Extramural Venous Invasion as Prognostic Factor of Recurrence in Stage 1 and 2 Colon Cancer

Aim. Extramural venous invasion (EMVI) is a prognostic indicator in patients with colorectal cancer. However, its additional value in patients with stage 1 and 2 colorectal cancer is uncertain. In the present study, the incidence of EMVI and the hazard ratio for recurrence in patients with stage 1 and 2 colon cancer were studied. Methods. 184 patients treated for stage 1 and 2 colon cancer were included with a follow-up of at least 5 years. Chart review was performed and EMVI was assessed by two separate pathologists. EMVI was scored with additional caldesmon staining on the resection specimen. Primary outcomes were recurrence-free survival (RFS) measured through the Cox regression analysis and prevalence of EMVI. Results. There were 10 cases of EMVI and 3 cases of intramural venous invasion (IMVI) all occurring in patients with stage 2 disease corresponding to a prevalence of 9%. Thirty-one percent of the patients with venous invasion experienced recurrence versus 14% in patients without, corresponding with a hazard ratio of 2.39 (p=0.11). Conclusion. The present study demonstrates a trend towards an increased risk of recurrence in patients with stage 2 colon cancer with venous invasion. This warrants consideration of adjuvant chemotherapy despite the lack of lymph node metastases.

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Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

Frontiers in Pediatrics ◽

10.3389/fped.2021.714406 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yen-Chu Huang ◽

Meng-Che Wu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Research Database ◽

Real World Data ◽

Childhood Disorders ◽

Cox Regression Analysis ◽

Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

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Clinicopathological and molecular differences in colorectal cancer according to location

The International Journal of Biological Markers ◽

10.1177/1724600818807164 ◽

2019 ◽

Vol 34 (1) ◽

pp. 47-53 ◽

Cited By ~ 5

Author(s):

Yu-Lun Hsu ◽

Chun-Chi Lin ◽

Jeng-Kai Jiang ◽

Hung-Hsin Lin ◽

Yuan-Tzu Lan ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Overall Survival ◽

Cox Regression ◽

Rank Test ◽

Advanced Tumor Stage ◽

Tumor Seeding ◽

Cox Regression Analysis ◽

Advanced Tumor ◽

Tumor Node Metastasis Stage

Purpose: The incidence, pathogenesis, molecular pathways, and outcomes of colorectal cancer vary depending on the location of the tumor. This study aimed to compare the difference in tumor characteristics and the outcome between right-sided colon cancer and left-sided colorectal cancer (LCRC). Materials and methods: A total of 1503 patients with colorectal cancer who underwent surgery at the Taipei Veterans General Hospital between 2000 and 2010 were enrolled in this study. Right-sided colon cancer was defined as cancers in the cecum, ascending colon, and transverse colon, while LCRC was defined as cancers in the splenic flexure colon, descending colon, sigmoid colon, and rectum. The endpoint was overall survival. The mutations were detected via polymerase chain reaction and MASS array. The prognostic value was determined using the log-rank test and the Cox regression analysis. Results: A total of 407 and 1096 cases were classified as right-sided colon cancer and LCRC, respectively. Compared to patients with LCRC, those with right-sided colon cancer had more mucinous type cancer (7.4% vs. 3.5%), poorly differentiated tumor (11.5% vs. 3.6%), and advanced tumor-node-metastasis stage. The risk for peritoneal tumor seeding was higher in the right-sided colon cancer group (12.8% vs. 5.7%). Overall survival was better in LCRC than in right-sided colon cancer ( P=0.036). Conclusions: In our study, right-sided colon cancer had a more advanced tumor stage, a higher risk of peritoneal metastasis, and a poorer outcome than LCRC. Moreover, right-sided colon cancer had more gene mutations in BRAF, KRAS, SMAD4, TGF-β, PIK3CA, PTEN, AKT1, and high microsatellite instability.

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Factors Affecting Successful Localization of the Central Sulcus Using the Somatosensory Evoked Potential Phase Reversal Technique

Neurosurgery ◽

10.1227/neu.0b013e3182897447 ◽

2013 ◽

Vol 72 (5) ◽

pp. 828-834 ◽

Cited By ~ 8

Author(s):

Sameer A. Sheth ◽

Christine A. Eckhardt ◽

Brian P. Walcott ◽

Emad N. Eskandar ◽

Mirela V. Simon

Keyword(s):

Evoked Potential ◽

Cox Regression ◽

Hazard Ratio ◽

Somatosensory Evoked Potential ◽

Central Sulcus ◽

Cox Regression Analysis ◽

Phase Reversal ◽

Increased Risk ◽

Postcentral Gyrus ◽

Time Required

Abstract BACKGROUND: Perirolandic surgery is associated with an increased risk of postoperative neurological deficit that can be reduced by accurate recognition of the location of sensorimotor cortex. The median somatosensory evoked potential (MSSEP) phase reversal technique (PRT) reliably identifies the central sulcus (CS) intraoperatively, but does require additional surgical time. Awareness of factors that lengthen the time required for MSSEP PRT has important implications for surgical planning. OBJECTIVE: To identify factors that affect the time required for CS localization via MSSEP PRT. METHODS: Multivariate Cox regression analysis, applied in 100 consecutive cases of perirolandic surgery at a single institution from 2005 to 2010, during which CS localization was attempted via a standardized MSSEP PRT. RESULTS: The CS was reliably identified in 77 cases. The mean time to identification was 5 minutes (SD = 5; range, 1–20 minutes). Lesion location either very close to the CS (within the postcentral gyrus) or at an intermediate distance (with edema extending very close to the CS) independently decreased the rate at which the CS was identified by 73% (hazard ratio: 0.27, P < .001) and 55% (hazard ratio: 0.45, P = .007), respectively. Highly destructive pathology reduced this rate by 42% (hazard ratio: 0.58, P = .03), after adjusting for other important factors. Epidural recording, age, and the presence of a burst suppression pattern on the electroencephalogram had no effect. CONCLUSION: MSSEP PRT is an effective method for CS identification and only marginally lengthens the operative time. However, difficulty in CS localization can be expected in the presence of postcentral gyrus lesions, edema distorting perirolandic anatomy, and with highly destructive pathology.

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Prognostic biomarker potential of quantifying endotrophin in serum from pancreas cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16804 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16804-e16804

Author(s):

Nicholas Willumsen ◽

Inna Chen ◽

Neel Ingemann Nissen ◽

Astrid Zedlitz Johansen ◽

Julia S. Johansen ◽

...

Keyword(s):

Pancreas Cancer ◽

Cox Regression ◽

Performance Status ◽

Tumor Stage ◽

Tumor Type ◽

Cox Regression Analysis ◽

Desmoplastic Reaction ◽

Increased Risk ◽

Metastatic Sites ◽

Stage 1

e16804 Background: Pancreas cancer (PC) is the most stroma rich tumor type defined by increased collagen deposition and remodeling (desmoplasia/tumor fibrosis), which result in poor prognosis and lack of treatment response. The cleavage product of the type VI collagen alpha 3 (COL6a3) chain, also knowns as endothrophin, has been shown to signaling properties and affect several pro-tumorigenic events by augmenting desmoplasia, angiogenesis, inflammation and tumor growth. Here we evaluate the clinical utility of a biomarker (PRO-C6) quantifying endothrophin in serum from patients with PC. Methods: Serum PRO-C6 was measured by ELISA (Nordic Bioscience) in 814 PC patients (n = 15, 201, 164 and 434 for stage 1-4, respectively) and 87 patients with benign conditions from the clinical study BIOPAC (NCT03311776, Denmark). PC was histologically confirmed, and patients received standard of treatment (surgical resection or palliative chemotherapy). PRO-C6 was compared between PC and benign conditions and correlated to stage. Association between OS and PRO-C6 in PC patients was analyzed by Kaplan-Meyer curves and Cox regression analysis alone, and after adjusting for age, gender, BMI, diabetes, smoking, performance status, cachexia, CA19-9, stage and metastatic sites. Results: PRO-C6 was elevated in PC compared to benign disease (p = 0.009) and increased with tumor stage (p = 0.0006). When dividing PRO-C6 into quartiles (Q1-Q4) a stepwise decrease was detected in median OS time (Q1:380 days, Q2:264 days, Q3:236 days, Q4:176 days, p < 0.0001). Patients in Q4 had 85% increased risk of dying compared to Q1 (HR:1.85, p < 0.0001). High PRO-C6 (Q4) remained associated with poor OS after adjusting for co-variates (HR: 1.66, p = 0.0018). Conclusions: Pretreatment serum PRO-C6 (a measure of the COL6a3 chain/endothrophin) is associated with PC and has independent prognostic value. This suggests that endothrophin, and the desmoplastic reaction, plays a key role in PC and indicate that PRO-C6 may provide means for a theragnostic approach for stratifying and treating PC patients in the future. Clinical trial information: NCT03311776 .

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Increased risk of stroke in patients with diffuse idiopathic skeletal hyperostosis: a nationwide population-based cohort study

Scientific Reports ◽

10.1038/s41598-021-00798-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuan-Yang Cheng ◽

Ching-Heng Lin ◽

Po-Yi Tsai ◽

Yi-Huei Chen ◽

Shih-Yi Lin ◽

...

Keyword(s):

Cohort Study ◽

Cerebrovascular Disease ◽

Cox Regression ◽

Incidental Finding ◽

Diffuse Idiopathic Skeletal Hyperostosis ◽

Hazard Ratio ◽

Control Group ◽

Medical Database ◽

Cox Regression Analysis ◽

Increased Risk

AbstractDiffuse idiopathic skeletal hyperostosis (DISH) is frequently an incidental finding during X-ray examination. Although it has been shown to be associated with several chronic diseases, the hazard of cerebrovascular disease has seldom been explored. Our study aimed at determining the risk of stroke conferred by DISH, which is a retrospective cohort study adopting the largest medical database in Taiwan. Patients with a diagnosis of DISH at least three times from 2005 to 2010 were identified as the study group, and those in the control group were selected by matching age and gender. Patients were followed up until the end of 2015 to trace the incidence of stroke. Cox regression analysis was performed to compute the hazard ratio of stroke. Among the included 5300 patients, 1060 had a diagnosis of DISH. Significantly higher prevalence rates of stroke, hypertension, diabetes, and hyperlipidemia were noted in these patients. Overall, DISH conferred a 1.68 times higher risk of developing stroke. The significantly higher hazard ratio could be identified in both genders whether hypertension existed or not. Even in those without comorbidities, DISH still conferred a significantly higher risk of cerebrovascular disease in the future, which should never be ignored when encountered during clinical practice.

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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes

10.2337/figshare.16775743 ◽

2021 ◽

Author(s):

Anca Balintescu ◽

Marcus Lind ◽

Mikael Andersson Franko ◽

Anders Oldner ◽

Maria Cronhjort ◽

...

Keyword(s):

Type 2 Diabetes ◽

Regression Analysis ◽

Cox Regression ◽

Cubic Spline ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Increased Risk

Objective To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes and to assess the association of sepsis and all-cause mortality in such patients. Research design and methods We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between January 1, 2005 and December 31, 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. Result Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07-1.24) for HbA1c <43 mmol/mol (6.1%); 0.93 (0.87-0.99) for HbA1c 53-62 mmol/mol (7.0-7.8%); 1.05 (0.97-1.13) for HbA1c 63-72 mmol/mol (7.9-8.7%); 1.14 (1.04-1.25) for HbA1c 73-82 mmol/mol (8.8-9.7%); and 1.52 (1.37-1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73-0.82) per standard deviation, and increased thereafter (P for non-linearity <0.001). As compared to patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03-4.30). Conclusions In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a four-fold increased risk of death among those developing sepsis.

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Effect of Donor on Outcomes after Myeloablative Conditioning with Daily IV Busulfan and Fludarabine (FLUBUP) +/− TBI with Thymoglobulin: Transplants from Mismatched Unrelated Donors (MMUD) Have Worse Survival Due to Higher Transplant-Related Mortality (TRM).

Blood ◽

10.1182/blood.v108.11.5398.5398 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5398-5398

Author(s):

James A. Russell ◽

Leanne Kmet ◽

Mary Lynn Savoie ◽

Nizar J. Bahlis ◽

M. Ahsan Chaudhry ◽

...

Keyword(s):

Stem Cell ◽

Cumulative Incidence ◽

Cox Regression ◽

Hazard Ratio ◽

Donor Age ◽

Cox Regression Analysis ◽

Cell Dose ◽

Stem Cell Source ◽

Increased Risk ◽

Unrelated Donors

Abstract Historically myeloablative hematopietic stem cell transplants (SCT) from donors other than genotypically identical siblings (MRD) have had worse outcomes when the same conditioning and GVHD prevention is used. It is important to know if this is still the case when all patients receive better tolerated regimens, using i.v. rather than oral busulfan for example, and more aggressive GVHD prophyaxis. We have compared outcomes of pateints (pts) receiving myeloablative fludarabine/busulfan based conditioning (FLUBUP) between 05/99 and 05/05 according to donor. All pts received fludarabine 50mg/m2 on days -6 to -2 and IV busulfan (Busulfex, PDL Pharma) at a myeloablative dose of 3.2 mg/kg daily days -5 to -2 inclusive +/− TBI 200cGy × 2 on day -1 or 0. Prophylaxis for GVHD was cyclosporine A, methotrexate with folinic acid and Thymoglobulin (Genzyme) 4.5 mg/kg in divided doses over 3 consecutive days pretransplant finishing D0. Patients were divided into four groups depending on donor - MRD, genotypically mismatched family members (MMRD), unrelated donors matched for HLA-A, -B, C, DR & DQ (MUD) and MMUD. Of 40 MMUD 32 were mismatched for one antigen, 7 for 2 and one for 3 at least at the allelic level. Baseline and transplant characteristics MRD MMRD MUD MMUD Number 201 22 81 40 Pt age (yrs) range/mean (SD) 18–66/45 (11.0) 19–63/44 (14.9) 16–61/40 (12.3) 19–64/40 (12.2) Donor age (yrs) range/mean (SD) 15–71/44 (11.1) 10–65/35 (19.1) 19–57/32 (8.5) 21–54/33 (8.2) Male pt % 63.7 54.6 58.0 65.0 Low risk (Acute leukemia CR1/2, CML CP1) % 41.8 54.6 55.6 32.5 TBI % (not risk factor for TRM) 23.9 31.8 42.0 47.5 Blood cell SCT % 87.6 90.9 43.2 65.0 Female to male SCT % 26.9 27.3 19.8 30.0 CMV+ve donor or recipient % 77.1 54.6 69.1 55.0 CD34+ cell dose/kg - range/median (IQR) 0.8–13.6/4.7(3.4–6.0) 2.0–10.3/4.1(3.3–6.9) 0.4–23.9/3.7(2.4–7.7) 0.9–17.7/5.0(3.0–7.0) Five-year survival (OS) estimates (95% CI) were MRD 60% (52%–67%), MMRD 58% (34%–75%), MUD 57% (45%–67%), MMUD 38% (23%–53%). By Cox regression analysis MRD, MMRD and MUD SCT had similar outcomes and were combined for a more robust analysis. The hazard ratio for OS for MMUD vs all others was 2.03 (95% CI 1.31–3.16, p = 0.002). After adjusting for gender, risk group, patient age (continuous), donor age (continuous), TBI, stem cell source, female donor to male recipient, CMV status and CD34+ cell dose (continuous) the hazard ratio was 1.69 (1.04–2.74) (p = 0.03). The cumulative incidence of relapse mortality was silmiar across all 4 groups, the difference in outcome was mostly attributable to TRM. Thus the cumulative incidence of TRM at 3 years was 31.6% (17.5%–46.7%) for MMUD vs 14.5% (10.8%–18.8%) for all others. We conclude that the FLUBUP protocol +/− TBI with Thymoglobulin gives comparable OS for recipients of SCT from all donors apart from MMUD and patients should be advised of the increased risk when the latter donors are the only ones available.

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Blood Pressure Classification of 2017 Associated With Cardiovascular Disease and Mortality in Young Chinese Adults

Hypertension ◽

10.1161/hypertensionaha.119.14239 ◽

2020 ◽

Vol 76 (1) ◽

pp. 251-258 ◽

Cited By ~ 2

Author(s):

Shouling Wu ◽

Yongjian Song ◽

Shuohua Chen ◽

Mengyi Zheng ◽

Yihan Ma ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Cox Regression ◽

Chinese Adults ◽

Cox Regression Analysis ◽

Increased Risk ◽

All Cause Mortality ◽

New Guidelines ◽

Stage 1

The American College of Cardiology/American Heart Association introduced new guidelines for blood pressure (BP) classification in 2017. We explored associations between the newly defined categories and eventual cardiovascular disease (CVD) events, stroke, and all-cause mortality in young Chinese adults. In the community-based Kailuan Study, 16 006 participants aged 18 to 40 years and examined at baseline in 2006/2007 underwent 2-yearly follow-up examinations up to 2016 to 2017. Taking the highest BP reading recorded by manual sphygmomanometry at baseline in 2006 to 2007, we categorized the BP according to the new guidelines. Outcome parameters were CVD events, stroke, and all-cause mortality. During follow-up (mean: 10.9±0.63 years), we observed 458 events (CVD, 167; stroke, 119; and all-cause death, 172). After multivariable adjustment, hazard ratios for CVD events were for elevated BP 0.80 (95% CI, 0.28–2.30), stage 1 hypertension 1.82 (95% CI, 1.12–2.94), and stage 2 hypertension 3.54 (95% CI, 2.18–5.77) versus normal BP. Similar results were obtained for stroke and all-cause death. In Cox regression analysis with BP category entered as time-dependent covariate, stage 1 hypertension was not associated with increased risk ( P >0.10). In the subgroup of individuals taking antihypertensive medication during follow-up, none of the BP categories was significantly associated with the incidence of CVD events. During a mean follow-up of 10.9 years, the newly defined category of stage 1 hypertension in young untreated Chinese adults aged <40 years at baseline was associated with an increased risk for CVD, stroke, and all-cause mortality. This increased risk occurred, however, after progression to stage 2 hypertension. The data may help validating the new BP classification system for young adult Chinese.

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Prevalence of colorectal cancer biomarkers and their impact on clinical outcomes in Riyadh, Saudi Arabia

PLoS ONE ◽

10.1371/journal.pone.0249590 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0249590

Author(s):

Amjad Alharbi ◽

Haifa Bin Dokhi ◽

Ghadir Almuhaini ◽

Futoon Alomran ◽

Emad Masuadi ◽

...

Keyword(s):

Colorectal Cancer ◽

Saudi Arabia ◽

Survival Time ◽

Cox Regression ◽

Demographic Data ◽

Response To Treatment ◽

Treatment Modalities ◽

Wild Type ◽

Cox Regression Analysis ◽

Increased Risk

Objectives KRAS, NRAS, and BRAF mutations are commonly present in colorectal cancer (CRC). We estimated the frequency of KRAS, NRAS, and BRAF mutations and assessed their impact on survival and other clinical variables among Saudi patients. Design Retrospective cohort study design. Settings Oncology department of a tertiary hospital in Riyadh, Saudi Arabia. We gathered information from 2016 to 2018. Participants Cohort of 248 CRC patients to assess the demographic data, pathological tumour features, response to treatment modalities, disease progression, and metastasis. Statistical analysis used Correlation analysis using the chi-square test. Survival analysis using a Kaplan Meier method. Cox regression analysis to calculate the hazard ratios. Results Demographic data revealed that 84% of patients were diagnosed with CRC above the age of 50 years. Only 27% of patients presented with distant metastasis. KRAS mutations were the most prevalent (49.6%), followed by NRAS mutations (2%) and BRAF mutations (0.4%). Wild type tumours were found among 44.4% of patients. KRAS mutation showed no significant correlation with the site, type, pathological grade, and stage of the tumour. The mean survival time was shorter among patients with KRAS mutations than among patients with wild type KRAS tumours (54.46 vs. 58.02 months). Adjusted analysis showed that the survival time was significantly affected by patients’ age at diagnosis (P = 0.04). Male patients had an increased risk of mortality by 77% (hazard ratio: 1.77). Conclusions Saudi CRC patients had a high frequency of KRAS mutations and a low frequency of BRAF mutations. The KRAS mutation status did not affect the patients’ survival.

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