Non-cancer Group Research Articles

Verification of Saliva Matrix Metalloproteinase-1 as a Strong Diagnostic Marker of Oral Cavity Cancer.

Oral squamous cell carcinoma (OSCC) accounts for >90% of cases of oral cancer, including cancer at the lip and oral cavity and cancer at the oropharynx. Most OSCCs develop from oral potentially malignant disorders (OPMDs), which consist of heterogeneous lesions with different malignant transformation potentials that make early detection of OSCC a challenge. Using a targeted mass spectrometry-based assay to compare multiple candidate proteins, we previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary OSCC biomarkers. To explore the clinical utility of MMP-1 in OSCC detection, we developed an in-house, sensitive enzyme-linked immunosorbent assay (ELISA) for measuring MMP-1 content, and tested it on saliva samples from 1160 subjects (313 healthy controls, and 578 OPMD and 269 OSCC patients) collected at two medical centers. Salivary MMP-1 levels measured by our in-house ELISA significantly discriminated OSCC patients from non-cancerous groups. A receiver operating characteristic curve analysis showed that MMP-1 was effective in separating non-cancer groups from patients with OSCCs at the oral cavity. Additionally, salivary MMP-1 levels in oral cavity cancer patients were highly correlated with tumor progression (tumor size, lymph node metastasis, and overall stage). Collectively, our results indicate that salivary MMP-1 is an effective biomarker for OSCC that can be sensitively detected using our newly developed ELISA. The newly developed MMP-1 ELISA may be used as a new adjunctive tool to aid in detecting and monitoring OSCC.

Abstract CT021: Prediction of cancer and tissue of origin in individuals with suspicion of cancer using a cell-free DNA multi-cancer early detection test

Abstract Background: The Circulating Cell-free Genome Atlas study (NCT02889978) is a multi-center, case-control, observational study with longitudinal follow-up (n=15,254; 56% cancer, 44% non-cancer) to support development of a cell-free DNA (cfDNA) multi-cancer early detection test. Previously, we reported that a targeted methylation assay detected and localized >20 cancer types at >99% specificity in individuals with cancer.1,2 Here, we report prediction of cancer (presence/absence) and tissue of origin (TOO) in individuals enrolled with clinical suspicion of cancer but without pathologic diagnosis or treatment at time of enrollment. Methods: Plasma cfDNA from blood samples collected prior to clinical diagnosis was subjected to targeted methylation sequencing. Samples were divided into a training set and an independent validation set to train and validate a machine learning classifier to assess cancer and predict TOO. Performance was assessed in a subset of participants enrolled with suspicion of cancer; subsequently, cancer was confirmed by evaluating a pathologic specimen. Results: Participants being evaluated for suspicion of cancer were classified as confirmed cancer (>20 cancer types; n=164 in training, n=75 in validation) or confirmed non-cancer (n=49 training, n=15 validation). In the confirmed non-cancer group, all training and validation samples were correctly predicted as non-cancer (100% specificity). In the confirmed cancer group, cancer detection across all stages was 40.2% (66/164; 95% confidence interval [CI], 32.7-48.2%) in training and 46.7% (35/75; 95% CI, 35.1-58.6%) in validation. Excluding stage I renal cancers (where detection/tumor fraction is low in plasma and which comprised 20% of participants in this subset) detection across stages was 50.4% (66/131; 95% CI, 41.5-59.2%) and 59.3% (35/59; 95% CI, 45.7-71.9%), respectively. In stages II and above, detection was 70.7% (58/82; 95% CI, 59.6-80.3%) and 78.9% (30/38; 95% CI, 62.7-90.4%), respectively. For detected cancers, TOO was predicted in 93.9% (62/66) samples in training and 100% (35/35) in validation. Of those with a TOO call, accuracy was 85.5% (53/62; 95% CI, 74.2-93.1%) and 97.1% (34/35; 95% CI, 85.1-99.9%), respectively. Conclusion: A cfDNA multi-cancer detection test has shown the potential to predict cancer and TOO in individuals with suspicion of cancer ahead of histologic diagnosis with performance comparable to those with confirmed cancer at the time of blood collection. This was achieved with high specificity and TOO accuracy. The high specificity suggests that the false positive rate could be comparable in populations with average versus higher risk (suspicion) of cancer. These findings suggest that a cfDNA multi-cancer detection test could accelerate the diagnostic resolution of suspicion of cancer.

Nuclear staining of claudin-18 is a new immunohistochemical marker for diagnosing intramucosal well-differentiated gastric adenocarcinoma.

Diagnosis of gastric adenocarcinoma using small biopsy samples is occasionally difficult. Various markers have been employed for improving the diagnostic accuracy, but there remains room for improvement. A total of 129 endoscopically biopsied samples were studied, consisting of 104 intramucosal tubular adenocarcinomas, 24 non-cancerous lesions and one cancer sample originally suspected of non-cancer but revised as cancer after immunostaining. We evaluated the association between histopathology and immunohistochemical expression of MUC1, HER2, p53, CEA, E-cadherin, β-catenin and claudin-18. Regarding β-catenin and claudin-18, not only membranous expression (β-catenin(M) and claudin-18(M)) but also nuclear expression (β-catenin(N) and claudin-18(N)) were analyzed. When subtyped with mucin core protein expression, the gastric-type cancers dominantly expressed claudin-18(M), while claudin-18(N) was significantly encountered in intestinal- and mixed-types. Expression of MUC1 (P = 0.0010), HER2 (P = 0.0173), p53 (P = 0.0002), CEA (P = 0.0019) and claudin-18(N) (P < 0.0001) revealed significant correlation with gastric cancers. Negative correlation of claudin-18(M) (P = 0.0125) was also noted. MUC1 and p53 were negative in non-cancer lesions. The non-cancer group exceptionally expressed HER2 and β-catenin(N). Membranous expression of E-cadherin was consistent in both groups. Logistic regression analysis showed that MUC1 (P = 0.0086), p53 (P = 0.0031), claudin-18(M) (P = 0.0158) and claudin-18(N) (P = 0.0190) were independently associated with gastric cancers. Nuclear expression of claudin-18 should be the novel diagnostic marker for gastric cancer.

Risk of osteoporosis and fracture in long-term breast cancer survivors.

High incidence of osteoporosis has been reported in breast cancer patients due to early menopause triggered by adjuvant treatment and temporary ovarian function suppression. In this study, we sought to determine whether long-term breast cancer survivors had an elevated risk of low bone density compared to the general population. Long-term breast cancer survivors who had been treated for more than 5 years were selected for this study. Data were obtained from medical records and using a questionnaire from the Korea National Health and Nutrition Examination Survey (KNHANES). An age-matched non-cancer control group was selected from the KNHANES records. Incidence of fracture and bone mineral density (BMD) were compared between the two groups. In total, 74 long-term breast cancer survivors and 296 non-cancer controls were evaluated. The incidence of fracture did not differ between the two groups (P=0.130). No differences were detected in lumbar BMD (P=0.051) following adjustment for body mass index, while hip BMD was significantly lower in breast cancer survivors (P=0.028). Chemotherapy and endocrine treatment were not related to low BMD in breast cancer survivors. In more than half of the survivors, the 10-year risk of osteoporotic fracture was less than 1%. Long-term breast cancer survivors had low bone density but a comparable risk of fracture compared to non-cancer age-matched controls. Further studies on the factors related to low bone density in long-term breast cancer survivors are required.

Fertility under uncertainty: exploring differences in fertility-related concerns and psychosocial aspects between breast cancer survivors and non-cancer infertile women.

The threat to fertility due to anticancer treatments can be distressing to women who wish to complete their family. The current study assessed the fertility-related concerns, psychological distress and health-related quality of life (HRQoL) of breast cancer survivors in comparison to non-cancer women with infertility history and to healthy controls from the general population. We surveyed young adult women aged 18 to 40 who wished to have a (or another) biological child. Participants completed self-report measures assessing fertility concerns, anxiety, depression and physical, emotional, role and social functioning. Group differences were assessed using multivariate comparisons as well as univariate tests and discriminant analysis for individual measures. A total of 136 women were recruited, of whom 43 were breast cancer survivors, 56 non-cancer infertile women and 37 healthy controls. Considering the female cancer survivors as the focus of the analysis, data suggested that these women presented identical concerns to the non-cancer infertile group and higher than the healthy women with regard to fertility potential (p < 0.01). However, women diagnosed with cancer reported worse HRQoL than their counterparts, showing lower scores in physical functioning (p < 0.05) than infertile women and lower role (p < 0.05) and social HRQoL (p < 0.01) than the controls. Anxiety and depressive symptoms did not differ between the three groups. The results suggest that living with uncertainty about reproductive potential after cancer can be a disruptive experience. Breast cancer survivors and infertile women are at risk of future emotional maladjustments, given the reported level of fertility concern.

Hematological Abnormalities and Malnutrition Mediate Pathway between Cancer and Outcomes in Ischemic Stroke Patients

BackgroundThe present study aimed to examine whether variables including D-dimer, high-sensitivity C-reactive protein (hsCRP), hemoglobin, platelet count, and nutritional status mediate the pathway between cancer and ischemic stroke outcomes. MethodsWe reviewed data from consecutive patients with ischemic stroke admitted to Osaka University Hospital between January 1, 2006, and December 31, 2016. Patients with ischemic stroke were grouped according to the presence of cancer. Nutritional status was assessed using Controlling Nutritional Status (CONUT) scores. Mediation analyses were utilized to address the study aims. ResultsAmong 1,570 patients with ischemic stroke, 185 (12%) had active cancer. Relative to patients with ischemic stroke in the non-cancer group, those in the cancer group exhibited higher National Institutes of Health Stroke Scale scores on admission, higher D-dimer and hsCRP levels, lower hemoglobin levels and platelet counts, higher CONUT scores, and poorer modified Rankin Scale scores at discharge. Mediation analysis revealed that D-dimer, hsCRP, hemoglobin, platelet count, and CONUT scores acted as mediators of poor prognosis in the cancer group. The association between the exposure and outcome variables was no longer significant in the models containing D-dimer and CONUT scores as mediator variables, suggesting that they were strong mediators. Regarding the association between the mediator and outcome variables, hemoglobin, platelet count, and CONUT exhibited non-linearity (p for non-linearity < 0.001). ConclusionsD-dimer, hsCRP, hemoglobin, platelet count, and CONUT score act as mediators of poor prognosis in patients with ischemic stroke with comorbid cancer. Such abnormalities can help to predict ischemic stroke outcomes.

Obstetrical and perinatal complications in survivors of childhood, adolescent, and young adult cancer: A population-based study.

10529 Background: Women who survive cancer diagnosed in childhood, adolescence or young adulthood may develop long-term health issues. Data are lacking on adverse reproductive outcomes such as infertility and obstetrical and perinatal complications. Methods: Using linked Ontario provincial cancer and obstetrical registries, we assembled a cohort of female cancer survivors diagnosed before age 21 years from 1985-2012. We matched survivors by age and geographic region to females without a prior cancer diagnosis. Outcomes included i) any recognized and past 20 weeks’ gestation pregnancy; ii) perinatal complications; and iii) obstetrical complications (including a broad composite of severe maternal morbidity [SMM]). Multivariable Cox proportional hazard and modified Poisson models compared survivors to a non-cancer group and assessed demographic, diagnostic and treatment risk factors in survivors. Results: 3,486 survivors were matched to 17,428 women without prior cancer. Median age at cancer diagnosis was 12 years (IQR 5-16) and median follow-up was 26 years (IQR 21-32). 599 (17.2%) survivors had at least one recognized pregnancy compared to 3,885 (22.3%) women without prior cancer (Hazard Ratio [HR] 0.79, 95% Confidence Interval [CI] 0.7-0.9, p &lt; .0001). Among those who had a recognized pregnancy, 581 (97.0%) survivors carried a pregnancy &gt; 20 weeks’ gestation vs. 3791 (97.6%) in the non-cancer group (Relative Risk [RR] 1.0, CI 0.98-1.04). Factors significantly associated with a decreased likelihood of achieving at least one recognized pregnancy among survivors included brain tumour, cranial radiation, exposure to an alkylating agent or hematopoietic stem cell transplantation (HSCT). Among women who had a livebirth or stillbirth, survivors had a RR of 2.3 (CI 1.5-3.6) for SMM and 3.2 (CI 1.6-6.6) for cardiac morbidity. Factors associated with SMM among survivors included brain tumour and pre-existing kidney disease. Among livebirth pregnancies, cancer survivors were at higher risk of preterm birth (RR 1.6, CI 1.2-2.0), especially those who received an alkylating agent or HSCT. Conclusions: Survivors of childhood, adolescence or young adulthood cancer are less likely to achieve a recognized pregnancy compared to women without prior cancer. Those who carry a pregnancy &gt;20 weeks’ gestation are at higher risk for SMM and preterm birth. Fertility planning and counseling can be informed by cancer diagnosis and treatment, and high-risk obstetrical care is recommended for survivors at elevated risk of an adverse pregnancy outcome.

Analysis of the Time Interval between the Physician Order for Life-Sustaining Treatment Completion and Death.

BackgroundThis study aimed to explore the time interval distribution pattern between the Physicians Order for Life-Sustaining Treatment (POLST) form completion and death at a tertiary hospital in South Korea. It also examined the association between various independent parameters and POLST form completion timing.MethodsA total of 150 critically ill patients admitted to Korea University Guro Hospital between June 1, 2018 and December 31, 2018 who completed the POLST form were retrospectively analyzed and included in this study. Data were analyzed with descriptive statistics, and group comparisons were performed using the chi-square test for categorical variables. Fisher’s exact test was also used to compare cancer versus non-cancer groups.ResultsMore than half the decedents (54.7%) completed their POLST within 15 days of death and 73.4% within 30 days. The non-cancer group had the highest percentage of patients (77.8%) who died within 15 days of POLST form completion while the colorectal (39.1%) and other cancer (37.5%) groups had the lowest (P=0.336).ConclusionOur findings demonstrated a current need for more explicit guidance to assist physicians with initiating more timely, proactive end-of-life discussions.

Characterization of urinary microbiome in patients with bladder cancer: Results from a single-institution, feasibility study

ObjectivesThe human microbiome has been linked to the development of several malignancies, but there is scarcity of data on the microbiome of bladder cancer patients. In this study, we analyzed microbial composition and diversity among patients with and without bladder cancer. Material and MethodsSamples were collected from 38 urothelial carcinoma (UC) patients and 10 noncancer controls from August 2018 to May 2019. DNA was extracted and processed for 16 S ribosomal RNA sequencing. Alpha diversity community characteristics including evenness and richness as well as beta diversity metrics were obtained. Linear discriminant analysis effect size was used to identify microbial components whose sequences were more abundant. Pairwise statistics provided quantitative assessment of significant distributions among groups. ResultsThirty seven total samples contained high quality sequence data for subsequent analyses and divided into 3 cohorts: control (n = 10), muscle-invasive (n = 15) and superficial UC (n = 12). Control samples had significantly higher species evenness when compared to invasive (P = 0.031) and superficial tumors (P = 0.002). In addition, higher species richness was observed in noncancer versus cancer samples (Faith phylogenetic diversity, P < 0.05). Significantly enriched taxa were found in both control (Bacteroides, Lachnoclostridium, Burkholderiaceae) and cancer samples (Bacteroides and Faecalbacterium). ConclusionSignificantly decreased microbial community diversity was seen in the urine of patients with bladder cancer when compared to a noncancer group. Distinct taxa were noted suggesting unique microbial communities in the urine of bladder cancer patients.

Cancer Cachexia May Hinder Pain Control When Using Fentanyl Patch.

The objective of this study was to evaluate the influence of cancer cachexia on pain control in cancer patients receiving a transdermal fentanyl patch (FP) and to investigate whether dry skin was a factor related to cancer cachexia and uncontrolled pain. We retrospectively reviewed the medical records of 77 patients receiving FP treatment for the first time, who were classified into cancer cachexia and non-cancer-cachexia groups, according to European Palliative Care Research Collaborative criteria. On day 7 after FP administration, the mean FP dose and morphine equivalent dose (MED) in the cancer cachexia group were significantly higher than in the non-cancer-cachexia group. Additionally, in the cancer cachexia group, there was a significantly larger degree of variation in pain intensity over 7 d than in the non-cachexia group. In patients who were switched from FP to morphine injection, the mean pain intensity and MED on day 3 after morphine injection were significantly lower than those immediately before morphine injection. Subsequently, to investigate whether dry skin was involved in poor pain control in the cancer cachexia group, transepidermal water loss (TEWL) was compared between 15 additional patients classified into cancer cachexia and non-cancer cachexia groups; the mean TEWL in the cancer cachexia group was found to be significantly lower. Our data suggest that cancer cachexia may be a risk factor for poor pain control in patients receiving FP treatment, and that uncontrolled pain in FP treatment may be caused by the inhibition of fentanyl transdermal absorption due to dry skin.

Diagnostic Performance of the Support Vector Machine Model for Breast Cancer on Ring-Shaped Dedicated Breast Positron Emission Tomography Images.

The aim of this study was to evaluate the diagnostic ability of support vector machine (SVM) for early breast cancer (BC) using dedicated breast positron emission tomography (dbPET). We evaluated 116 abnormal fluorodeoxyglucose (FDG) uptakes less than 2 cm on dbPET images in 105 women. Fluorodeoxyglucose uptake patterns and quantitative PET parameters were compared between BC and noncancer groups. Diagnostic accuracy of the SVM model including quantitative parameters was compared with that of visual assessment based on FDG-uptake pattern. Age, maximum standardized uptake value, peak standardized uptake value, total lesion glycolysis, metabolic tumor volume, and lesion-to-contralateral background ratio were significantly different between BC and noncancer groups. Area under the curve, sensitivity, specificity, and accuracy for FDG-uptake pattern of visual assessment were 0.77, 0.57, 0.77, and 0.71, respectively; those of an SVM model including age, maximum standardized uptake value, total lesion glycolysis, and lesion-to-contralateral background ratio were 0.89, 0.94, 0.77, and 0.85, respectively. Support vector machine showed high diagnostic performance for BC using dbPET.

Pain Intervention for Cancer and Non-cancer Pain: A Retrospective Analysis of Tertiary Care Hospital Experience.

BackgroundWith the recent advancement in medicine there has been a great emphasis on the management of chronic pain which remains as one of the major contributing factors for functional limitation in patients as well as a financial burden on healthcare. Newer treatment modalities are aimed at terminating the vicious pain cycles and in this regard peripheral nerve blocks have proven to be very effective.ObjectivesThe aim of this study is to evaluate the effectiveness of interventions for both cancer and non-cancer patients by objective assessment of the patients before and after the procedure.Materials and methodsThe study included 252 patients who underwent nerve block procedures in Shaukat Khanum Memorial Cancer Hospital from December 2016 to December 2018. The patients were evaluated using numerical rating scale (NRS) for pain, reduction in analgesic doses and patient satisfaction after one and four weeks post procedure. The data was analyzed using mean values and calculating percentages.ResultsIn cancer group, 168 patients were included; mean age 50.49 ± 15.39 with 46.43% females and 53.57% males, the average pain score was 2.62 ± 1.87 post procedure compared with 6.30 ± 1.87 post procedure. 48.21% of the patients reported a reduction in analgesia while 51.79% of the patients kept on using the same analgesics doses. 74.40% of the patients were satisfied and 25.60% patients remained unsatisfied after one week whereas 66.07% were satisfied, 23.81% were not satisfied and 10.12% loss to follow up after four weeks. In non-cancer group 84 patients were included; mean age 56.49 ± 15.79 with 41.67% females and 58.33% males, the average pain score before intervention was 5.99 ± 1.21 and after intervention it was 2.43 ± 1.62. In 73.81% non-cancer patients the analgesics doses were reduced and 70.24% patients were satisfied while 29.76% were unsatisfied after one week. After four weeks 55.95% were satisfied, 22.62% were not satisfied and 21.43% loss to follow up.ConclusionThe study showed decrease in pain scores in both group of patients and the importance of nerve blocks as an effective method for chronic pain management. The reduction in the use of other analgesics was also commendable in both the groups.

Screening and Intervention for Skin Cancer in the Galapagos.

This study aimed to assess the general dermatological needs and correlation of tentative skin cancer screening diagnoses with histopathological confirmation in the highly sun-exposed locals of the Galapagos Islands. An institutional review board-approved prospective study was performed at Blanca's House, a nonprofit surgical volunteer organization, free clinics in the Galapagos. After consent, a 40-item modified SPOTme-inspired questionnaire was completed. Partial or total body skin examinations were conducted by board-certified dermatologists. Board-certified plastic and general surgeons performed excisional biopsies on suspicious lesions. Individuals younger than 18 years, and non-Spanish or non-English speakers were excluded. A total of 273 patients were included in the study, of which 202 reported skin concerns. Benign nevi (n = 76), seborrheic keratosis (n = 42), melasma (n = 19), actinic keratosis (n = 16), acne (n = 15), eczema (n = 13), fungal infections (n = 12), seborrheic dermatitis (n = 5), and psoriasis (n = 5) were most commonly identified.Twelve patients (4.4%) had presumptive skin cancer after screening. Six of 8 biopsies confirmed cancer (group 1), 2 declined a biopsy and 2 were unresectable. Seven basal cell carcinomas and one squamous cell carcinoma were excised with clear margins. A right lower eyelid melanoma was diagnosed and subsequently treated in the United States where invasive melanoma with a Breslow thickness of 0.3 mm was found.Compared with the noncancer group (group 2: n = 265), group 1 had significantly higher likelihood of reporting having seen a dermatologist (P = 0.02), taking any medications (P = 0.0001), having blonde or red hair (P = 0.01), having blue or green eyes (P < 0.0001), and having used indoor tanning equipment (P < 0.0001). Group 1 was also more likely to report 4 or more blistering sunburns (P = 0.08), which approached significance. When evaluated by a dermatologist, group 1 was significantly more likely to be classified as "high risk" for developing cancerous lesions (P < 0.0001) compared with group 2. Skin concerns in the Galapagos included benign and malignant conditions. There is a need for dermatological care in this medically underserved population. This modified SPOTme-inspired skin cancer questionnaire, confirmed by histology, is a useful tool in identifying high-risk patients and detecting skin cancer in international communities that would have otherwise experienced delays in diagnosis or treatment.

Association of Nijmegen Breakage Syndrome 1 Genotypes With Bladder Cancer Risk

We aimed to examine the association of the genotypes of Nijmegen breakage syndrome 1 (NBS1), a critical gene in DNA double strand break repair machinery, with bladder cancer risk in Taiwan. NBS1 rs1805794 genotypes among 375 bladder cancer patients and 375 non-cancer healthy controls were determined via the polymerase chain reaction-restriction fragment length polymorphism methodology and their association with bladder cancer risk were evaluated. The results showed that the percentages of GG, CG and CC of NBS1 rs1805794 genotypes were 45.4%, 43.7% and 10.9% in the bladder cancer patient group and 47.2%, 43.2% and 9.6% in the non-cancer control group, respectively (p for trend=0.7873). The analysis of allelic frequency distributions showed that the variant C allele of NBS1 rs1805794 does not contribute to an increased bladder cancer susceptibility (p=0.5066). The genotypes of NBS1 rs1805794 are not closely associated with personal susceptibility to bladder cancer.

Clinical features and diagnosis of new malignancy in patients with acute pulmonary embolism and without a history of cancer.

Pulmonary embolism (PE) is frequently associated with cancer. This study aimed to assess patients with acute PE and identify diagnostic predictors of new cancer after 1 year of follow-up. One hundred and twenty-one patients with PE were enrolled consecutively from the emergency department of a single medical center in Taiwan. Data from computed tomography angiography, echocardiogram, electrocardiogram and for baseline comorbidities, clinical presentation, and laboratory parameters were recorded. The surviving discharged patients without a cancer diagnosis were followed-up for 1 year, and new malignancies were recorded. Of 121 patients with acute PE, 44 (36%) had an underlying cancer history (cancer group), and 77 (64%) did not (noncancer group). Baseline demographic characteristics, comorbidities, clinical symptoms, biochemical parameters, echocardiogram data, and electrocardiogram data of the two groups were similar except for a higher hospital mortality rate (56.8% vs 9.1%; p < 0.001), lower body mass index (22.6 ± 4.1 vs 25.5 ± 4.9; p =0.02), higher systolic blood pressure (139.7 ± 33.7 vs 125.4 ± 24.1; p = 0.02), lower low-density lipoprotein level (67.4 ± 38.3 vs 90.4 ± 33.8; p = 0.04), lower creatinine kinase (CK; 43.0 ± 43.0 vs 83.5 ± 83.1; p = 0.01), higher myocardial band (MB) form of CK ratio (0.2 ± 0.2 vs 0.1 ± 0.1; p < 0.01), higher partial pressure of arterial oxygen (122.81 ± 81.2 vs 90.2 ± 59.4; p = 0.03), and less presentation of chest pain (15.9% vs 40.3%; p = 0.01) in the cancer group. Kaplan-Meier curve analysis revealed that the 30-day survival rate was higher in the noncancer group than in the cancer group (log-rank p = 0.04). After 1 year of follow-up, 6 of 59 (10.17%) initial non-cancer-related PE survivors were diagnosed with malignancies. After multivariate analysis, only the initial CK-MB level was associated with a diagnosis of new cancer (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.029-1.811; p = 0.03). This study suggests that the CK-MB level is associated with future malignancy in patients with PE. Patients with cancer-related PE had a worse 30-day survival rate.

Worry About Daily Financial Needs and Food Insecurity Among Cancer Survivors in the United States.

A cancer diagnosis can impose substantial medical financial burden on individuals and may limit their ability to work. However, less is known about worry for nonmedical financial needs and food insecurity among cancer survivors. The National Health Interview Survey (2013-2017) was used to identify cancer survivors (age 18-39 years, n=771; age 40-64 years, n=4,269; age ≥65 years, n=7,101) and individuals without a cancer history (age 18-39 years, n=53,262; age 40-64 years, n=60,141; age ≥65 years, n=30,261). For both cancer survivors and the noncancer group, adjusted proportions were generated for (1) financial worry ("very/moderately/not worried") about retirement, standard of living, monthly bills, and housing costs; and (2) food insecurity ("often/sometimes/not true") regarding whether food would run out, the fact that food bought did not last, and the inability to afford balanced meals. Further adjusted analyses examined intensity measures ("severe/moderate/minor or none") of financial worry and food insecurity among cancer survivors only. Compared with individuals without a cancer history, cancer survivors aged 18 to 39 years reported consistently higher "very worried" levels regarding retirement (25.5% vs 16.9%; P<.001), standard of living (20.4% vs 12.9%; P<.001), monthly bills (14.9% vs 10.3%; P=.002), and housing costs (13.6% vs 8.9%; P=.001); and higher "often true" levels regarding worry about food running out (7.9% vs 4.6%; P=.004), food not lasting (7.6% vs 3.3%; P=.003), and being unable to afford balanced meals (6.3% vs 3.4%; P=.007). Findings were not as consistent for cancer survivors aged 40 to 64 years. In contrast, results were generally similar for adults aged ≥65 years with/without a cancer history. Among cancer survivors, 57.6% (age 18-39 years; P<.001), 51.9% (age 40-64 years; P<.001), and 23.8% (age ≥65 years; referent) reported severe/moderate financial worry intensity, and 27.0% (age 18-39 years; P<.001), 14.8% (age 40-64 years; P<.001), and 6.3% (age ≥65 years; referent) experienced severe/moderate food insecurity intensity. Lower income and higher comorbidities were generally associated with greater intensities of financial worry and food insecurity in all 3 age groups. Younger cancer survivors experience greater financial worry and food insecurity. In addition to coping with medical costs, cancer survivors with low income and multiple comorbidities struggle to pay for daily living needs, such as food, housing, and monthly bills.

Sal-Like Protein 4 Transcription Factor: A Significant Diagnostic Biomarker Involved in Childhood ALL Resistance and Relapse.

PurposeSal‐like protein 4 transcription factor (SALL4) is a stem cell transcription factor that plays an essential role in the maintenance and self-renewal of embryonic and hematopoietic stem cells, functioning as an oncogene in several cancers. However, the role of SALL4 in the biological behavior of childhood acute lymphoblastic leukemia and its relationship with multidrug resistance and relapse has remained largely unknown.Patients and MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was used to characterize the expression pattern of SALL4 in the bone marrow samples of 43 patients with Philadelphia negative ALL and 18 children in the non-cancer control group. The presence of minimal residual disease was measured a year after the initial therapy using SSCP (single-strand conformation polymorphism). In addition, the correlation between the expression of SALL4 and ABCA3 in relapsed patients was analyzed statistically.ResultsResults showed an overexpression of SALL4 in de novo patients compared with the control group (P=0.0001, AUC= 0.93), indicating the importance of this gene in the induction of leukemia. A significant increase in the ABCA3 expression levels was revealed in the relapsed patients, in comparison with the drug-sensitive group (P = 0.0005). The leukemogenetic effect of SALL4 can be related to the effect of this gene on the maintenance of pluripotency in cancer stem cells. Results also suggest that the expression of SALL4 can be considered as a diagnostic marker for pediatric ALL. Moreover, SALL4 expression levels in the minimal residual disease positive (mrd+) ALL group was significantly higher than those in the mrd− group (p=0.0001, AUC= 0.92).ConclusionThese data demonstrate the prognostic impact of SALL4 in childhood ALL. Our findings also indicated a direct correlation between the mRNA expression levels of SALL4 and ABCA3 transporter in the relapsed group of ALL patients (r=0.7). These results describe a possible mechanism by which SALL4 may lead to the development of multidrug resistance.

Anti-Mullerian hormone levels in female cancer patients of reproductive age in Indonesia: A cross-sectional study.

Background: Efforts in reproductive preservation for cancer patients have become one of the important aspects of cancer management. In fact, decline in reproductive function is known to occur after exposure to anti-cancer treatments. Measuring anti-Müllerian hormone (AMH) levels is known to be the best parameter in predicting ovarian reserves, which indicates reproductive function. In total, 68% of cancer survivors of reproductive age who underwent anti-cancer treatments suffer from infertility. Meanwhile, ovarian reserves also decrease with increasing age. There is ongoing debate on whether the ovarian reserves of cancer patients could be reduced long before exposure to anti-cancer therapy. Therefore, it is important to know whether ovarian reserves in cancer patients decrease before or after anti-cancer therapy. This can help predict the reproductive function in such cases and the effectiveness of ovarian preservation efforts. Methods: A cross-sectional study was conducted, comparing the AMH levels of 44 female cancer patients of reproductive age before cancer therapy, to 44 non-cancer patients of reproductive age (age matched) .The AMH was determined from blood.The biological ages from both groups were adjusted using the Indonesian Kalkulator of Oocytes. Results: The median age in both groups was 28 years old. The AMH levels in the blood of the cancer group were found to be significantly lower in contrast to those in the non-cancer group (1.11 [0.08-4.65] ng/ml vs. 3.99 [1.19- 8.7]; p- value <0.001). Therefore, the biological age in the cancer group was 10 years older than that of the non-cancer group, indicating that ovarian aging occurs earlier in cancer patients. Conclusions: AMH levels of cancer patients of reproductive age were already reduced before cancer therapy, given an older biological age, in contrast to that of the non-cancer patients. Proper counseling and implementation of fertility-preserving methods is highly recommended in this group of patients.

Comparison of bowel dysfunction between colorectal cancer survivors and a non-operative non-cancer control group.

Low anterior resection syndrome (LARS) detrimentally affects quality of life in colorectal cancer survivors. This study assessed the prevalence for LARS in colorectal cancer survivors and the same symptoms in a matched control group. Validated instruments, the LARS score and Short Form Survey 12, used to collect functional and quality of life outcomes from patients who had undergone distal colorectal resection at Auckland Hospital (2008-2015) or Dunedin Hospital (2008-2017). A matched non-operative control group was drawn from patients undergoing surveillance colonoscopy. The response rate was 79%. Cross-sectional prevalence of major LARS in rectal cancer patients was 52% at a median follow-up of 52months. Major LARS prevalence in the sigmoid cancer resection and non-cancer control groups was similar (25% vs 26%, P=0.6). On univariate analysis anastomotic height [risk ratio (RR) for low anterior resection4.6, P<0.001; ultralow anterior resection RR=15.5, P<0.001], radiotherapy (RR=2.6; P=0.009), stoma (RR=3.6; P=0.001) and J pouch reconstruction (vs straight anastomosis, RR=4.6; P=0.008) were associated with major LARS for rectal cancer patients. These factors were not significant when the analysis was stratified for anastomotic height. Despite correlation between LARS and Short Form Survey 12 outcomes (physical ρ=-0.2; mental ρ=-0.2) there was no difference in quality of life outcomes between the groups. Bowel dysfunction after low anterior resection affects the majority of rectal cancer patients. The high background rate of bowel dysfunction must be considered when assessing the prevalence of LARS.

Assessing potential mechanisms of arsenic-induced skin lesions and cancers: Human and in vitro evidence

Environmental exposure to arsenic is a major public health challenge worldwide. In detailing the hallmark signs of chronic arsenic exposure, previous studies have shown that epigenetic and immune dysfunction are associated with arsenic-induced skin lesions; however, knowledge regarding interactions between the mechanisms listed above is limited. In this study, a total of 106 skin samples were collected over the past 20 years. Based on the presence or absence of high arsenic exposure, the participants were divided into arsenic exposure (72) and reference (34) groups. Additionally, the arsenic exposure group was further divided into the non-cancer group (31, including skin hyperpigmentation and hyperkeratosis) and the skin cancer group (41, including Bowen’s disease, basal cell carcinoma and squamous cell carcinoma) according to a skin histopathological examination. First, the associations among miR-155, NF-AT1 with immunological dysfunction and arsenic-induced skin lesions and carcinogenesis were confirmed using these skin samples. In the arsenic-exposed group, miR-155–5p, keratin 1(Krt1), keratin 10 (Krt10), and keratin 6c (Krt6c) were significantly increased in the skin (p < 0.05), while NF-AT1, interleukin-2 (IL-2), and interferon-γ (IFN-γ) were significantly decreased (p < 0.05). Clear correlations were observed among these factors (p < 0.05). In immortalized human keratinocytes, silencing and overexpression of NF-AT1 could alter the expression and secretion of immunological dysfunction indicators (IL-2 and IFN-γ) that are induced by arsenic exposure (p < 0.05); however, miR-155–5p levels did not change significantly (p > 0.05). The miR-155–5p mimic and inhibitor could regulate the NF-AT1-mediated immunological dysfunction caused by arsenic (p < 0.05). Our study provides some limited evidence that miR-155–5p regulates the NF-AT1-mediated immunological dysfunction that is involved in the pathogenesis and carcinogenesis of arsenic. The second major finding was that Krt1 and Krt10 are markers of hyperkeratosis caused by arsenic, and Krt6c is a potential biomarker that can reflect arsenic carcinogenesis.