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Objective: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. Design: Prospective cohort study. Subjects: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. Results: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14–1.46, P for trend 0.09) for milk and 0.37 (95% CI=0.12–1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI=0.08–1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI=1.00–4.28). Conclusions: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. Sponsorship: This study was supported by a grant from the Swedish Cancer Foundation. European Journal of Clinical Nutrition (2001) 55, 1000–1007

Exosomes are an important group of extracellular vesicles that transfer several kinds of biomolecules and facilitate cell-cell communication. The content of exosomes, particularly the amounts of microRNA (miRNAs) inside these vesicles, demonstrates a disease-specific pattern reflecting pathogenic processes and may be employed as a diagnostic and prognostic marker. miRNAs may enter recipient cells through exosomes and generate a RISC complex that can cause degradation of the target mRNAs or block translation of their corresponding proteins. Therefore, exosome-derived miRNAs constitute an important mechanism of gene regulation in recipient cells. The miRNA content of exosomes can be used as an important tool in the detection of diverse disorders, particularly cancers. This research field has an important situation in cancer diagnosis. In addition, exosomal microRNAs offer a great deal of promise in the treatment of human disorders. However, there are still certain challenges to be resolved. The most important challenges are as follow: the detection of exosomal miRNAs should be standardized, exosomal miRNAs-associated studies should be conducted in large number of clinical samples, and experiment settings and detection criteria should be consistent across different labs. The goal of this article is to present an overview of the effects of exosome-derived microRNAs on a variety of diseases, including gastrointestinal, pulmonary, neurological, and cardiovascular diseases, with a particular emphasis on malignancies.

Chondroblastoma, a rare benign bone tumor, is typically found in the epiphysis of long bones, with hand involvement being particularly uncommon. We present a case of an 11-year-old female with chondroblastoma involving the fourth distal phalanx of the hand. Imaging revealed a lytic, expansile lesion with sclerotic margins and no soft tissue component. A preoperative differential diagnosis included intraosseous glomus tumor, epidermal inclusion cyst, enchondroma, and chronic infection. The patient underwent open surgical biopsy and curettage for both diagnostic and treatment purpose. The final histopathologic diagnosis was chondroblastoma.

OBJECTIVES: 'Overweight and obesity' is the second biggest preventable cause of cancer after smoking. In 2018, Cancer Research UK launched an awareness raising campaign about the link between overweight and obesity and cancer risk. This study aimed to evaluate the reach and impact of the campaign. STUDY DESIGN: This study was a repeated cross-sectional online survey. METHODS: The campaign consisted of six elements including the main message that 'Obesity is a cause of cancer'. UK adults and Members of Parliament (MPs) were surveyed before the campaign (W1; n = 2124 and n = 151), 1 month (W2; n = 2050 and n = 151) and 3 months after the campaign (W3; n = 2059 and MPs not surveyed). Outcome measures were campaign reach, awareness of overweight and obesity as risk factors for cancer, attitudes towards individuals who are overweight or obese, support for policies to reduce obesity and reactions to the campaign. RESULTS: Overall, 76.2% of MPs and just under half of the public (47.5% in W2 and 36.8% in W3) reported having seen the campaign. Unprompted awareness of obesity as a risk factor increased among the public from 17.1% at W1 to 43.3% in W2 (odds ratio 3.71, 95% confidence interval 3.18-4.33) and 30.3% in W3 (odds ratio 2.11, 95% confidence interval 1.80-2.47). A similar pattern was seen for prompted awareness and among MPs. There were no consistent changes in attitudes towards overweight individuals or support for policies to reduce obesity. CONCLUSIONS: This evaluation suggests that the campaign achieved the primary objective of increasing awareness of the link between obesity and cancer without increasing negative attitudes towards individuals who are overweight or obese.

BackgroundCurrent data on the association between tumor size, subtype, and metastases, and thresholds for intervention, for renal cell carcinoma (RCC), are largely based on single-center nephrectomy registries that may under-represent those presenting with metastatic disease.ObjectiveWe sought to assess tumor size and histologic subtype in relation to metastatic status at presentation for patients with RCC.Design setting and participantsUsing Surveillance, Epidemiology and End Results cancer registry data, we identified patients with a diagnosis of RCC made between 2004 and 2019, and a known size of primary tumor. We used nodal and metastatic TNM staging to assess metastatic disease at presentation.Outcome measurements and statistical analysisWe report the proportion of metastatic disease across varying tumor sizes for clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) RCC. We also examine sarcomatoid RCC and RCC with sarcomatoid features (sarcRCC). Logistic regression models were used to model the likelihood of metastatic disease for each histologic subtype.Results and limitationsOf 181096 RCC patients included, 23829 had metastatic disease. For any RCC, metastatic rates of 3.6%, 13.1%, 30.3%, and 45.1% were observed for tumors ≤4, 4-≤7, 7-≤10, and >10 cm, respectively. Metastatic rates of chRCC were low at even large sizes, 11.0% at >10 cm. In contrast, sarcRCC had high metastatic rates at all sizes, 27.1% at ≤4 cm. Metastatic rates for ccRCC and pRCC increased steadily above 3 cm. For any RCC and each evaluated subtype, tumor size was found to be associated with metastatic disease on logistic regression (p&nbsp

The PROpel trial assessed the combination of olaparib+abiraterone acetate (AA) plus prednisone and androgen deprivation therapy (ADT) versus AA plus prednisone and ADT alone as first-line treatment for metastatic castration-resistant prostate cancer (mCPRP). To contextualize the progression free survival (PFS) benefit in PROpel, we performed a systematic review and quasi-individual patient data network meta-analysis on randomized controlled trials of first-line hormonal treatments for mCPRC. Meta-analysis was performed for the PROpel control arm and PREVAIL (enzalutamide) and COU-AA-302 (AA) treatment arms. Kaplan-Meier PFS curves were digitally reconstructed and differences in restricted mean survival time (ΔRMST) were computed. Combination therapy yielded longer PFS (24-mo ΔRMST 1.5 mo, 95% confidence interval 0.6-2.4) in comparison to novel hormonal treatments alone. However, the lack of mature overall survival data, higher complication rates, and higher health care costs are limitations of combination therapy. Ultimately, combining treatments, rather than molecularly targeted sequencing in cases of failure, might not be justified in unselected patients with mCRPC.Patient summaryA recent trial showed that for metastatic prostate cancer that does not respond to hormone treatment, combined therapy with two drugs (olaparib and abiraterone) may prolong survival free from cancer progression. We included these data in an analysis of three trials that confirmed a small benefit. This combination approach has higher complication rates and is more expensive, and longer-term results for overall survival are needed.

Cancer ranks among the five leading causes of death in almost all countries and has important repercussions for individual and public health, the healthcare system and society in general. Obesity increases the incidence of many types of cancer, but growing evidence suggests that physical activity may decrease risk for developing a variety of obesity-related cancer types, and in some cases also, improve cancer prognosis and mortality rates. This review summarizes recent evidence on the effect of physical activity on obesity-related cancer prevention and survival. For some cancers, including breast, colorectal, and endometrial cancer, there is strong evidence for a preventative effect of exercise, but for many others, including gallbladder and kidney cancer, and multiple myeloma, evidence is inconsistent or largely lacking. Though many potential mechanisms have been proposed to explain the onco-protective effect of exercise, including improved insulin sensitivity, alterations in sex hormone availability, improved immune function and inflammation, myokine secretion, and modulation of intracellular signaling at the level of AMP kinase, the exact mechanism(s) of action within each cancer subtype remains poorly defined. Overall, a deeper understanding of how exercise can help against cancer and of the exercise parameters that can be tweaked to optimize exercise prescription is necessary and should be the subject of future investigation.

The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and cancer progression. MAPK-pathway upregulation is the main event in the development and progression of human cancer, including melanoma and recent studies have shown that MALAT1 has a significant impact on the regulation of gene and protein expression in the MAPK pathway. However, the role of MALAT1 in regulation of gene and protein expression of the MAPK-pathway kinases RAS, RAF, MEK and ERK in melanoma is largely unknown. We demonstrate the impacts of antisense oligonucleotide (ASO)-based MALAT1-inhibition on MAPK-pathway gene regulation in melanoma. Our results showed that MALAT1-ASO treatment decreased BRAF RNA expression and protein levels, and MALAT1 had increased correlation with MAPK-pathway associated genes in melanoma patient samples compared to healthy skin. Additionally, drug-induced MAPK inhibition upregulated MALAT1-expression, a finding that resonates with a paradigm of MALAT1-expression presented in this work: MALAT1 is downregulated in melanoma and other cancer types in which MALAT1 seems to be associated with MAPK-signaling, while MALAT1-ASO treatment strongly reduced the growth of melanoma cell lines, even in cases of resistance to MEK inhibition. MALAT1-ASO treatment significantly inhibited colony formation in vitro and reduced tumor growth in an NRAS-mutant melanoma xenograft mouse model in vivo, while showing no aberrant toxic side effects. Our findings demonstrate new insights into MALAT1-mediated MAPK-pathway gene regulation and a paradigm of MALAT1 expression in MAPK-signaling-dependent cancer types. MALAT1 maintains essential oncogenic functions, despite being downregulated.

Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy1,2. This is mediated in part by a complex tumour microenvironment3, low vascularity4, and metabolic aberrations5,6. Although altered metabolism drives tumour progression, the spectrum of metabolites used as nutrients by PDA remains largely unknown. Here we identified uridine as a fuel for PDA in glucose-deprived conditions by assessing how more than 175 metabolites impacted metabolic activity in 21 pancreatic cell lines under nutrient restriction. Uridine utilization strongly correlated with the expression of uridine phosphorylase 1 (UPP1), which we demonstrate liberates uridine-derived ribose to fuel central carbon metabolism and thereby support redox balance, survival and proliferation in glucose-restricted PDA cells. In PDA, UPP1 is regulated by KRAS–MAPK signalling and is augmented by nutrient restriction. Consistently, tumours expressed high UPP1 compared with non-tumoural tissues, and UPP1 expression correlated with poor survival in cohorts of patients with PDA. Uridine is available in the tumour microenvironment, and we demonstrated that uridine-derived ribose is actively catabolized in tumours. Finally, UPP1 deletion restricted the ability of PDA cells to use uridine and blunted tumour growth in immunocompetent mouse models. Our data identify uridine utilization as an important compensatory metabolic process in nutrient-deprived PDA cells, suggesting a novel metabolic axis for PDA therapy.

Background and Objectives: Glucose metabolism alterations are very common in solid pancreatic lesions, particularly in pancreatic cancer. Similarly, diabetes and especially new-onset diabetes (NOD) have been associated with the malignant transformation of pancreatic cysts. We aimed to assess the prevalence and relevant associations of glycemic abnormalities in pancreatic cystic lesions (PCLs) in a retrospective analysis. Materials and Methods: We retrospectively recruited all patients who underwent endoscopic ultrasound for a PCL over a period of 36 months (January 2018 to December 2021). Final diagnosis was set by means of tissue acquisition, surgery, follow-up, or board decision. Demographic and clinical data, laboratory workup, and imaging features were extracted from the patients’ charts according to a predefined protocol. We considered fasting blood glucose (FBG) and HbA1c values and stratified the patients as nondiabetic (FBG ≤ 99 mg/dL, HbA1c ≤ 5.6%, no history of glycemic abnormalities), prediabetic (FBG 100–125 mg/dL, HbA1c 5.7–6.4%), or diabetic (long-lasting diabetes or NOD). Results: Altogether, 81 patients were included, with a median age of 66 years, and 54.3% of them were male. The overall prevalence of fasting hyperglycemia was 54.3%, comprising 34.6% prediabetes and 22.2% diabetes, of which 16.7% had NOD. The mean FBG and HbA1c levels were higher in malignant and premalignant PCLs (intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), cystadenocarcinoma, and cystic neuroendocrine tumor) compared to the benign lesions (pseudocysts, walled-off necrosis, and serous cystadenoma): 117.0 mg/dL vs. 108.3 mg/dL and 6.1% vs. 5.5%, respectively. Conclusions: Hyperglycemia and diabetes are common in PCLs, with a high prevalence in premalignant and malignant cysts. Screening and follow-up for glycemic abnormalities should be routinely conducted for PCLs, as they can contribute to a tailored risk assessment of cysts.

OBJECTIVES: In biomedical research, spin is the overinterpretation of findings, and it is a growing concern. To date, the presence of spin has not been evaluated in prognostic model research in oncology, including studies developing and validating models for individualized risk prediction. STUDY DESIGN AND SETTING: We conducted a systematic review, searching MEDLINE and EMBASE for oncology-related studies that developed and validated a prognostic model using machine learning published between 1st January, 2019, and 5th September, 2019. We used existing spin frameworks and described areas of highly suggestive spin practices. RESULTS: We included 62 publications (including 152 developed models; 37 validated models). Reporting was inconsistent between methods and the results in 27% of studies due to additional analysis and selective reporting. Thirty-two studies (out of 36 applicable studies) reported comparisons between developed models in their discussion and predominantly used discrimination measures to support their claims (78%). Thirty-five studies (56%) used an overly strong or leading word in their title, abstract, results, discussion, or conclusion. CONCLUSION: The potential for spin needs to be considered when reading, interpreting, and using studies that developed and validated prognostic models in oncology. Researchers should carefully report their prognostic model research using words that reflect their actual results and strength of evidence. ispartof: JOURNAL OF CLINICAL EPIDEMIOLOGY vol:157 pages:120-133 ispartof: location:United States status: published

Healing wounds and cancers present remarkable cellular and molecular parallels, but the specific roles of the healing phases are largely unknown. We developed a bioinformatics pipeline to identify genes and pathways that define distinct phases across the time-course of healing. Their comparison to cancer transcriptomes revealed that a resolution phase wound signature is associated with increased severity in skin cancer and enriches for extracellular matrix-related pathways. Comparisons of transcriptomes of early- and late-phase wound fibroblasts vs skin cancer-associated fibroblasts (CAFs) identified an "early wound" CAF subtype, which localizes to the inner tumor stroma and expresses collagen-related genes that are controlled by the RUNX2 transcription factor. A "late wound" CAF subtype localizes to the outer tumor stroma and expresses elastin-related genes. Matrix imaging of primary melanoma tissue microarrays validated these matrix signatures and identified collagen- vs elastin-rich niches within the tumor microenvironment, whose spatial organization predicts survival and recurrence. These results identify wound-regulated genes and matrix patterns with prognostic potential in skin cancer., Matrix Biology, 119, ISSN:0945-053X, ISSN:1569-1802

Photodynamic therapy (PDT) is an interesting and promising approach to tackle a broad spectrum of cancer types. With the combination of a photosensitizer, light and oxygen, PDT achieves a unique selectivity by the production of localized reactive oxygen species (ROS) inside cells, which leads to their destruction. In addition, the luminescence properties of photosensitizers can be exploited to develop imaging tools. Unfortunately, the cancer selectivity and homogeneity of most photosensitizers are frequently limiting the performances of PDT and cancer detection/characterization by luminescence imaging. Consequently, our study aims to use cellulose nanocrystals to transport and deliver radiolabeled photo-responsive metalla-assemblies to create a new generation of theranostic agents for PDT and imaging applications. The synthesis, structural characterization, cytotoxicity evaluation, and in vivo biodistribution imaging of the compounds are presented. The best candidates show excellent biological activity and selectivity towards ovarian carcinoma cell line (A2780), cisplatin resistant ovarian carcinoma cell line (A2780cis) versus normal human embryonic kidney cells (HEK293T), as well as efficient imaging properties, suggesting a potential use as multimodal theranostic agents.

ObjectiveThe objective of this formative study was to gather women's perspectives in the design and communication modalities of a health kiosk set within a Planned Parenthood setting to promote patient education about the Human papillomavirus (HPV) and to motivate uptake of the HPV vaccine.MethodsTwenty-four women aged 18-35 participated in in-depth one-on-one interviews at a Planned Parenthood health center, which were analyzed in code-associated categories using NVivo11 Pro.ResultsMost women showed receptivity to using an on-site health kiosk, as well as QR codes linked to text messages, to receive HPV-related health information outside of the clinic setting and reminders. Participants provided suggestions for kiosk design and communication modalities.ConclusionsAmong low-income women we interviewed at Planned Parenthood, increasing HPV vaccination rates necessitates engaging digital health tools which incorporate both the preferences and needs of vulnerable populations.InnovationDesigning a point-of-service health kiosk that 1) draws on user preferences early in the design phase, 2) integrates multiple communication technologies, and 3) disseminates culturally grounded HPV vaccination decisions narratives that are tailored to vaccination awareness level is a promising approach in reducing barriers to HPV vaccine education and vaccine uptake among low-income women at safety-net clinics.

This is a case of a young woman who developed neurological and psychiatric symptoms 3 days after resection of an immature teratoma. She was diagnosed with anti-NMDA receptor encephalitis via positive serum antibody titres, which was later confirmed with cerebrospinal fluid antibody titres. Given her cancer diagnosis, she underwent treatment with bleomycin, etoposide and cisplatin chemotherapy in addition to 5 days of high-dose steroids (1 g of intravenous methylprednisolone) for the encephalitis. This treatment regimen led to significant clinical improvement 3 weeks after completion of one cycle of chemotherapy.

Modulation of proteasome function by pharmacological interventions and molecular biology tools is an active area of research in cancer biology and neurodegenerative diseases. Curcumin (diferuloylmethane) is a naturally occurring polyphenol that affects multiple signaling pathways and known to modulate PKC activities. The therapeutic significance of curcumin is often considered to reside in its anti-inflammatory, antioxidant, anti-angiogenic, or anti-apoptotic properties. However, recent research suggests that the therapeutic efficacy of curcumin may be due to its activity as a potent inhibitor of the proteasome. In this study, we show that both curcumin and its synthetic polyphenolic derivative (didemethylcurcumin), CUIII modulated proteasome activity in a biphasic manner. Curcumin and CUIII increased proteasome activity at nanomolar concentrations but inhibited proteasome activity at micromolar concentrations. Curcumin was more effective than CUIII in relative proteasome activity increase at nanomolar concentrations. Also, curcumin was more effective than CUIII in relative proteasome activity inhibition at micromolar concentration. The docking study was conducted on the 20S proteasome catalytic subunit. Estimated Kd values for curcumin and didemethylcurcumin are 0.0054μM and 1.3167μM, respectively. These values correlate well with the results of the effectiveness of modulation by curcumin compare to CUIII. The small size of CUIII makes its dock to the narrow cavity of the active site, but the binding interaction is not strong compare to curcumin. This study suggests that curcumin and its didemethyl derivative can be used to modulate proteasome activity. This communication implicates the reason why curcumin and its didemethyl derivative can be used to two different disease mechanisms, neurodegeneration, and cancer.

Introduction: Data regarding laterality, focality, or total tumour diameter (TTD) in papillary thyroid cancer (PTC) are limited. We aimed to investigate the impact of focality, TTD, number of tumour foci, or laterality on aggressive features in PTC. Material and methods: Patients were categorized based on maximum tumour diameter (MTD) (≤ 10 vs. > 10 mm), focality, laterality, or the number of tumour foci (1/2/ ≥3). We also categorized the patients as follows: Group 1, unifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 2, multifocal microcarcinoma (MTD ≤ 10/TTD ≤ 10 mm); Group 3, multifocal microcarcinoma (MTD ≤ 10/TTD > 10 mm); Group 4, unifocal macrocarcinoma (MTD > 10/TTD > 10 mm); Group 5, multifocal macrocarcinoma (MTD > 10/TTD > 10 mm). Results: The mean diagnosis age (n = 511) was 44.7 (± 12.7) years, the majority of the patients were < 55 years old (n = 310) and female (n = 416). An increasing number of tumour foci were associated with a higher MTD or TTD, a higher ratio of extrathyroidal extension (ETE), vascular or lymphatic invasion, lymph node metastasis (LNM) or distant metastasis, or the need for radioactive iodine (RAI). There was no difference in the parameters between Group 3 and Group 2, or Group 4. Vascular invasion, American Thyroid Association high risk, LNM at diagnosis, and RAI total dose were higher in Group 5 than in Group 3. Microscopic or macroscopic ETE, T1b, and T4a were positive predictors for recurrence. Male sex, multifocality, number of tumour foci (≥ 3), MTD (> 10 mm), TTD (> 10 mm), Group 5, microscopic or macroscopic ETE, lymphatic or vascular invasion, RAI need, T2, and T4b were positive predictors for LNM. Conclusion: MTD and TTD increase the risk of LNM but not the recurrence in PTC. TTD, multifocality, and bilaterality can be considered risk factors in PTC staging systems and risk calculators.

La gestion des risques professionnels relève de deux aspects : celui de la prévention sur les lieux de travail et celui de l’indemnisation au titre du régime sur les accidents du travail et des maladies professionnelles. Intrinsèquement liées, ces deux démarches sont pourtant régulièrement mises en opposition par différents acteurs du domaine. La présente contribution explore les rapports entre les logiques de prévention et d’indemnisation dans la réglementation française. Présentées comme antagoniques, elles n’en sont pas moins complémentaires. La démonstration s’appuie sur l’étude des cancers professionnels, exemple par excellence qui permet d’interroger les difficultés à relier ces deux aspects., The management of occupational risks can be examined in two aspects: the prevention in the workplace and the compensation program of the accidents and occupational diseases. Intrinsically linked, these two approaches are however regularly put in opposition by different actors in the field. This contribution explores the relationship between the logics of prevention and compensation in the French legislation. Presented as antagonistic, they are no less complementary. The demonstration is based on the study of occupational cancers, an example which par excellence makes it possible to question the difficulties in linking these two aspects.

Cost-effectiveness analyses of new cancer treatments in real-world settings (e.g., post-clinical trials) inform healthcare decision makers about their healthcare investments for patient populations. The results of these analyses are often, though not always, presented with statistical uncertainty. This paper identifies five ways to characterize statistical uncertainty: (1) a 95% confidence interval (CI) for the incremental cost-effectiveness ratio (ICER); (2) a 95% CI for the incremental net benefit (INB); (3) an INB by willingness-to-pay (WTP) plot; (4) a cost-effectiveness acceptability curve (CEAC); and (5) a cost-effectiveness scatterplot. It also explores their usage in 22 articles previously identified by a rapid review of real-world cost effectiveness of novel cancer treatments. Seventy-seven percent of these articles presented uncertainty results. The majority those papers (59%) used administrative data to inform their analyses while the remaining were conducted using models. Cost-effectiveness scatterplots were the most commonly used method (34.3%), with 40% indicating high levels of statistical uncertainty, suggesting the possibility of a qualitatively different result from the estimate given. Understanding the necessity for and the meaning of uncertainty in real-world cost-effectiveness analysis will strengthen knowledge translation efforts to improve patient outcomes in an efficient manner.

Purpose HER2 overexpression has a central role in breast cancer carcinogenesis and is associated with poor prognosis if untreated. Lately, identification of HER2-low breast cancer has been proposed to select patients for novel HER2-directed chemotherapy and includes cancers with immunohistochemistry 1 + or 2 + with negative FISH, encompassing approximately 55–60% of all breast carcinomas. In early-stage breast cancer, the prognostic significance of HER2 low-disease is less well understood, with a particular paucity of data evaluating the prevalence and implications of HER2-low status in invasive lobular carcinoma (ILC). Methods We evaluated 666 stage I-III ILC tumors from a prospectively maintained institutional database, comparing clinicopathologic features and disease-free survival (DFS) using a multivariable Cox proportional hazards model. Results HER2-low status was common in this cohort of patients with ILC, but most clinicopathologic features did not differ between HER2-low and HER2-negative cases. However, when adjusting for tumor size, number of positive nodes, ER/PR status, and local therapy received, patients with HER2-low status had worse disease-free survival (DFS) than those with HER2-negative tumors (hazard ratio 2.0, 95% confidence interval 1.0–4.1, p = 0.05). Conclusion This difference in DFS supports the notion that HER2-low and HER2-negative early stage ILC may differ clinically, despite similar clinicopathologic features. Further investigation into the potential benefit of HER2 targeted therapy in HER2-low early-stage breast cancer, and specifically lobular cancer, is warranted to ensure optimal outcomes in this distinct tumor subtype.

Background Cost-effectiveness is important in the prioritisation between interventions in health care. Exercise is cost-effective compared to usual care during oncological treatment; however, the significance of exercise intensity to the cost-effectiveness is unclear. In the present study, we aimed to evaluate the long-term cost-effectiveness of the randomised controlled trial Phys-Can, a six-month exercise programme of high (HI) or low-to-moderate intensity (LMI) during (neo)adjuvant oncological treatment. Methods A cost-effectiveness analysis was performed, based on 189 participants with breast, colorectal, or prostate cancer (HI: n = 99 and LMI: n = 90) from the Phys-Can RCT in Sweden. Costs were estimated from a societal perspective, and included cost of the exercise intervention, health care utilisation and productivity loss. Health outcomes were assessed as quality-adjusted life-years (QALYs), using EQ-5D-5L at baseline, post intervention and 12 months after the completion of the intervention. Results At 12-month follow-up after the intervention, the total cost per participant did not differ significantly between HI (€27,314) and LMI exercise (€29,788). There was no significant difference in health outcome between the intensity groups. On average HI generated 1.190 QALYs and LMI 1.185 QALYs. The mean incremental cost-effectiveness ratio indicated that HI was cost effective compared with LMI, but the uncertainty was large. Conclusions We conclude that HI and LMI exercise have similar costs and effects during oncological treatment. Hence, based on cost-effectiveness, we suggest that decision makers and clinicians can consider implementing both HI and LMI exercise programmes and recommend either intensity to the patients with cancer during oncological treatment to facilitate improvement of health. Funding agencies: This work was supported by grants from the Swedish Cancer Society; the Swedish Research Council, and the Region Östergötland, Sweden.

ObjectivesThe COVID-19 pandemic placed severe strain on cancer carers resulting in an urgent need for information and support.MethodsThe Santin 2019 6-step co-design model was used to rapidly modify an existing online cancer carers resource. Draft content of a COVID-19 module was created via two workshops and six meetings with an expert advisory team (Step 1). This content was then produced into videoed testimonials (Step 2). A module prototype was reviewed by volunteers (Step 3) and modified based on feedback (Step 4). User-testing occurred via two online feedback sessions (Step 5) and modifications were made (Step 6). All steps were audio recorded, transcribed verbatim and analysed thematically.ResultsA COVID-19 support, and information module was rapidly co-designed by n = 45 stakeholders (n = 11 workshop 1 and 2 (3 carers/14 professionals), n = 6 advisory committee (1 carer/5 professionals), n = 4 video content (1 carer/3 professionals) and n = 24 feedback sessions (5 carers/19 professionals). The module contained vaccination information, infection control and how to manage the psychosocial impact of restrictions. Information was delivered in 4 short videos with links to up-to-date guidance and information services. Participants identified that the module included all key information for carers in an accessible and informative way. The use of videos was viewed as an emotive and reassuring.ConclusionsDuring a global pandemic, cancer carers urgently required tailored information. Co-designed online resources allow service providers to rapidly respond to emerging and unprecedented issues and provide urgent information and support.

Evidence-based practices facilitate the effective delivery of psychological services, yet research on the implementation of evidence-based practices in psychosocial oncology (PSO) is scarce. Responding to this gap, we interviewed a diverse sample of 16 directors of Canadian psychosocial oncology services about (a) how evidence-based practices in psychosocial oncology are being implemented in clinical care and how the service quality is monitored and (b) what are barriers and facilitators to evidence-based practice in psychosocial oncology services? Responses were grouped according to three main themes emerging from the data: screening for distress and referral to PSO services, delivery of evidence-based PSO services, and monitoring of PSO services. Our findings highlight facilitators and barriers to evidence-based practice in psychosocial oncology, which were related to the political, social, economic, and geographic contexts. The stepped care model was identified as a science-informed approach to improve the cost-effectiveness of triage systems and treatment delivery while facilitating more equitable access to services. Other facilitators included electronic screening and referral systems as well as protected time for clinicians to communicate more within their teams and participate in knowledge exchange. High caseloads presented a major barrier to acquiring and implementing evidence-based practices. Recommen–dations include increased support for evidence-based onboarding and continued training as well as for data collection regarding service needs, quality, and quantity to inform service monitoring and advocacy for more financial resources. Our findings are relevant to healthcare decision makers, implementation researchers, as well as service directors and practitioners providing psychosocial oncology care.

PURPOSE Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression. In this study, we compared response to neoadjuvant chemotherapy and survival between patients with TNBC and non-TNBC. PATIENTS AND METHODS Analysis of a prospectively collected clinical database was performed. We included 1,118 patients who received neoadjuvant chemotherapy at M.D. Anderson Cancer Center for stage I-III breast cancer from 1985 to 2004 and for whom complete receptor information were available. Clinical and pathologic parameters, pathologic complete response rates (pCR), survival measurements, and organ-specific relapse rates were compared between patients with TNBC and non-TNBC. RESULTS Two hundred fifty-five patients (23%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates (22% v 11%; P = .034), but decreased 3-year progression-free survival rates ( P < .0001) and 3-year overall survival (OS) rates ( P < .0001). TNBC was associated with increased risk for visceral metastases ( P = .0005), lower risk for bone recurrence ( P = .027), and shorter postrecurrence survival ( P < .0001). Recurrence and death rates were higher for TNBC only in the first 3 years. If pCR was achieved, patients with TNBC and non-TNBC had similar survival ( P = .24). In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC ( P < .0001). CONCLUSION Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival. However, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with non-TNBC, particularly in the first 3 years.

BackgroundMedullary carcinoma (MC) is a recognized histologic subtype of colorectal cancer characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. However, MC originating from the small intestine is exceedingly rare, with only nine cases described in the literature. Based on previous cases, surgical resection is currently the mainstay of treatment for those with localized disease. We report the first case of a patient who presented with unresectable microsatellite instability-high (MSI-H) MC of the duodenum and was instead treated with pembrolizumab.Case descriptionA 50-year-old man with history of adenocarcinoma of the proximal descending colon status post hemicolectomy and adjuvant treatment with chemotherapy and family history of Lynch syndrome presented with abdominal pain for two weeks. Computed tomography (CT) abdomen/pelvis revealed a 10.7 cm by 4.3 cm mass in the mid-portion of the duodenum abutting against the pancreatic head. Esophagogastroduodenoscopy (EGD) demonstrated circumferential, partially obstructing, intrinsic stenosis of the duodenum with ampullary involvement and likely invasion into the pancreatic head and common bile duct. Endoscopic biopsy of the primary tumor revealed poorly differentiated MC. Immunohistochemical staining showed loss of MLH1 and PMS2 expression. Staging with CT chest showed no evidence of disease. Positron emission tomography (PET) scan redemonstrated circumferential duodenal wall thickening and hypermetabolic activity with standardized uptake value (SUV) max of 26.4, as well as PET-avid epigastric, retroperitoneal, and periaortic lymphadenopathy suggestive of metastasis. He was started on pembrolizumab and found to have stable disease on repeat imaging along with significant improvement in symptoms and performance status.ConclusionsDue to the rarity of the tumor, there is no standardized approach to treatment. All patients in previously published cases underwent surgical resection. However, our patient was deemed a poor surgical candidate. Given his previous history of colon cancer and treatment with platinum-based therapy, he qualified for pembrolizumab as first line therapy for his MSI-H tumor. To our knowledge, this is the first report of MC of the duodenum as well as the first MC to be treated with pembrolizumab in the first line setting. In order to corroborate the use of immune checkpoint inhibitors as a treatment option for MC of the colon or small intestine, the aggregation of existing and future case data in this unique patient group is certainly warranted.

Introduction: Cucurbitacins are one of the most important components of Ecballium elaterium. Among the cucurbitacins, Cucurbitacin E was the first to be isolated. This study focused on screening the anticancer and insecticidal potential of Cucurbitacin E by the in-vitro, in-vivo, and in-silico methods. Methods: In the study, toxicity analysis of Cucurbitacin E were determined on HeLa, Caco 2 cancer cell lines and D. melanogaster. While the expression levels of the BAD, BCL-2, AKT-1 and H-purine genes of cancer cell lines were determined, the CG15530, BUFFY, AKT-1 and Purine genes of D. melanogaster were determined by RT-PCR. Besides, molecular docking and dynamic properties of Cucurbitacin E with human and insectoid enzymes were presented in silico. Results: The IC50 value of Cucurbitacin E in the HeLa ovarian and Caco 2 colon cancer cell lines was determined to be 42 ug/ml and 85 ug/ml, respectively. The LC50 and LC99 doses for fruit flies were determined to be 47,693 µg/ml and 133,251 µg/ml, respectively. Gene expression analysis revealed that Cucurbitacin E showed the greatest effect on Purine and AKT-1 genes in D. melanogaster. We analyzed all genes by Western blot, but we did not detect significant changes in genes other than H-purine. In silico studies revealed that the Purine protein of D. melanogaster had the highest bonding energy with Cucurbitacin E as a ligand. Similarly, Cucurbitacin E showed great affinity towards H-purine (-10.2 kcal/mol). Molecular dynamics simulation studies were also performed to determine the stability of the dynamic process. Conclusion: Conclusion: As a result of our in vivo, in vitro and bioinformatic analyzes, it has been seen that Cucurbitacine E is effective against the cancer types and model insect studied.

BackgroundIncreasing legalization of cannabis, in addition to longstanding rates of tobacco use, raises concerns for possible cognitive decrements from secondhand smoke or environmental exposure, although little research exists. We investigate the relation between cognition and secondhand and environmental cannabis and tobacco exposure in youth.MethodsThe Adolescent Brain Cognitive Development (ABCD) Study year 2 follow-up (N= 5580; 48% female) cognitive performance and secondhand or environmental cannabis or tobacco exposure data were used. Principal components analysis identified a global cognition factor. Linear mixed-effects models assessed global cognition and individual cognitive task performance by cannabis and/or tobacco environmental exposure. Sociodemographics and other potential confounds were examined. p values were adjusted using the false discovery rate method.ResultsGlobal cognition was not related to any exposure group after testing corrections and considering confounds. Beyond covariates and family- and site-level factors, secondhand tobacco was related to poorer visual memory (p= .02), and environmental tobacco was associated with poorer visuospatial (p= .02) and language (p= .008) skills. Secondhand cannabis was related to cognition, but not after controlling for potential confounders (p > .05). Environmental cannabis was related to better oral reading (p= .01). Including covariates attenuated effect sizes.ConclusionsSecondhand tobacco exposure was associated with poorer visual memory, while environmental tobacco exposure was related to poorer language and visuospatial skills. Secondhand cannabis was not related to cognition after controlling for sociodemographic factors, but environmental cannabis exposure was related to better reading. Because, to our knowledge, this is the first known study of its kind and thus preliminary, secondhand cannabis should continue to be investigated to confirm results.

Phylogenetic methods are emerging as a useful tool to understand cancer evolutionary dynamics, including tumor structure, heterogeneity, and progression. Most currently used approaches utilize either bulk whole genome sequencing (WGS) or single-cell DNA sequencing (scDNA-seq) and are based on calling copy number alterations and single nucleotide variants (SNVs). Here we explore the potential of single-cell RNA sequencing (scRNA-seq) to reconstruct cancer evolutionary dynamics. scRNA-seq is commonly applied to explore differential gene expression of cancer cells throughout tumor progression. The method exacerbates the single-cell sequencing problem of low yield per cell with uneven expression levels. This accounts for low and uneven sequencing coverage and makes SNV detection and phylogenetic analysis challenging. In this paper, we demonstrate for the first time that scRNA-seq data contains sufficient evolutionary signal and can be utilized in phylogenetic analyses. We explore and compare results of such analyses based on both expression levels and SNVs called from our scRNA-seq data. Both techniques are shown to be useful for reconstructing phylogenetic relationships between cells, reflecting the clonal composition of a tumor. Without an explicit error model, standardized expression values appear to be more powerful and informative than the SNV values at a lower computational cost, due to being a by-product of standard expression analysis. Our results suggest that scRNA-seq can be a competitive alternative or useful addition to conventional scDNA-seq phylogenetic reconstruction. Our results open up a new direction of somatic phylogenetics based on scRNA-seq data. Further research is required to refine and improve these approaches to capture the full picture of somatic evolutionary dynamics in cancer.

A plethora of paraneoplastic syndromes have been reported as remote effects of colorectal carcinoma (CRC). However, there is a dearth of data pertaining to the association of this cancer with demyelinating neuropathies. Herein, we describe the case of a young woman diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment with intravenous immunoglobulins and prednisone did not improve her condition, and her neurological symptoms worsened. Subsequently, she was readmitted with exertional dyspnea, lightheadedness, malaise, and black stools. Colonoscopy revealed a necrotic mass in the ascending colon, which directly invaded the second part of the duodenum. Pathologic results confirmed the diagnosis of locally advanced CRC. Upon surgical resection of the cancer, her CIDP showed dramatic resolution without any additional therapy. Patients with CRC may develop CIDP as a type of paraneoplastic syndrome. Clinicians should remain cognizant of this potential association, as it is of paramount importance for the necessary holistic clinical management.

Hepatocellular carcinoma (HCC) has multiple molecular classes that are associated with distinct etiologies and, besides particular molecular characteristics, that also differ in clinical aspects. We aim to characterize the clinical aspects of alcoholic liver disease-related HCC by a retrospective observational study that included all consequent patients diagnosed with MRI or histologically verified HCC in participating centers from 2010 to 2016. A total of 429 patients were included in the analysis, of which 412 patients (96%) had cirrhosis at the time of diagnosis. The most common etiologies were alcoholic liver disease (ALD) (48.3%), chronic hepatitis C (14.9%), NAFLD (12.6%), and chronic hepatitis B (10%). Patients with ALD-related HCC were more commonly males, more commonly had cirrhosis that was in more advanced stages, and had poorer performance status. Despite these results, no differences were observed in the overall (median 8.1 vs. 8.5 months) and progression-free survival (median 4.9 vs. 5.7 months). ALD-HCC patients within BCLC stage 0–A less frequently received potentially curative treatment as compared to the control HCC patients (62.2% vs. 87.5%, p = 0.017); and in patients with ALD-HCC liver function (MELD score) seemed to have a stronger influence on the prognosis compared to the control group HCC. Systemic inflammatory indexes were strongly associated with survival in the whole cohort. In conclusion, alcoholic liver disease is the most common cause of hepatocellular carcinoma in Slovakia, accounting for almost 50% of cases; and patients with ALD-related HCC more commonly had cirrhosis that was in more advanced stages and had poorer performance status, although no difference in survival between ALD-related and other etiology-related HCC was observed.

Cancer in adolescence is considered a family disease that can have numerous negative psychological consequences for adolescents and the entire household. The aim of this study was to investigate the impact of oncological disease in adolescence, with particular reference to the psychological and post-traumatic consequences for the adolescents themselves and the family system. An explorative case–control study was conducted with 31 adolescents (mean age 18.03 ± 2.799) hospitalised for cancer at IRCCS San Matteo Hospital in Pavia and 47 healthy adolescents (mean age 16.17 ± 2.099). The two samples completed a survey that included sociodemographic information and questionnaires assessing psychological well-being, traumatic effects of the disease, and adequacy of the relationship with parents. 56.7% of oncology adolescents scored below average in psychological well-being, and a small proportion of them fell within the range of clinical concern for anger (9.7%), PTS (12.9%), and dissociation (12.9%). Compared with peers, there were no significant differences. However, in contrast to peers, oncology adolescents showed a strong influence of the traumatic event on the construction of their identity and life perspectives. A significantly positive correlation also emerged between adolescents’ psychological well-being and the relationship with their parents (mothers: r = 0.796; p < 0.01; fathers: r = 0.692; p < 0.01). Our findings highlight how cancer in adolescence could represent a central traumatic event that can shape the identity and life of teenagers who are in an intrinsically delicate and vulnerable stage of life.

Plasma membrane-derived vesicles, also referred to as large extracellular vesicles (lEVs), are implicated in several pathophysiological situations, including cancer. However, to date, no studies have evaluated the effects of lEVs isolated from patients with renal cancer on the development of their tumors. In this study, we investigated the effects of three types of lEVs on the growth and peritumoral environment of xenograft clear cell renal cell carcinoma in a mouse model. Xenograft cancer cells were derived from patients’ nephrectomy specimens. Three types of lEVs were obtained from pre-nephrectomy patient blood (cEV), the supernatant of primary cancer cell culture (sEV) and from blood from individuals with no medical history of cancer (iEV). Xenograft volume was measured after nine weeks of growth. Xenografts were then removed, and the expression of CD31 and Ki67 were evaluated. We also measured the expression of MMP2 and Ca9 in the native mouse kidney. lEVs from kidney cancer patients (cEV and sEV) tend to increase the size of xenografts, a factor that is related to an increase in vascularization and tumor cell proliferation. cEV also altered organs that were distant from the xenograft. These results suggest that lEVs in cancer patients are involved in both tumor growth and cancer progression.

Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2− γδ T cells, with equivalent representation of Vδ1+ and Vδ1− cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2− T cells can express the transcriptional program of exhausted αβ CD8+ T cells as well as canonical markers of terminal T-cell exhaustion including PD-1, TIGIT and TIM-3. Although Vδ2− γδ T cells have reduced IL-2 production, they retain expression of cytolytic effector molecules and co-stimulatory receptors such as 4-1BB. Exhausted Vδ2− γδ T cells are composed of three distinct populations that lack TCF7, are clonally expanded and express cytotoxic molecules and multiple Vδ2− T-cell receptors. Human tumor-derived Vδ2− γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2− T cells in pretreatment tumor biopsies was used to predict subsequent clinical responses to PD-1 blockade in patients with cancer. Thus, Vδ2− γδ T cells within the tumor microenvironment can contribute to antitumor efficacy.

High-content microscopy offers a scalable approach to screen against multiple targets in a single pass. Prior work has focused on methods to select “optimal” cellular readouts in microscopy screens. However, methods to select optimal cell line models have garnered much less attention. Here, we provide a roadmap for how to select the cell line or lines that are best suited to identify bioactive compounds and their mechanism of action (MOA). We test our approach on compounds targeting cancer-relevant pathways, ranking cell lines in two tasks: detecting compound activity (“phenoactivity”) and grouping compounds with similar MOA by similar phenotype (“phenosimilarity”). Evaluating six cell lines across 3214 well-annotated compounds, we show that optimal cell line selection depends on both the task of interest (e.g. detecting phenoactivity vs. inferring phenosimilarity) and distribution of MOAs within the compound library. Given a task of interest and set of compounds, we provide a systematic framework for choosing optimal cell line(s). Our framework can be used to reduce the number of cell lines required to identify hits within a compound library and help accelerate the pace of early drug discovery.

Advanced cutaneous squamous cell carcinoma (cSCC) can be a life-threatening disease for which effective and safe treatment in advanced stages is very limited. GP-2250 has been recently proven to have—in vitro and in vivo—antineoplastic effects on cancer cells. This study aims to investigate the potential anti-neoplastic effects of GP-2250 on the cSCC cell lines SCC13 and A431 through dose finding assessments, MTT cytotoxicity assays, cell migration assays, BrdU proliferation assays and FCM analysis. Our preliminary results have shown for the first time evidence for anti-neoplastic effects of GP-2250 on cSCC cells, enhancing cytotoxicity, attenuating cancer cell proliferation, inducing apoptosis and reducing tumour cell migration. Further investigations evaluating the modes of action of GP-2250 on cSCC cell lines are warranted in order to justify the use in vivo studies.

Adagrasib (MRTX849) is a KRASG12C inhibitor with favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration. As of September 1, 2022, a total of 853 patients with KRASG12C-mutated solid tumors, including patients with CNS metastases, had received adagrasib (monotherapy or in combination). Adagrasib-related treatment-related adverse events (TRAEs) are generally mild to moderate in severity, start early in treatment, resolve quickly with appropriate intervention, and result in a low rate of treatment discontinuation. Common TRAEs seen in clinical trials included gastrointestinal-related toxicities (diarrhea, nausea, and vomiting); hepatic toxicities (increased alanine aminotransferase/aspartate aminotransferase) and fatigue, which can be managed through dose modifications, dietary modifications, concomitant medications (such as anti-diarrheals and anti-emetics/anti-nauseants) and the monitoring of liver enzymes and electrolytes. To manage common TRAEs effectively, it is imperative that clinicians are informed, and patients are fully counseled on management recommendations at treatment initiation. In this review, we provide practical guidance on the management of adagrasib TRAEs and discuss some best practices for patient and caregiver counseling to facilitate optimal outcomes for patients. Safety and tolerability data from the phase II cohort of the KRYSTAL-1 study will be reviewed and presented with practical management recommendations based on our experience as clinical investigators.

Background: This study sought to investigate whether different physical function tests (objective measures of physical performance) may identify a low physical resilience in breast cancer survivors (BCS). Methods: This analytical cross-sectional study evaluated 146 BCS and 69 age-matched women without breast cancer history. The different times after the end of treatment were used as criteria for group division. Participants were divided into four groups: control (CT: n = 69–women without breast cancer history); 4 YAT: n = 41). Physical function was evaluated by 4 m walk test (4-MWT), five-times-sit-to-stand test (FTSST), timed up and go test (TUG), and short physical performance battery (SPPB). Age, menopausal status, smoking, number of medications, level of physical activity, body mass index, and muscle strength were used as confounding variables in ANCOVA. Results: All groups that underwent cancer treatment (

ObjectivesCurrent literature is lacking a comprehensive review of data on dietary interventions in blood pressure (BP) management in sub-Saharan African countries. We assessed the association of dietary and other lifestyle interventions with BP-lowering effects in populations within sub-Saharan Africa.MethodsWe performed a systematic review and random-effects meta-analysis to determine the impact of dietary and lifestyle interventions on SBP and DBP in sub-Saharan Africa. We searched the MEDLINE, EMBASE, and Web of Science databases. We included intervention studies that were randomized and nonrandomized conducted in Africans residing in sub-Saharan Africa investigating diet and other lifestyle, physical activity, weight loss, tobacco, and alcohol cessation modifications. We determined the effect of diet and other lifestyle interventions on SBP and DBP. We expressed effect size as weighted mean difference and 95% confidence interval (CI).Main results: We identified six studies with a total of 1412 individuals, 38% males, mean age of 52.8 years (SD = 11.5). The weighted mean difference of dietary and other lifestyle interventions on SBP and DBP was -7.33 mmHg, (95% CI: -9.90 to -4.76, P

Although shown to be effective in improving survival and quality of life in patients with cancer, some treatments are well-known causes of cardiotoxicity, such as anthracyclines, monoclonal antibodies against human epidermal growth factor receptor 2 (HER2) and radiotherapy. To prevent cardiovascular disease (CVD) in patients living with cancer, cardiologists and oncologists promoted the development of cardio-oncology, an interdisciplinary field which aims to further improving life expectancy in these patients. Cardio-oncology rehabilitation (CORE), through correction of risk factors, prescription of drug therapies and structured exercise programs, tries to improve symptoms, quality of life, cardiorespiratory fitness (CRF) and survival in patients with cancer. Different imaging modalities can be used to evaluate the real effectiveness of exercise training on cardiac function. Among these, the global longitudinal strain (GLS) has recently aroused interest, thanks to its high sensitivity and specificity for cardiac dysfunction detection due to advanced ultrasound programs. This review summarizes the evidence on the usefulness of GLS in patients with cancer undergoing cardiac rehabilitation programs.

ObjectiveThis study estimated the effect of hypothetical interventions of higher and lower frequency of breakfast and post-dinner snack consumption (breakfast consumption 0-4 vs. 5-7 times/week and post-dinner snack consumption 0-2 vs. 3-7 times/week) on changes in body weight and composition over 18 months after a successful 6-month standard behavioral weight-loss program.MethodsThe study analyzed data from the Innovative Approaches to Diet, Exercise and Activity(IDEA) study.ResultsIf all participants consumed a breakfast meal 5 to 7 times/week over 18 months, they would have regained 2.95 kg of body weight on average (95% CI: 2.01 to 3.96), which is 0.59 kg (95% CI: -0.86to -0.32) lower than if all participants consumed breakfast 0 to 4 times/week. If all participants consumed a post-dinner snack 0 to 2 times/week, they would have regained 2.86 kg of body weight on average (95% CI: 0.99 to 5.25), which is 0.83 kg (95% CI: -1.06 to -0.59) lower than if all consumed a post-dinner snack 3 to 7 times/week.ConclusionsRegular breakfast consumption and minimizing post-dinner snacking may modestly mitigate weight and body fat regain over 18 months after initial weight loss.

Long bone metastases are a disease of high social importance. The goals of surgical treatment are to relieve pain, maintain or restore joint function, and prevent or treat pathological fractures. "Oligometastases" is a disease with a limited number (3-5) of metastatic lesions in the same body district, where an aggressive treatment can be carried out with "curative" intent. This study aimed to evaluate patients with bone metastases surgically treated to determine how surgical treatment can influence prognosis and quality of life, comparing solitary metastasis, oligometastases, and multiple metastases.This is a retrospective analysis of 130 patients with long bone metastases surgically treated between October 2015 and August 2019: 40 patients had solitary metastasis; 38 had less than three metastases (oligometastases), and 52 had multiple metastases. Surgery was resection and reconstruction with a cemented prosthesis (95) or nailing (35).Overall survival was significantly better in patients with solitary metastasis or oligometastases than in those with multiple metastases (p0.0001). Patients treated with resection and prosthesis had significantly better survival than those treated with nailing (p0.0001). Implant complications requiring surgical revision occurred in 20 patients treated with prostheses, while no complications occurred in patients treated with nailing.Survival of cancer patients has improved in the last two decades, leading to an increase of diagnosed metastases. Patients with oligometastases have a survival similar to those with a single metastasis. Optimal implants survival curves should stay above the curves of patients survival.Since there are no differences in survival, patients with oligometastases should be treated as patients with a solitary lesion, with more aggressive surgery (wide resection and reconstruction with prosthesis). Intramedullary nailing is still indicated in metaphyseal or diaphyseal metastases in patients with advanced disease or poor prognosis when the life expectancy does not overcome the expected survival of the nail, avoiding the need for further surgery.

Funding Information: V. Känkänen and H.A. Santos acknowledge Bayer Oy (Finland) for financial support. H.A. Santos acknowledges also the Sigrid Jusélius Foundation and the UMCG Research Fund for financial support. Publisher Copyright: © 2022 The Authors The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation process and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribution (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to produce sorafenib-loaded PEG-b-PCL NPs and provides important insight into the effects of nanoprecipitation parameters and downstream processing on product quality.

Background: To research the influences of a Chinese traditional medicine (Citrus aurantium L.) on gastric cancer proliferation and mice gastrointestinal motility. Materials and Methods: The intesti...

SUMMARY OBJECTIVE: Glucose transporter-1 is a marker involved in energy transport in cancer cells. It has been shown to be a poor prognostic factor in many cancer types, including breast cancer. However, there is no satisfactory parameter predicting treatment in breast cancer patients receiving neoadjuvant therapy. This study investigated the effect of glucose transporter-1 in predicting the treatment response of patients receiving neoadjuvant therapy. METHODS: In this study, glucose transporter-1 immunohistochemistry was applied to tru-cut biopsy of patients who were diagnosed with breast cancer and received neoadjuvant therapy between 2010 and 2021. A built-in scoring system was used to evaluate both the pattern and intensity of glucose transporter-1 immunohistochemistry staining. The relationship between glucose transporter-1 immunohistochemistry staining and other clinicopathological parameters was examined. In addition, the relationship of glucose transporter-1 with response to treatment was investigated. RESULTS: A relationship was found between high glucose transporter-1 expression and other clinicopathological parameters (such as estrogen and progesterone receptor negativity, high Ki-67, triple-negative, and Her2 status). Cases with high glucose transporter-1 expression had either a complete or a partial pathologic response. The result was statistically significant. CONCLUSION: Glucose transporter-1 has the potential to be a biomarker that can be evaluated more objectively as an alternative to Ki-67 labeling index in evaluating the response to treatment in patients receiving neoadjuvant therapy.

An anal fissure is a painful tear of the sensitive anoderm, distally from the dentate line. It is a prevalent disorder and impairs quality of life dramatically. Typical or primary fissures are associated with constipation and mostly located at the posterior midline. About 1% of fissures are atypical in appearance and are generally secondary in nature. These secondary fissures should arouse attention and require further exploration for underlying conditions, such as Crohn's disease, malignancy, trauma or venereal infections. The aim of this manuscript is to provide a comprehensive review on the clinical aspects, evaluation and treatment of secondary anal fissures. (Acta gastroenterol. belg., 2023, 86, 58-67).

ContextPalliative care offers patient and family centered approaches that may mitigate risk of caregiver burden and poor mood.ObjectivesTo determine whether a palliative care intervention (CONNECT) improved burden, mood, and self-efficacy among caregivers of patients with advanced cancer.MethodsIn this cluster randomized trial, patients and their caregivers were recruited from 17 Oncology clinics in Pennsylvania. Participants attended nurse-led monthly visits, addressing patient symptoms, goals of care, and advance care planning. At baseline and three months, we measured caregiver burden using Zarit Burden Interview (ZBI-12; range 0-48), caregiver anxiety and depression using Hospital Anxiety and Depression Scales (HADS-A, range 0-21; HADS-D, range 0-21). We measured caregiver self-efficacy at three months using Caregiver Inventory (CGI; range 0-189).ResultsWe enrolled 441 caregivers and 381 completed three-month assessments. We found no significant differences in caregiver burden (adjusted mean difference -0.39; 95% CI -1.07-0.29, P=0.90), depression (adjusted mean difference -0.22, 95% CI -0.97-0.55, P=0.26), or anxiety (adjusted mean difference 0.09; 95% CI -1.25-1.43, P=0.58), between the intervention and standard care at three months. Caregiver self-efficacy was higher at three months in the intervention compared to standard care (adjusted mean difference 9.36; 95% CI 0.95-17.77, P=0.030).ConclusionCaregivers in CONNECT did not experience improved burden or mood, however, they reported higher self-efficacy compared to caregivers receiving standard care. This study highlights the need for strategies to optimize caregiver outcomes in palliative care interventions.

Background Cancer incidence is rising across the globe. The incidence and patterns of various cancers among Armed Forces Personnel and Veterans is not known. We did the analysis of registry data maintained at our hospital. Methods A retrospective analysis was performed of all patients registered at our hospital cancer registry between 01st January 2017 and 31st December 2019. Patients were registered with unique identification number. Baseline demographics and cancer subtype data were retrieved. Patients with histopathologically proven diagnosis and age ≥18 years were studied. Armed Forces Personnel (AFP) were defined as those who are in active service, and Veterans as those who had retired from service at the time of registration. Patients with Acute and Chronic Leukemias were excluded. Results New cases registered were 2023, 2856 and 3057 in year 2017, 2018, 2019 respectively. AFP, Veterans and dependents among them were 9.6%, 17.8%, and 72.6% respectively. Haryana, Uttar Pradesh and Rajasthan represented 55% of all cases with male to female ratio 1.14:1 and median age was 59 years. The median age among AFP was 39 years. Among AFP as well as veterans, Head and Neck cancer was the most common malignancy. Cancer incidence was significantly higher in adults >40 years as compared to Conclusion Seven percent rise per year of new cases in this cohort is alarming. Tobacco-related cancers were the most common. There is an unmet need to establish a prospective centralized Cancer Registry to better understand the risk factors, outcomes of treatment and strengthen the policy matters.