prognosis in CRC. [Table: see text]

scholarly journals Epilepsy as a Comorbidity in Polymyositis and Dermatomyositis—A Cross-Sectional Study

2021 ◽  
Vol 18 (8) ◽  
pp. 3983
Author(s):  
Ella Nissan ◽  
Abdulla Watad ◽  
Arnon D. Cohen ◽  
Kassem Sharif ◽  
Johnatan Nissan ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cross Sectional Study ◽  
Cox Proportional Hazards ◽  
Categorical Variables ◽  
Rank Test ◽  
Control Group ◽  
Multivariable Logistic Regression Analysis ◽  
Positive Trend ◽  
Continuous Variables ◽  
Cross Sectional

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case–control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student’s t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan–Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy (n = 48 [2.3%]) as compared to controls (n = 141 [1.4%], p < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], p = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], p = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.

The Clinical Role of Micrornas (miRs) in Cytogenetically Normal (CN) Acute Myeloid Leukemia (AML): miR-155 Upregulation Independently Identifies High-Risk Patients (Pts)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1387-1387 ◽  
Author(s):  
Guido Marcucci ◽  
Kati Maharry ◽  
Klaus H. Metzeler ◽  
Stefano Volinia ◽  
Yue-Zhong Wu ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Conflicts Of Interest ◽  
Disease Free Survival ◽  
Gene Expression Signature ◽  
White Blood Count ◽  
Categorical Variables ◽  
Prognostic Impact ◽  
Continuous Variables ◽  
Wild Type

Abstract Abstract 1387 miR-155 is upregulated in aggressive subtypes of solid tumors and leukemia. In AML, higher miR-155 expression is associated with FLT3-ITD. However, whether miR-155 upregulation impacts on clinical outcome independently from FLT3-ITD and other prognosticators is unknown. We evaluated the prognostic impact of miR-155 in 363 CN-AML pts (153 age <60 y; 210 age ≥60 y) that were treated with cytarabine-daunorubicin-based regimens and had a median follow-up of 7.9 y (range, 2.3–12.9). miR-155 levels were measured in pretreatment marrow or blood by the NanoString nCounter assay quantifying expression of the encoding gene MIR155HG; other molecular markers were assessed centrally. High miR-155 expressers (miR-155) had higher WBC (P<.001) and were more often FLT3-ITD-positive (pos; P<.001), RUNX1-mutated (mut; <.001), WT1-mut (P=.03), ↑ ERG (P=.02) and ↑ BAALC (P=.002), and less often CEBPA-mut (P=.003), IDH2-mut (P=.004) and FLT3-TKD-pos (P=.08) than low expressers (↓ miR-155). ↑ miR-155 had lower CR rates (P<.001), shorter DFS (P=.001) and OS (P<.001), than ↓ miR-155. In multivariable analyses (MVA; Table), ↑ miR-155 was associated with lower CR rates (P=.007) and shorter OS (P<.001). Among younger pts, ↑ miR-155 had lower CR rates (P=.03) and shorter DFS (P<.001) and OS (P<.001) than ↓ miR-155. In MVA (Table), ↑ miR-155 status remained associated with worse CR rate (P=.06), shorter DFS (P=.003) and OS (P=.01). Among older pts, ↑ miR-155 had lower CR rates (P=.008) and shorter OS (P<.001); in MVA (Table), ↑ miR-155 remained associated with worse CR (P=.03) and shorter OS (P=.05). In the European LeukemiaNet classification, younger ↑ miR-155 in the Favorable (Fav) Genetic Group (GG; CEBPA-mut and/or NPM1-mut without FLT3-ITD) had lower CR rates (P=.03) and shorter DFS (P=.04) and OS (P=.02) than ↓ miR-155. In the younger Intermediate-I (Int-I) GG pts (with wild-type CEBPA, NPM1-mut with FLT3-ITD, or wild-type NPM1), miR-155 expression did not impact independently on outcome. In older pts, ↑ miR-155 had a shorter OS both in the Fav (P=.06) and Int-I GGs (P=.05) than ↓ miR-155. To gain biologic insights, we derived an Affymetrix gene-expression signature that comprised 196 mRNAs significantly correlated with miR-155 expression. Consistent with previous mechanistic studies, Gene Ontology analysis revealed that the ↑ miR-155-associated signature was enriched for genes involved in anti-apoptotic, proliferative and inflammatory activities (FDR<0.05). ↑ miR-155 was not significantly correlated with that of any other microRNAs (miRs) thereby supporting the unique role of miR-155 among the miRs in AML. In summary, miR-155 expression is independently associated with clinical outcome in CN-AML and may allow for better evaluation of molecular risk, especially in pts lacking FLT3-ITD, like those in the ELN Fav GG. Moreover, given its role in deregulation of fundamental mechanisms of cell homeostasis and the emergence of miR inhibitors, miR-155 may become a novel therapeutic target. Table. MVA in pts with primary CN-AML Group CR DFS OS OR P HR P HR P All pts miR-155 expression not significantly associated with DFS a     miR-155, ↑ v ↓ 0.46 .007 1.62 <.001     NPM1, mut v wt 2.42 .005     BAALC, ↑ v ↓ 0.37 .002 2.16 <.001     WBC, each 50 units 0.65 <.001     Age group, older v younger 0.43 .003 2.38 <.001     FLT3-ITD, pos v neg 1.78 <.001     Race, white v nonwhite 1.62 .03 Pts age < 60 y     miR-155, ↑ v ↓ 0.39 .06 2.13 .003 1.84 .01     RUNX1, mut v wt 0.21 .01     Age, each 10 y increase 0.45 .004     WBC, each 50 units 1.49 <.001     FLT3-ITD, pos v neg 2.82 <.001 1.82 .01     FLT3-TKD, pos v neg 3.27 <.001     BAALC, ↑ v ↓ 2.66 <.001 2.33 <.001     Race, white v nonwhite 2.81 .02     CEBPA, mut v wt 0.47 .02     WT1, mut v wt 2.25 .005 Pts age ≥ 60 y miR-155 expression not significantly associated with DFS     miR-155, ↑ v ↓ 0.46 .03 1.36 .05     NPM1, mut v wt 2.45 .03     BAALC, ↑ v ↓ 0.32 .004 2.18 <.001     WBC, each 50 units 0.65 .005     Age, each 10 y increase 0.48 .02     FLT3-ITD, pos v neg 1.56 .006 ↑, high expression; ↓, low expression; CR, complete remission; DFS, disease-free survival; HR, hazard ratio; mut, mutated; neg, negative; OR, odds ratio; OS, overall survival; pos, positive; WBC, white blood count; wt, wild-type. Odds ratios > (<) 1.0 mean higher (lower) CR rate and HRs > (<) 1.0 mean higher (lower) risk of relapse or death (DFS) or death (OS) for the higher values of continuous variables and the 1st category listed for categorical variables. Disclosures: No relevant conflicts of interest to declare.

The association between immune-related adverse events and efficacy outcomes with consolidation pembrolizumab after chemoradiation in patients with stage III NSCLC: an analysis from HCRN LUN 14-179.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9032-9032
Author(s):  
Nikhil Shukla ◽  
Sandra K. Althouse ◽  
Ahad Ali Sadiq ◽  
Shadia Ibrahim Jalal ◽  
Salma K. Jabbour ◽  
...  
Keyword(s):  
Adverse Events ◽  
Stage Iv ◽  
Wilcoxon Test ◽  
Stage Iii ◽  
Categorical Variables ◽  
Rank Test ◽  
Continuous Variables ◽  
Current Standard ◽  
Group A ◽  
Stage Iii Nsclc

9032 Background: Consolidation checkpoint inhibitor therapy (CPI) for up to 1 year following chemoradiation (CRT) is a current standard of care for pts with inoperable stage III NSCLC. However, some pts are not able to complete 1 year of CPI due to immune-related adverse events (irAES). In multiple retrospective studies, pts with stage IV NSCLC treated with CPI who experience irAEs generally receive fewer cycles of CPI without a significant detrimental effect on efficacy. The association between irAEs and outcomes with consolidation CPI after CRT has never been reported. Here we report the association between irAEs and efficacy outcomes from the HCRN LUN 14-179, a single-arm phase II trial of consolidation pembrolizumab following concurrent CRT in pts with unresectable stage III NSCLC. Methods: After completion of CRT eligible pts with stage III NSCLC without PD received pembrolizumab 200 mg IV q 3 wks for up to 1 yr. Demographics, disease characteristics, and number of cycles of pembrolizumab received were reported in pts who had any grade irAEs (except pneumonitis which included grade >2 only) [Group A] and those without irAEs (except grade 1 pneumonitis) [Group B]. Chi-square test (or Fisher's Exact test) were used for comparisons for categorical variables and Wilcoxon test for continuous variables. The Kaplan-Meier method was used to analyze time to metastatic disease (TMDD), PFS, and OS. A log-rank test was used to compare groups. Results: 92 eligible pts for efficacy analysis were enrolled from March 2015 to November 2016. 4 yr OS estimate for all pts is 46.2%. Any grade irAEs (except grade I pneumonitis) (n = 37 pts) included pneumonitis (18.5%), colitis (3.3%), increased creatinine (5.4%), elevated transaminases (3.3%), hyperthyroidism (7.6%), hypothyroidism (13.0%). Grade ≥ 2 irAEs (n = 32 pts) included pneumonitis (18.5%), hypothyroidism (10.8%), and colitis (3.3%). Group A/B: male (21/38), female (16/17), current or former smoker (35/52), stage IIIA (20/35), stage IIIB (17/20), non-squamous (21/30), squamous (16/25). Median number of pembrolizumab cycles received in Group A/B pts were 9 vs 15 (p = 0.0942) respectively. 4 yr efficacy endpoints in Groups A/B were TMDD 35.3% vs 41.3% (p = 0.83), PFS 27.8% vs 28.7% (p = 0.97), OS 43.5% vs 47.9% (p = 0.99), respectively. Conclusions: Despite receiving fewer cycles of consolidation pembrolizumab, pts who experienced any grade irAEs (excluding grade 1 pneumonitis) did not have significantly reduced efficacy outcomes. Clinical trial information: NCT02343952.

scholarly journals Therapeutic Role of Retroperitoneal Lymphadenectomy in 170 Patients With Ovarian Clear Cell Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Wen Gao ◽  
Peipei Shi ◽  
Haiyan Sun ◽  
Meili Xi ◽  
Wenbin Tang ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Proportional Hazards ◽  
Clear Cell ◽  
Cell Cancer ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Advanced Stage ◽  
Therapeutic Role ◽  
Retroperitoneal Lymphadenectomy

IntroductionWe evaluated the therapeutic role of retroperitoneal lymphadenectomy in patients with ovarian clear cell cancer (OCCC).Materials and MethodsWe retrospectively reviewed 170 OCCC patients diagnosed at two hospitals in China between April 2010 and August 2020. Clinical data were abstracted, and patients were followed until February 2021. Patients were divided into retroperitoneal lymphadenectomy and no lymphadenectomy groups. The Kaplan–Meier method was used to compare progression-free (PFS) and overall survival (OS) between the two groups. Statistical differences were determined by the log-rank test. The COX proportional hazards regression model was applied to identify predictors of tumor recurrence.ResultsThe median age was 52 years; 90 (52.9%) and 80 (47.1%) patients were diagnosed as early and advanced stage, respectively. Clinically positive and negative nodes was found in 40 (23.5%) and 119 (70.0%) patients, respectively. Of all the 170 patients, 124 (72.9%) patients underwent retroperitoneal lymphadenectomy, while 46 (27.1%) did not. The estimated 2-year PFS and 5-year OS rates were 71.4% and 65.9% in the lymphadenectomy group, and 72.0% and 73.7% in no lymphadenectomy group (p = 0.566 and 0.669, respectively). There was also no difference in survival between the two groups when subgroup analysis was performed stratified by early and advanced stage, or in patients with clinically negative nodes. Multivariate analysis showed that retroperitoneal lymphadenectomy were not an independent predictor of tumor recurrence.ConclusionRetroperitoneal lymphadenectomy provided no survival benefit in patients diagnosed with OCCC. A prospective clinical trial is needed to confirm the present results.

RADT-33. LONG-TERM OUTCOMES, TREATMENT UTILIZATION, AND PROGNOSTIC FACTORS FOR PEDIATRIC CHORDOMA: AN NCDB ANALYSIS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi48-vi48
Author(s):  
James Cantrell ◽  
Pawan Acharya ◽  
Sara Vesely ◽  
Michael Confer ◽  
Ozer Algan ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Radiation Dose ◽  
Proportional Hazards ◽  
Propensity Score Analysis ◽  
Descriptive Analysis ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Total Resection ◽  
Kaplan Meier

Abstract BACKGROUND Chordomas are rare tumors arising from the embryonal notochord presenting at the base of skull, spine, or sacrum. Pediatric chordomas (PC) comprise less than 5% of all chordomas and are more likely to be atypical or dedifferentiated. Evidence for management is limited to single institution series with 5-year overall survival (OS) between 60-100%. METHODS Using the NCDB Participant User File, a retrospective observational cohort study was performed. The cohort was defined using the bone-soft-tissue, brain, and central nervous system databases selecting for cases with chordoma ICD-03 codes and age ≤ 25 years. Kaplan Meier method, log-rank test, and Cox proportional hazards regression were performed. RESULTS 297 patients from 2004-2017 met inclusion criteria for descriptive analysis with 269 cases included for survival analysis. Mean age was 16.9 years, with 10% less than age 5. The cohort was 55% female, 8% Black, and 79% White. Primary sites included bones of the skull (70%), spine (22%), and pelvis (6%). Regarding treatment, 7% had no resection, 49% sub-total resection (STR), 33% gross-total resection (GTR), and 11% unspecified resection. 51% received radiation therapy with 46% of those receiving proton therapy. 7% received chemotherapy. The 1, 3, 5, and 10-year OS was 95%, 86%, 77%, and 72%. Selected prognostic factors from univariable OS model for OS analysis included: age &gt; 5 (HR 0.30 (95% CI 0.16-0.57) p = 0.0002), surgical resection [GTR (HR 0.28 (95% CI 0.12-0.63) p = 0.0023) and STR (HR 0.27 (95% CI 0.12-0.59) p = 0.0011)], and radiation dose ≥ 7200cGy (HR 0.40 (95% CI 0.16-0.99) p = 0.047). CONCLUSION In the largest cohort reported for PC, 3 and 10-year OS was 86% and 72%. Age, surgery, and radiation dose are important prognostic factors. Propensity score analysis to gauge effect of treatment, tumor, and patient characteristics on OS is forthcoming.

scholarly journals The Role of Vitamin D Receptor Gene Polymorphisms in Colorectal Cancer Risk

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1379
Author(s):  
Ippokratis Messaritakis ◽  
Asimina Koulouridi ◽  
Maria Sfakianaki ◽  
Konstantinos Vogiatzoglou ◽  
Nikolaos Gouvas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Bacillus Stearothermophilus ◽  
Receptor Gene ◽  
Stage Iv ◽  
Colorectal Carcinogenesis ◽  
Thermus Aquaticus ◽  
Vdr Gene

Vitamin D deficiency has been associated with increased colorectal cancer (CRC) incidence risk and mortality. Vitamin D mediates its action through the binding of the vitamin D receptor (VDR), and polymorphisms of the VDR might explain these inverse associations. The aim of the study was the investigation of the relevance of rs731236; Thermus aquaticus I (TaqI), rs7975232; Acetobacter pasteurianus sub. pasteurianus I (ApaI), rs2228570; Flavobacterium okeanokoites I (FokI) and rs1544410, Bacillus stearothermophilus I (BsmI) polymorphisms of the VDR gene to colorectal carcinogenesis (CRC) and progression. Peripheral blood was obtained from 397 patients with early operable stage II/III (n = 202) and stage IV (n = 195) CRC. Moreover, samples from 100 healthy donors and 40 patients with adenomatous polyps were also included as control groups. Genotyping in the samples from patients and controls was performed using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP). A significant association was revealed between all four polymorphisms and cancer. Individuals with homozygous mutant (tt, aa, ff or bb) genotypes were more susceptible to the disease (p < 0.001). All of the mutant genotypes detected were also significantly associated with stage IV (p < 0.001), leading to significantly decreased survival (p < 0.001). Moreover, all four polymorphisms were significantly associated with KRAS (Kirsten ras oncogene) mutations and Toll-like receptor (TLR2, TLR4 and TLR9) genetic variants. In multivariate analysis, tt, aa and ff genotypes emerged as independent factors associated with decreased overall survival (OS) (p = 0.001, p < 0.001 and p = 0.001, respectively). The detection of higher frequencies of the VDR polymorphisms in CRC patients highlights the role of these polymorphisms in cancer development and progression.

Stage IV marginal zone B-cell lymphoma - prognostic factors and the role of rituximab: Consortium for Improving Survival of Lymphoma (CISL) study

2010 ◽  
Vol 101 (11) ◽  
pp. 2443-2447 ◽  
Author(s):  
Sung Yong Oh ◽  
Won Seog Kim ◽  
Jin Seok Kim ◽  
Seok Jin Kim ◽  
Suee Lee ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
B Cell Lymphoma

How Informed is “Informed Consent” for Robotic Cardiothoracic Surgery?

2009 ◽  
Vol 4 (6) ◽  
pp. 307-310 ◽  
Author(s):  
Sean Ryan ◽  
Vasu Chirumamilla ◽  
Ricardo A. Bello ◽  
David A. D'Alessandro ◽  
Robert E. Michler ◽  
...  
Keyword(s):  
Informed Consent ◽  
Patient Education ◽  
Cardiothoracic Surgery ◽  
Categorical Variables ◽  
Socioeconomic Background ◽  
Continuous Variables ◽  
Robotic Assisted ◽  
Education Of Patients ◽  
Invasive Techniques

Objective The education of patients in the informed consent process remains a challenge for many surgeons. In cardiothoracic surgery, emerging minimally invasive techniques including robotics add another level of complexity to the patient education process. We sought to evaluate our patients’ perceptions and informed knowledge after robotic-assisted cardiothoracic surgery. Methods A survey containing questions designed to elicit patients’ perceptions about robotic cardiothoracic surgery was given postoperatively by telephone 1 month to 12 months after surgery. The survey included questions about the type of procedure, function of the organ operated on, purpose of the operation, primary “surgeon” (robot vs. human), patients’ opinion about robotic-assisted surgery, educational level, and socioeconomic background. Continuous variables are reported as mean ± SD. Continuous and categorical variables were compared using the Student t test and Pearson χ2 test, respectively. Ordinal variables were compared using the Mann-Whitney U test. P values of <0.05 were considered significant. Results Between 2002 and 2007, 198 patients underwent robotic cardiothoracic surgery. One hundred fifty patients (76%) were contacted and 89 (45%) fully completed the survey. Of the respondents, there were 31 coronary artery bypasses, 33 pacemaker lead implantations, esophageal resections, 8 thymectomies, and 9 others. The mean age of the patients was 61.1 ± 15 years (range, 23–87) and there were 52 men (58.4%). A total of 96.6% of patients were satisfied with the information provided by the surgeon and 92.1% felt that they understood the information. The diagnosis, target organ, and procedure were correctly identified by 81 (91.0%), 83 (93.3%), and 76 (85.4%) of the patients, respectively. A total of 80 (89.9%) knew a robot was involved and 73.8% understood the role of the robot in the surgery. These results were independent of age, income, and education level achieved. Conclusions Overall, patients demonstrated an understanding of the role of the robot in their cardiothoracic surgery. Despite the increasing complexity of robotics, preoperative patient education can result in patients who are both satisfied and well educated about their cardiothoracic surgery procedures.

scholarly journals Predictors of survival after surgery with curative intent for perihilar cholangiocarcinoma

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Joachim Geers ◽  
Joris Jaekers ◽  
Halit Topal ◽  
Raymond Aerts ◽  
Cindy Vandoren ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Caudate Lobe ◽  
Perihilar Cholangiocarcinoma ◽  
Rank Test ◽  
Curative Surgery ◽  
Curative Intent ◽  
Term Survival ◽  
Physical Status Classification

Abstract Background Several clinicopathological predictors of survival after curative surgery for perihilar cholangiocarcinoma (pCCA) have been identified; however, conflicting reports remain. The aim was to analyse clinical and oncological outcomes after curative resection of pCCA and to determine prognostic factors. Methods Eighty-eight consecutive patients with pCCA underwent surgery with curative intent between 1998 and 2017. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Twenty-one prognostic factors were evaluated using multivariate Cox regression models. Results Postoperative complications were observed in 73 (83%) patients of which 41 (47%) were severe complications (therapy-oriented severity grading system (TOSGS) grade > 2), including a 90-day mortality of 9% (n = 8). Overall survival (OS) and disease-free survival (DFS) rates at 5 and 10 years after surgery were 33% and 19%, and 37% and 30%, respectively. Independent predictors of OS were locoregional lymph node metastasis (LNM) (risk ratio (RR) 2.12, confidence interval (CI) 1.19–3.81, p = 0.011), patient American Society of Anesthesiologists (ASA) physical status classification system > 2 (RR 2.10, CI 1.03–4.26, p = 0.043), and depth of tumour penetration (pT) > 2 (RR 2.58, CI 1.03–6.30, p = 0.043). The presence of locoregional LNM (RR 2.95, CI 1.51–5.90, p = 0.002) and caudate lobe resection (RR 2.19, CI 1.01–5.14, p = 0.048) were found as independent predictors of DFS. Conclusions Curative surgery for pCCA carries high risks with poor long-term survival. Locoregional LNM was the only predictor for both OS and DFS.

Pharmacogenetics of Tamoxifen Biotransformation Is Associated With Clinical Outcomes of Efficacy and Hot Flashes

2005 ◽  
Vol 23 (36) ◽  
pp. 9312-9318 ◽  
Author(s):  
Matthew P. Goetz ◽  
James M. Rae ◽  
Vera J. Suman ◽  
Stephanie L. Safgren ◽  
Matthew M. Ames ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Hot Flashes ◽  
Disease Free Survival ◽  
Metabolic Activation ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Buccal Cells ◽  
Cancer Trial ◽  
Adjuvant Breast Cancer

Purpose Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown. Methods We determined cytochrome P450 (CYP)2D6 (*4 and *6) and CYP3A5 (*3) genotype from paraffin-embedded tumor samples and buccal cells (living patients) in tamoxifen-treated women enrolled onto a North Central Cancer Treatment Group adjuvant breast cancer trial. The relationship between genotype and disease outcome was determined using the log-rank test and Cox proportional hazards modeling. Results Paraffin blocks were obtained from 223 of 256 eligible patients, and buccal cells were obtained from 17 living women. CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determined from 190, 194, and 205 patient samples and in 17 living women. The concordance rate between buccal and tumor genotype was 100%. Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-time; P = .023) and disease-free survival (DFS; P = .012), but not overall survival (P = .169) and did not experience moderate to severe hot flashes relative to women heterozygous or homozygous for the wild-type allele. In the multivariate analysis, women with the CYP2D6 *4/*4 genotype still tended to have worse RFS (hazard ratio [HR], 1.85; P = .176) and DFS (HR, 1.86; P = .089). The CYP3A5*3 variant was not associated with any of these clinical outcomes. Conclusion In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen.

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