Dickkopf 1 is expressed in normal fibroblasts during early stages of colorectal tumorigenesis

Clinical and Translational Gastroenterology

METHODS:In a propensity score–matched cohort derived from a large nationwide database, 4-year effectiveness was compared between patients initiated on Tac and those initiated on IFX. The primary outcome was the colectomy rate during the index hospitalization. We also analyzed the cumulative medication discontinuation, UC-related rehospitalization, and colectomy rates after discharge.RESULTS:Among 29,239 hospitalized patients, 4,565 were extracted for eligibility, of whom 2,170 were treated with Tac and the remaining 2,395 with IFX. After propensity score matching, 1,787 patients were selected for each group. During the index hospitalization, excluding patients who switched to another molecular-targeted agent, the colectomy rate was higher in the Tac group than in the IFX group (7.8% vs 4.2%, P< 0.01). Among patients discharged without colectomy, the cumulative medication discontinuation (28.4 …

Endoscopy International Open

Background and study aims Endoscopic hemostasis is a life-saving procedure for gastrointestinal bleeding; however, training for it is often performed on real patients and during urgent situations that put patients at risk. Reports of simulation-based training models for endoscopic hemostasis are scarce. Herein, we developed a novel simulator called “Medical Rising STAR-Ulcer type” to practice endoscopic hemostasis with hemoclips and coagulation graspers. This study aimed to evaluate the reproducibility of the clinical difficulty of this model and the effectiveness of simulation-based training for clipping hemostasis. Patients and methods This was a prospective educational study. Fifty gastroenterology residents from Japan and Canada were recruited to participate in a simulation-based training program. The primary outcome was the success rate for clipping hemostasis. We …

Surgical endoscopy

Background and Aims The therapeutic outcome of endoscopic submucosal dissection (ESD) for large protruding tumors has not yet been evaluated. We aimed to compare the outcomes of ESD in protruding tumors with those of laterally spreading tumors (LSTs). Methods Endoscopic submucosal dissection was attempted in 218 patients with 220 colorectal tumors ≥30 mm in diameter (67, protruding tumors; 153, LSTs) from July 2007 to June 2014. We retrospectively reviewed patient medical records, therapeutic outcomes, and procedure-related adverse events. This study defined lesions with a height of 10 mm or more as protruding tumors and those with a height under 10 mm as LSTs. Results The mean lesion diameter, height, and volume were 43.8, 9.5 mm, and 13.6 cm3, respectively. The mean procedure time was …

Journal of Gastroenterology and Hepatology

Background and Aim Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real‐world drug‐prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs). Methods Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed. Results Among pregnant IBD patients, 74.4% received at least one medication from 90 days before pregnancy to 90 days after …

Journal of Gastroenterology

BackgroundThis study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies.MethodsA retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status.ResultsGenotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of …

Journal of Controlled Release

Pancreatic cancer is characterized by a densely fibrotic stroma. The fibrotic stroma hinders the intratumoral penetration of nanomedicine and diminishes therapeutic efficacy. Fibrosis is characterized by an abnormal organization of extracellular matrix (ECM) components, namely the abnormal deposition and/or orientation of collagen and fibronectin. Abnormal ECM organization is chiefly driven by pathological signaling in pancreatic stellate cells (PSCs), the main cell type involved in fibrogenesis. However, whether targeting signaling pathways involved in abnormal ECM organization improves the intratumoral penetration of nanomedicines is unknown. Here, we show that targeting transforming growth factor-β (TGFβ)/Rho-associated kinase (ROCK) 1/2 signaling in PSCs normalizes ECM organization and concomitantly improves macromolecular permeability of the fibrotic stroma. Using a 3-dimensional cell culture …

Internal Medicine

A 46-year-old Japanese man was referred to our hospital because of a marked increase in his eosinophil count (22,870/μL) and elevated liver enzyme levels. Computed tomography (CT) showed thrombi measuring approximately 8 cm in both femoral veins. A liver biopsy revealed eosinophilic infiltration, hepatocyte necrosis, fibrosis, and multiple thrombi. We suspected acute liver injury and deep vein thrombosis associated with hypereosinophilic syndrome and initiated steroids and heparin treatment. Four days after starting treatment, the patient experienced sudden chest pain and cardiopulmonary arrest. CT revealed bilateral pulmonary artery thrombosis, and despite administration of a tissue plasminogen activator, the patient died.

Pancreatology

Background/objectivesThe association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan.MethodsWe conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis.ResultsThe SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05–1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99–5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent …

Cancer Science

Pancreatic cancer (PC) is a challenging malignancy to treat. Mac‐2‐binding protein glycan isomer (M2BPGi) is a novel serum marker of liver fibrosis and hepatocellular carcinoma and is secreted by hepatic stellate and stroma cells. Serum M2BPGi levels are upregulated in PC patients. We measured the expression of M2BPGi in the serum of 27 PC patients and determined whether M2BPGi affects the malignant potential of PC cells in vitro. We also examined the effect of M2BP on PC tumor growth and gemcitabine sensitivity in vivo. Serum M2BPGi levels in PC patients were higher compared with those of healthy subjects. M2BPGi extraction in cancer‐associated fibroblasts (CAFs) was higher compared with that of PC cells. M2BPGi treatment promoted the proliferation and invasion of PC cells. The suppression of galectin‐3, which binds to M2BPGi, did not affect the proliferation‐promoting effect of M2BPGi in PC …

Intestinal Research

MethodsWe measured antibody titers specific for measles, rubella, mumps, and varicella viruses in IBD patients under immunosuppressive therapy. Those with negative titers and without vaccination history were judged unimmunized. Patients were administered vaccines while continuing VDZ or switched to VDZ if receiving other advanced therapies and then administered vaccines. Co-primary outcomes were the rate of maintaining disease severity after vaccination and the rate without vaccine-induced infection.ResultsAmong 107 unimmunized patients, 37 agreed to receive live-attenuated vaccines while continuing VDZ (17 patients) or after switching to VDZ (20 patients). In the 20 patients who electively switched to VDZ, disease severity was maintained except for 1 patient who developed intestinal infection. After 54 weeks, 18 patients (90%) continued to receive VDZ, excluding 2 patients who reverted to their originally administered biologics. In all 37 patients administered live-attenuated vaccines under VDZ treatment, disease severity was maintained after vaccination. Antibody titers became positive or equivocal in 34 patients (91.9%). There were no cases of vaccine-induced infection during a median observation period of 121 weeks.ConclusionsWhile live-attenuated vaccines are contraindicated under immunosuppressive therapy, they may be safely administered while receiving VDZ immunotherapy. Switching from other advanced therapies to VDZ and subsequently receiving live-attenuated vaccines may be a safe alternative in unimmunized patients.

Digestion

MethodsWe collected admission data for patients with acute uncomplicated diverticulitis using a nationwide database. We divided eligible admissions into two groups according to antibiotic initiation within 2 days after admission (antibiotic group vs. nonantibiotic group). We conducted propensity score matching and compared the rates of surgery (intestinal resection and stoma creation), in-hospital death, and medical costs between the groups. We also performed multivariate analysis to identify the clinical factors that affect surgery.ResultsWe enrolled 131,936 admissions; among these, we obtained 6,061 pairs after propensity score matching. Rates of both intestinal resection and stoma creation in the antibiotic group were lower than those in the nonantibiotic group (0.61 vs. 3.09%, p< 0.0001, and 0.08 vs. 0.26%, p= 0.027, respectively). Median costs in the antibiotic group were higher than those in the nonantibiotic …

Cell Reports

Clinical evidence has revealed that high-level activation of NRF2 caused by somatic mutations in NRF2 (NFE2L2) is frequently detected in esophageal squamous cell carcinoma (ESCC), whereas that caused by somatic mutations in KEAP1, a negative regulator of NRF2, is not. Here, we aspire to generate a mouse model of NRF2-activated ESCC using the cancer-derived NRF2L30F mutation and cancer driver mutant TRP53R172H. Concomitant expression of NRF2L30F and TRP53R172H results in formation of NRF2-activated ESCC-like lesions. In contrast, while squamous-cell-specific deletion of KEAP1 induces similar NRF2 hyperactivation, the loss of KEAP1 combined with expression of TRP53R172H does not elicit the formation of ESCC-like lesions. Instead, KEAP1-deleted cells disappear from the esophageal epithelium over time. These findings demonstrate that, while cellular NRF2 levels are similarly …

Digestion

Corresponding Author: Takeshi Kanno Telephone: 81-22-717-7171, Fax: 81-22-717-7177 E-mail address: kanno. takeshi@ med. tohoku. ac. jp

Digestive Endoscopy

Objectives Narrow light observation is currently recommended as an alternative to Lugol chromoendoscopy (LCE) to detect esophageal squamous cell carcinoma (ESCC). Studies revealed little difference in sensitivity between the two modalities in expert settings; however, these included small numbers of cases. We aimed to determine whether blue light imaging (BLI) without magnification is satisfactory for preventing misses of ESCC. Methods This was a post‐hoc analysis of a multicenter randomized controlled trial targeting patients at high risk of ESCC in expert settings. In this study, BLI without magnification followed by LCE was performed. The evaluation parameters included: (i) the diagnostic abilities of ESCC; (ii) the endoscopic characteristics of lesions with diagnostic differences between the two modalities; and (iii) the color difference between cancerous and noncancerous areas in BLI and LCE. Results …

Diagnostics

For pancreatic masses, an evaluation of their vascularity using contrast-enhanced ultrasonography can help improve their characterization. This study was designed to evaluate the utility and safety of contrast-enhanced transabdominal ultrasonography (CE-TUS) and endoscopic ultrasonography (CE-EUS) in the diagnosis of pancreatic masses including solid or cystic masses. This multi-center comparative open-label superiority study is designed to compare Plain (P)-TUS/EUS alone with P-TUS/P-EUS plus CE-TUS/CE-EUS. Three hundred and one patients with a total of 232 solid pancreatic masses and 69 cystic masses were prospectively enrolled. The primary endpoints are to compare the diagnostic accuracy between P-TUS/P-EUS alone and P-TUS/P-EUS plus CE-TUS/CE-EUS for both the TUS and EUS of solid pancreatic masses, and to compare the diagnostic accuracy between P-EUS alone and P-EUS plus CE-EUS in cystic pancreatic masses. The secondary endpoints are to compare the diagnostic sensitivity and specificity of P-TUS/P-EUS alone and P-TUS/P-EUS plus CE-TUS/CE-EUS for pancreatic solid/cystic masses, and the accuracy of P-TUS alone and P-TUS plus CE-TUS for pancreatic cystic masses. Other secondary endpoints included comparing the diagnostic sensitivity, specificity, and accuracy of CE-TUS, CE-EUS and CE-computed tomography (CT) for solid/cystic pancreatic masses. The safety, degree of effective enhancement, and diagnostic confidence obtained with CE-TUS/CE-EUS will also be assessed.

Gastroenterology Insights

Since linked color imaging (LCI) has been reported to increase the color differences in Barrett’s esophageal adenocarcinoma (BA) compared to white light imaging (WLI), a comparison of the visibility scores of various imaging techniques for BA is warranted to determine best practice standards. This study is to clarify the role of LCI, blue light imaging (BLI), and WLI in the evaluation of BA. A group of 19 endoscopists, comprised of 6 experts and 13 trainees, evaluated the visibility of WLI, BLI, and LCI images in 21 superficial BA cases. Visibility scores were compared between WLI, BLI, and LCI. Visibility scores were also evaluated for lesion morphology, background Barrett’s mucosa, and circumferential location. The visibility scores of experts and trainees were analyzed for comparison. The visibility scores of LCI and BLI were 3.83 and 3.31, respectively, compared to three points for WLI. The visibility of LCI was better than that of WLI regardless of lesion morphology, color, background Barrett’s mucosa, and circumferential location. The LCI improved visibility in BA more than the WLI for both experts and trainees. LCI improved the visibility of BA independent of lesion morphology, color, background Barrett’s mucosa, circumferential location, and the endoscopist’s experience.

Journal of Gastroenterology

BackgroundThe branched-chain amino acids (BCAAs) to tyrosine (Tyr) ratio (BTR) test is used to evaluate the progression of chronic liver disease (CLD). However, the differences across sex, age, body mass index (BMI) and etiologies are still unclear.MethodsWe retrospectively reviewed data from 2,529 CLD cases with free amino acids (FAAs) in peripheral blood from four hospitals and 16,421 general adults with FAAs data from a biobank database. In total, 1,326 patients with CLD (covering seven etiologies) and 8,086 healthy controls (HCs) were analyzed after exclusion criteria. We investigated the change of BTR in HCs by sex, age and BMI and then compared these to patients divided by modified ALBI (mALBI) grade after propensity score matching.ResultsBTR is significantly higher in males than females regardless of age or BMI and decreases with aging in HCs. In 20 types of FAAs, 7 FAAs including BCAAs …

Internal Medicine

Objective The use of a proton pump inhibitor (PPI) reduces rebleeding and mortality in patients with upper gastrointestinal bleeding (UGIB). Vonoprazan is a novel oral agent with strong and sustained acid-inhibitory activity. We clarified the effect of vonoprazan compared with oral PPIs in such patients.Methods We analyzed the Diagnosis Procedure Combination database. The primary outcome was rebleeding, and secondary outcomes were in-hospital mortality and in-hospital mortality after rebleeding. Propensity score matching was performed to balance the comparison groups, and logistic regression analyses were used to compare the outcomes between vonoprazan and oral PPIs.

Clinical Gastroenterology and Hepatology

Background & AimsDespite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs.MethodsIn this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the WHO 2019 classification. Overall, 1,490 patients met the eligibility criteria, and 1,014 were included in the analysis cohort.ResultsIn the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1 …

Cancer Medicine

Background Sedentary behaviours have been associated with increased risks of some common cancers in epidemiological studies; however, it is unclear if these associations are causal. Methods We used univariable and multivariable two‐sample Mendelian randomisation (MR) to examine potential causal relationships between sedentary behaviours and risks of breast, colorectal and prostate cancer. Genetic variants associated with self‐reported leisure television watching and computer use were identified from a recent genome‐wide association study (GWAS). Data related to cancer risk were obtained from cancer GWAS consortia. A series of sensitivity analyses were applied to examine the robustness of the results to the presence of confounding. Results A 1‐standard deviation (SD: 1.5 h/day) increment in hours of television watching increased risk of breast cancer (OR per 1‐SD: 1.15, 95% confidence …

Cancer Medicine

Background This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Methods Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow‐up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non‐users were those who had not used any statins. PCa‐related mortality was …

Cancer Medicine

Background It has been shown that tumor microenvironment (TME) hydroxyapatite (HAP) is typically associated with many malignancies and plays a role in tumor progression and growth. Additionally, acidosis in the TME has been reported to play a key role in selecting for a more aggressive tumor phenotype, drug resistance and desensitization to immunotherapy for many types of cancers. TME‐HAP is an attractive target for tumor detection and treatment development since HAP is generally absent from normal soft tissue. We provide strong evidence that dissolution of hydroxyapatite (HAP) within the tumor microenvironment (TME‐HAP) using a novel therapeutic can be used to kill cancer cells both in vitro and in vivo with minimal adverse effects. Methods We developed an injectable cation exchange nano particulate sulfonated polystyrene solution (NSPS) that we engineered to dissolve TME‐HAP …

Cancer Medicine

Background The purpose of this study was to investigate associations between self‐reported distress (anxiety/depression) and satisfaction with and desire for virtual follow‐up (VFU) care among cancer patients during and beyond the COVID‐19 pandemic. Methods Breast and prostate cancer patients receiving VFU at an urban cancer centre in Toronto, Canada completed an online survey on their sociodemographic, clinical, and technology, characteristics and experience with and views on VFU. EQ5D‐5 L was used to assess distress. Statistical models adjusted for age, gender, education, income and Internet confidence. Results Of 352 participants, average age was 65 years, 48% were women,79% were within 5 years of treatment completion, 84% had college/university education and 74% were confident Internet users. Nearly, all (98%) had a virtual visit via phone and 22% had a virtual visit via video. The …

Cancer medicine

IntroductionExisting approaches in cancer survivorship care delivery have proven to be insufficient to engage primary care. This study aimed to identify stakeholder-informed priorities to improve primary care engagement in breast cancer survivorship care.MethodsExperts in U.S. cancer survivorship care delivery were invited to participate in a 4-round online Delphi panel to identify and evaluate priorities for defining and fostering primary care's engagement in breast cancer survivorship. Panelists were asked to identify and then assess (ratings of 1-9) the importance and feasibility of priority items to support primary care engagement in survivorship. Panelists were asked to review the group results and reevaluate the importance and feasibility of each item, aiming to reach consensus.ResultsRespondent panelists (n = 23, response rate 57.5%) identified 31 priority items to support survivorship care. Panelists …

Cancer Medicine

Background Aberrant Notch signaling pathway has been related with the tumorigenesis in head and neck region, involving oral cavity. Here, we report the correlation between mutations in the Notch signaling pathway and CD8+ T‐cell infiltration via PD‐L1, which lead to enhanced antitumor immunity and may target for immune‐checkpoint inhibitors (ICIs) therapy. Methods This retrospective study analyzed the results of immunohistochemical staining for PD‐L1 and CD8+ T‐cell infiltration in 10 patients and whole‐exome sequencing (WES) was conducted on five of these patients to identify frequently mutated genes. Results Four of 10 patients were positive for PD‐L1 and CD8+ T. By analyzing WES in three of these four patients, we notably identified the mutations of NOTCH1, FBXW7, and noncoding RNA intronic mutation in NOTCH2NLR in two of these three patients. This study may enable better selection of …

Cancer Medicine

Objective Examine the influence of household income on health‐related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). Design Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. Exposure Household income was self‐reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. Outcome Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. Result Children with AML (n= 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean±SD: 76.0±14 household income< 25,000vs.59.9±17income≥ 75,000; adjusted mean difference: 11.2, 95% CI: 2.2–20.2). Seven percent of …

Cancer Medicine

Background Molecular testing is critical to guiding treatment approaches in patients with metastatic non‐small cell lung cancer (mNSCLC), with testing delays adversely impacting the timeliness of treatment decisions. Here, we aimed to evaluate the time from initial mNSCLC diagnosis to treatment decision (TTD) following implementation of in‐house EGFR, ALK, and PD‐L1 testing at our institution. Methods We conducted a retrospective chart review of 165 patients (send‐out testing, n = 92; in‐house testing, n = 73) with newly diagnosed mNSCLC treated at our institution. Data were compared during the send‐out (March 2017–May 2019) and in‐house (July 2019–March 2021) testing periods. We performed a detailed workflow analysis to provide insight on the pre‐analytic, analytic, and post‐analytic intervals that constituted the total TTD. Results TTD was significantly shorter with in‐house testing (10 days …

Cancer Medicine

Purpose Co‐creation, characterised by artists and patients creating a joint work of art, may support patients with the integration of life events, such as living with cancer, into their life story. In the process of co‐creation, resonance relationships between patients, artists and material may evolve that support such integration. Using the framework of resonance theory, we aim to investigate if and how patients move through the three phases of resonance during a process of co‐creation and explore the role of uncontrollability in this process. Methods Ten patients who received cancer treatment with palliative intent completed co‐creation processes, which were audio recorded. These recordings were imported in Atlas‐Ti and analysed by applying content analysis. We searched for the three phases of resonance, Being affected, touched and moved; Self‐efficacy and responding; Adaptive transformation. We additionally …

Cancer Medicine

Background Non‐Hodgkin lymphoma (NHL) accounts for 90% of all malignant lymphomas. This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of NHL by sex, age, and country. Methods Data from 185 countries globally were used for analysis. NHL incidence and mortality were collected via the GLOBOCAN (2020), CI5 series I‐X, WHO mortality database, the Nordic Cancer Registries, and the SEER Program. The WHO Global Health Observatory provided country‐level, age‐standardized prevalence of lifestyle and metabolic risk factors. Trends were examined and reported based on average annual percentage change (AAPC) calculated using Joinpoint regression analysis. Incidence and AAPC are based on data for the last 10 years across countries. Results Globally, age‐standardized incidence and mortality rates for NHL were recorded at 5.8 and 2.6 per …

Cancer Medicine

Background Older cancer survivors often value quality of life (QOL) over survival. Life‐space mobility (LSM), defined as the individual's spatial geographic mobility range, is an important QOL indicator in older adults with chronic illnesses; however, this relationship is unexplored in older cancer survivors. Methods We examined the longitudinal associations and causal relationships between LSM and QOL in 153 older cancer survivors (≥65 years) from the University of Alabama at Birmingham (UAB) Study of Aging. LSM was assessed using the UAB Life‐Space Assessment‐Composite score (LSA‐C), and QOL was assessed by the SF‐12 Mental Component Score (MCS12) and Physical Component Score (PCS12) at 0 (study entry), 6, 18, 36, 54, and 72 months. We examined the causal relationship between LSM and QOL using a cross‐lagged panel model (CLPM). Results The cohort (n = 153) was 76 …

Cancer Medicine

Background Shortness of breath occurs in 10%–70% of oncology patients. Very little is known about interindividual variability in its severity and distress and associated risk factors. Using latent profile analyses (LPAs), purpose was to identify subgroups of patients with distinct severity and distress profiles for shortness of breath as single symptom dimensions. In addition, a joint LPA was done using patients' severity AND distress ratings. For each of the three LPAs, differences among the shortness of breath classes in demographic, clinical, symptom, stress, and resilience characteristics were evaluated. Methods Patients completed ratings of severity and distress from shortness of breath a total of six times over two cycles of chemotherapy. All of the other measures were completed at enrollment (i.e., prior to the second or third cycle of chemotherapy). Separate LPAs were done using ratings of severity and distress, as …

Cancer Medicine

Background The need for new therapies to improve survival and outcomes in pediatric oncology along with the lack of approval and accessible clinical trials has led to “out‐of‐trial” use of innovative therapies. We conducted a retrospective analysis of requests for innovative anticancer therapy in Canadian pediatric oncology tertiary centers for patients less than 30 years old between 2013 and 2020. Methods Innovative therapies were defined as cancer‐directed drugs used (a) off‐label, (b) unlicensed drugs being used outside the context of a clinical trial, or (c) approved drugs with limited evidence in pediatrics. We excluded cytotoxic chemotherapy, cellular products, and cytokines. Results We retrieved data on 352 innovative therapy drug requests. Underlying diagnosis was primary CNS tumor 31%; extracranial solid tumor 37%, leukemia/lymphoma 22%, LCH 2%, and plexiform neurofibroma 6%. RAS/MAP …

Cancer medicine

Background We examined the awareness, interest, and information sources relating to cannabis use for cancer management (including management of cancer symptoms and treatment‐related side effects) and determined factors associated with cancer survivors' awareness and interest in learning about cannabis use for cancer management. Methods This was a cross‐sectional study of adult cancer survivors (N = 1886) receiving treatment at a comprehensive cancer center. Weighted prevalence and multivariable logistic regression analyses were conducted. Results Among cancer survivors, 88% were aware and 60% were interested in learning about cannabis use for cancer management. Common sources of information to learn about cannabis use for cancer management were cancer doctors/nurses (82%), other patients with cancer (27%), websites/blogs (26%), marijuana stores (20%), and family/friends …

Cancer medicine

IntroductionExisting approaches in cancer survivorship care delivery have proven to be insufficient to engage primary care. This study aimed to identify stakeholder-informed priorities to improve primary care engagement in breast cancer survivorship care.MethodsExperts in U.S. cancer survivorship care delivery were invited to participate in a 4-round online Delphi panel to identify and evaluate priorities for defining and fostering primary care's engagement in breast cancer survivorship. Panelists were asked to identify and then assess (ratings of 1-9) the importance and feasibility of priority items to support primary care engagement in survivorship. Panelists were asked to review the group results and reevaluate the importance and feasibility of each item, aiming to reach consensus.ResultsRespondent panelists (n = 23, response rate 57.5%) identified 31 priority items to support survivorship care. Panelists …

Cancer Medicine

Background Treatments for multiple myeloma (MM) have evolved over time and improved MM survival. While racial differences in MM treatment and prognosis between non‐Hispanic African American (NHAA) and non‐Hispanic White (NHW) patients are well‐established, it is unclear whether they have persisted after the introduction of novel agents. Methods Using the Surveillance, Epidemiology, and End Results‐Medicare linked database, our study investigated racial difference in the receipt of treatment within 1 year following diagnosis and assessed survival outcomes among Medicare beneficiaries (≥66 years) diagnosed with MM from 2007 to 2017. We applied multivariable Cox proportional hazards models to estimate the association between race and survival and presented hazard ratios (HRs). Results Of 2094 NHAA and 11,983 NHW older patients with MM, 59.5% and 64.8% received treatment …

Cancer medicine

Background Estimation of prognosis of oral squamous cell carcinoma (OSCC) is inaccurate prior to surgery, only being effected following subsequent pathological analysis of the primary tumour and excised lymph nodes. Consequently, a proportion of patients are overtreated, with an increase in morbidity, or undertreated, with inadequate margins and risk of recurrence. We hypothesise that it is possible to accurately characterise clinical outcomes from infrared spectra arising from diagnostic biopsies. In this first step, we correlate survival with IR spectra derived from the primary tumour. Methods Infrared spectra were collected from tumour tissue from 29 patients with OSCC and subject to classification modelling. Results The model had a median AUROC of 0.89 with regard to prognosis, a median specificity of 0.83, and a hazard ratio of 6.29 in univariate Cox proportional hazard modelling. Conclusion The data …

Cancer Medicine

Background Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non‐drinker and non‐smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. Methods The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic …

Cancer Medicine

Background and Purpose Colorectal cancer progression from adenoma to cancer is a time‐intensive process; however, the interaction between normal fibroblasts (NFs) with early colorectal tumors, such as adenomas, remains unclear. Here, we analyzed the response of the microenvironment during early tumorigenesis using co‐cultures of organoids and NFs. Materials and Methods Colon normal epithelium, adenoma, cancer organoid, and NFs were established and co‐cultured using Transwell inserts. Microarray analysis of NFs was performed to identify factors expressed early in tumor growth. Immunostaining of clinical specimens was performed to localize the identified factor. Functional analysis was performed using HCT116 cells. Serum DKK1 levels were measured in patients with colorectal cancer and adenoma. Results Colorectal organoid–NF co‐culture resulted in increased organoid diameter and cell …

Cancer Medicine

Background Although oncology clinical practice guidelines recognize the need and benefits of exercise, the implementation of these services into cancer care delivery remains limited. We developed and evaluated the impact of a clinically integrated 8‐week exercise and education program (CaRE@ELLICSR). Methods We conducted a mixed methods, prospective cohort study to examine the effects of the program. Each week, participants attended a 1‐h exercise class, followed by a 1.5‐h education session. Questionnaires, 6‐min walk tests (6MWT), and grip strength were completed at baseline (T0), 8 weeks (T1), and 20 weeks (T2). Semi‐structured interviews were conducted with a sub‐sample of participants about their experience with the program. Results Between September 2017 and February 2020, 277 patients enrolled in the program and 210 consented to participate in the research study. The mean …