Cancer Cases Research Articles

Driver Mutations in Pancreatic Cancer and Opportunities for Targeted Therapy.

Pancreatic cancer is the sixth leading cause of cancer-related mortality globally. As the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC) represents up to 95% of all pancreatic cancer cases, accounting for more than 300,000 deaths annually. Due to the lack of early diagnoses and the high refractory response to the currently available treatments, PDAC has a very poor prognosis, with a 5-year overall survival rate of less than 10%. Targeted therapy and immunotherapy are highly effective and have been used for the treatment of many types of cancer; however, they offer limited benefits in pancreatic cancer patients due to tumor-intrinsic and extrinsic factors that culminate in drug resistance. The identification of key factors responsible for PDAC growth and resistance to different treatments is highly valuable in developing new effective therapeutic strategies. In this review, we discuss some molecules which promote PDAC initiation and progression, and their potential as targets for PDAC treatment. We also evaluate the challenges associated with patient outcomes in clinical trials and implications for future research.

External validation of the RIETE and SOME scores for occult cancer in patients with venous thromboembolism: a multicentre cohort study

External validation of the RIETE and SOME scores for occult cancer in patients with venous thromboembolism: a multicentre cohort study

Factors influencing presentation delay among cancer patients: a cross-sectional study in Malaysia

BackgroundCancer represents a significant global public health challenge, with escalating incidence rates straining healthcare systems. Malaysia, like many nations, has witnessed a rise in cancer cases, particularly among the younger population. This study aligns with Malaysia’s National Strategic Plan for Cancer Control Programme 2021–2025, emphasizing primary prevention and early detection to address cancer’s impact. Therefore, we aim to describe the timeliness of cancer care for symptom presentation, socio-demographic, patient, as well as organizational-related factors among patients in Malaysia diagnosed with breast, colorectal, nasopharyngeal, and cervical cancer.MethodsThis cross-sectional study enrolled adult cancer patients diagnosed with breast, cervical, colorectal, or nasopharyngeal cancer from 2015 to 2020 in seven public hospitals/oncology centres across Malaysia. Data were collected through patient-administered surveys and medical records. Presentation delay, defined as the duration between symptom onset and the patient's first visit to a healthcare professional exceeding 30 days, was the primary outcome. Statistical analysis included descriptive statistics and chi-square tests.ResultsThe study included 476 cancer patients, with breast cancer (41.6%), colorectal cancer (26.9%), nasopharyngeal cancer (22.1%), and cervical cancer (9.5%). Over half (54.2%) experienced presentation delays with a median interval of 60 days. Higher proportions of presentation delay were observed among nasopharyngeal cancer patients, employed patients with lower socioeconomic statuses, and those without family history of cancer. Most patients self-discovered their first cancer symptoms (80%), while only one-third took immediate action for medical check-ups. Emotional and organizational factors, such as long waiting times during doctor's visits (47%), were potential barriers to seeking cancer care.ConclusionThis study highlights the significant problem of presentation delay among cancer patients in Malaysia. The delay is influenced by various factors encompassing sociodemographic characteristics, health-seeking behaviours, and healthcare system-related issues. A comprehensive approach addressing both individual barriers and institutional obstacles is imperative to mitigate this presentation delay and improve cancer outcomes.

Investigating the efficacy of tissue factor pathway inhibitor‑2 as a promising prognostic marker for ovarian cancer.

Tissue factor pathway inhibitor-2 (TFPI2) is a tumor marker for diagnosing ovarian cancer and ovarian clear cell carcinoma (OCCC); however, its effectiveness as a prognostic marker remains unclear. The present study aimed to investigate the utility of TFPI2 as a prognostic marker for ovarian cancer. A total of 256 cases of ovarian cancer was collected at Nara Medical University (Kashihara, Japan) from January 2008 to January 2022. The majority of cases were serous carcinoma (109, 42.6%), followed by OCCC (66, 25.8%), mucinous carcinoma (40, 15.6%), endometrial carcinoma (15, 5.9%), and other (26, 10.2%). The median preoperative serum TFPI2 for ovarian cancer was 219.0 (82.5-5,824.2) pg/ml. Overall survival (OS) of patients with non-OCCC and OCCC was calculated using the cut-off value determined obtained through receiver operating characteristic curve analysis. Cut-off values of TFPI2 for OS were 201 for non-OCCC and 255 pg/ml for OCCC. In univariate analysis, OS was significantly elevated in patients with non-OCCC and OCCC who had TFPI2 levels ≥201 pg/ml (P<0.001) and ≥255 pg/ml (P=0.036), respectively. Progression-free survival (PFS) was significantly elevated in patients with non-OCCC and OCCC who had TFPI2 levels ≥201 and ≥255 pg/ml (both P<0.001), respectively. Multivariate analysis revealed that OS was significantly higher in patients with non-OCCC who had TFPI2 levels ≥201 pg/ml (P=0.021), while PFS was significantly higher in patients with OCCC who had TFPI2 levels ≥255 pg/ml (P=0.020). These findings suggest that TFPI2 is a potential prognostic marker for ovarian carcinoma.

Spatial and temporal analysis of thyroid cancer incidence in Guilan Province, Northern Iran, 2009–2018

BackgroundThyroid cancer is one of the most common malignancies of the endocrine system, the fifth most common malignancy in women worldwide, and the second most common cancer in women over 50 in 2019. It is the sixth most common cancer in both sexes and the third most common cancer in women in Guilan province. This study was conducted to describe the geographic variation and investigate any changes in the trend of the thyroid cancer incidence rate. MethodsThis study was conducted on the data of the Guilan University of Medical Sciences cancer registration system. The crude and age-standardized incidence rate was calculated per 100,000 person-years. Joinpoint regression analysis evaluated the time trends and annual percent changes (APC). The incidence rate was estimated separately for each city and high-risk areas were shown on the province map using GIS software. Results1742 cases of thyroid cancer (83.7 % in women and 16.3 % in men) were registered in Guilan province from 2009 to 18. The incidence of thyroid cancer was 5.1-fold higher in women than men. The results of the joinpoint regression analysis showed that the age-standardized incidence rate of thyroid cancer in both sexes has increased significantly over ten years (APC: 26.4; 95 %CI: 22.5–30.4), (P-value < 0.001). In our study, Astaneh-ye Ashrafiyeh, Lahijan, and Langarud cities were identified as high-risk areas of the province for both sexes. ConclusionThe trend of incidence of thyroid cancer in Guilan province is increasing. Also, a wide geographical variation was found in the incidence of thyroid cancer.

The National Cancer Database Conforms to the Standardized Framework for Registry and Data Quality.

Standardization of procedures for data abstraction by cancer registries is fundamental for cancer surveillance, clinical and policy decision-making, hospital benchmarking, and research efforts. The objective of the current study was to evaluate adherence to the four components (completeness, comparability, timeliness, and validity) defined by Bray and Parkin that determine registries' ability to carry out these activities to the hospital-based National Cancer Database (NCDB). Tbis study used data from U.S. Cancer Statistics, the official federal cancer statistics and joint effort between the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI), which includes data from National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology, and End Results (SEER) to evaluate NCDB completeness between 2016 and 2020. The study evaluated comparability of case identification and coding procedures. It used Commission on Cancer (CoC) standards from 2022 to assess timeliness and validity. Completeness was demonstrated with a total of 6,828,507 cases identified within the NCDB, representing 73.7% of all cancer cases nationwide. Comparability was followed using standardized and international guidelines on coding and classification procedures. For timeliness, hospital compliance with timely data submission was 92.7%. Validity criteria for re-abstracting, recording, and reliability procedures across hospitals demonstrated 94.2% compliance. Additionally, data validity was shown by a 99.1% compliance with histologic verification standards, a 93.6% assessment of pathologic synoptic reporting, and a 99.1% internal consistency of staff credentials. The NCDB is characterized by a high level of case completeness and comparability with uniform standards for data collection, and by hospitals with high compliance, timely data submission, and high rates of compliance with validity standards for registry and data quality evaluation.

The Impact of a 6-Week Nordic Walking Training Cycle and a 14-Hour Intermittent Fasting on Disease Activity Markers and Serum Levels of Wnt Pathway-Associated Proteins in Patients with Multiple Myeloma.

Background: Multiple myeloma (MM) accounts for about 10-15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Materials and methods: Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60 min workouts 3 times a week was conducted. Body mass and composition as well as the levels of vitamin D, calcium and phosphorus, beta2-microglobulin, and albumin were examined before and after the completion of the training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN), and Tartrate-resistant acid phosphatase 5b (TRACP 5b). Results: There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumins was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p = 0.001 and p = 0.022, respectively). The change in the concentration of this vitamin negatively correlated with the concentration of TRACP 5b (r = -0.413, p = 0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p = 0.026, time vs. group: p = 0.033) and TRACP 5b (time: p < 0.001, time vs. group p < 0.001) was indicated. Conclusions: The obtained results allow one to indicate the training with the poles as a safe and beneficial form of physical activity that should be recommended to patients suffering from MM. However, the results obtained in the present study are not sufficient to show the beneficial effect of IF applied without trainings.

Predictors of Metastasis in 68GA-Prostate Specific Membrane Antigen Pet-CT in the Primary Staging of Prostate Cancer.

Background: The objective of this study was to investigate factors influencing Gallium 68 Prostate Specific Membrane Antigen Positron Emission Tomography (Ga68 PSMA PET-CT) uptake for primary staging in prostate cancer. Methods: Retrospective analysis was conducted on 499 non-metastatic and 243 de novo metastatic prostate cancer cases undergoing Ga68 PSMA PET-CT. Demographic, clinical, and imaging data were collected and analyzed. Multivariate logistic regression determined independent risk factors for metastasis detection on Ga68 PSMA PET-CT. Results: Metastatic cases showed higher levels of total PSA, PSA density (dPSA) and biopsy ISUP grade group compared to non-metastatic cases. Multivariate analysis identified cT2 stage and dPSA as independent predictors of metastasis detection on Ga68 PSMA PET-CT. Conclusions: Ga68 PSMA PET-CT plays a crucial role in prostate cancer staging, with identified factors such as clinical T stage and dPSA significantly impacting its diagnostic accuracy. These findings underscore the importance of Ga68 PSMA PET-CT in refining clinical staging and guiding treatment decisions for prostate cancer patients.

Association between postoperative radiotherapy for young-onset non-small cell lung cancer and risk of second primary malignancies ----Comparative study.

The most common form of therapy for non-small cell lung cancer (NSCLC) in early stage is surgery-based combination therapy, including radiotherapy and immunotherapy. However, postoperative radiotherapy (PORT) of cancer is correlated with increasing risk of second primary malignancy (SPM), especially young-onset cancer cases. We aimed to quantify the risks of SPM associated with PORT treatment for young‑onset NSCLC in early stage. We screened for SPM that developed over 5 years since the diagnosis of NSCLC. Using the data from the Surveillance, Epidemiology and End Results database, PORT-correlated risks were estimated with multivariate Logistic regression analysis. Moreover, Fine-Gray's competing risk regression analysis was used to calculate the cumulative incidence of SPMs. Among the 30308 young-onset NSCLC patients in early stage undergoing surgery, a total of 3728 patients have received PORT. Logistic regression analyses showed that PORT showed substantial correlation with elevated risks of second solid malignancies (RR = 1.31; 95% CI: 1.17-1.46), lung cancer (RR=1.23; 95% CI: 1.07-1.42), breast cancer (RR=1.74; 95% CI: 1.16-2.74) and colon and rectum cancers (RR=1.37; 95% CI: 1.07-2.06) as well as a negligible risk of second hematologic malignancies (RR = 1.15; 95% CI: 0.82-1.67). The cumulative incidence of SPMs revealed similar findings. Higher RR was obtained in NSCLC patients aged 60 to 69 years (RR = 1.33), in white race (RR = 1.36), diagnosed in 1975-2000 (RR = 1.23) and 2001-2015 (RR = 1.40), or diagnosed with lung adenocarcinoma (RR = 1.55). PORT for young-onset NSCLC in early stage was correlated with elevated risks of SPMs (lung cancer, breast cancer as well as colon and rectum cancers), supporting the need for long-term surveillance of these patients.

The current infection with Helicobacter pylori and association with upper gastrointestinal lesions and risk of upper gastrointestinal cancer: Insights from multicenter population-based cohort study.

The relationship between Helicobacter pylori (H. pylori) infection and upper gastrointestinal (UGI) cancers is complex. This multicenter, population-based cohort study conducted in seven areas in China aimed to assess the correlation between current H. pylori infection and the severity of UGI lesions, as well as its association with the risk of gastric cancer (GC) and esophageal cancer (EC). From 2015 to 2017, 27,085 participants (aged 40-69) completed a standardized questionnaire, and underwent a 13C-urea breath test. Then a subset underwent UGI endoscopy to assess the UGI lesion detection rates. All individuals were followed up until December 2021 to calculate the hazard ratios (HRs) for UGI cancers. H. pylori infection prevalence was 45.9%, and among endoscopy participants, 22.2% had gastric lesions, 19.2% had esophageal lesions. Higher detection rates of gastric lesions were noted in the H. pylori-positive population across all lesion severity levels. Over a median follow-up of 6.3 years, 104 EC and 179 GC cases were observed, including 103 non-cardia gastric cancer (NCGC) cases and 76 cardia gastric cancer (CGC) cases. H. pylori-infected individuals exhibited a 1.78-fold increased risk of GC (HR 1.78, 95% confidence interval [CI] 1.32-2.40) but no significant increase in EC risk (HR 1.07, 95% CI 0.73-1.57). Notably, there was a higher risk for both NCGC and CGC in H. pylori-infected individuals. This population-based cohort study provides valuable evidence supporting the association between current H. pylori infection and the risk of both NCGC and CGC. These findings contribute to the empirical basis for risk stratification and recommendations for UGI cancer screening.

Association between BMI and oncologic outcomes in epithelial ovarian cancer: a predictors-matched case-control study.

We aimed to study the association between obesity and survival in ovarian cancer (OC) patients, accounting for confounders as disease stage, histology, and comorbidities. Retrospective matched case-control study of consecutive patients, with epithelial OC. Obese (body mass index [BMI] ≥ 35 kg m-2) patients were matched in a 1:4 ratio with patients having lower BMIs (BMI < 35 kg m-2) based on disease stage, cytoreduction state, tumor histology and ASA score. We compared the 3-year and total recurrence-free survival and overall survival through Kaplan-Meier survival curves and Cox proportional hazards. Overall, 153 consecutive patients were included, of whom 32 (20.9%) had a BMI ≥ 35. and 121 a BMI < 35. The median follow-up time was 39 months (interquartile range 18-67). Both study groups were similar in multiple prognostic factors, including American Society of Anesthesiologists physical status, completion of cytoreduction, histology and stage of disease (p = 0.981, p = 0.992, p = 0.740 and p = 0.984, respectively). Ninety-five (62.1%) patients underwent robotic surgery and conversion rate from robotic to laparotomy was similar in both groups 2 (6.3%) in obese group vs. 6 (5.0%) in lower BMI patients, p = 0.673. During the follow-up time, the rate of recurrence was similar in both groups; 21 (65.6%) in obese group vs. 68 (57.1%), p = 0.387 and the rate of death events was similar; 16 (50.0%) in obese group vs. 49 (40.5%), p = 0.333). The 3-year OS was higher in the obese group (log rank p = 0.042) but the 3-year RFS was similar in both groups (log rank p = 0.556). Median total OS was similar in both groups 62 months (95% confidence interval 25-98 months) in obese vs. 67 months (95% confidence interval 15-118) in the lower BMI group, log rank p = 0.822. Median RFS was similar in both groups; 61 months (95% confidence interval 47-74) in obese, vs. 54 (95% confidence interval 43-64), log rank p = 0.842. In Cox regression analysis for OS, including obesity, age, laparotomy and neoadjuvant treatment - only neoadjuvant treatment was independently associated with longer OS: odds ratio 1.82 (95% confidence interval 1.09-3.05) and longer RFS: odds ratio 2.16 (95% confidence interval 1.37-3.41). In the present study on consecutive cases of ovarian cancer, obesity did not seem to be associated with outcome, except for an apparent improved 3-year survival that faded away thereafter.

A Prospective Study to Evaluate the Prevalence of Microsatellite Instability in Endometrial Carcinoma by using Immunohistochemistry for Mismatch Repair Proteins as a Surrogate Marker

Abstract Aim Use of immunohistochemistry for mismatch repair (MMR) proteins to identify the prevalence of microsatellite instability (MSI) in cases of endometrial carcinoma and its subsequent correlation with various histopathological parameters. Materials and Methods The expression of MMR proteins, viz PMS2, MLH1, MSH2, and MSH6, were assessed in 114 endometrial cancer cases by immunohistochemistry using Dako EnVision FLEX system, on paraffin blocks of tumor tissue fixed in 10% formalin. Results We studied 114 endometrial cases for MMR protein expression, of which the majority were of endometrioid histologic subtype (n = 93, 81.6%), whereas the remainder comprised serous carcinoma (n = 12, 10.5%), clear cell carcinoma (n = 1, 0.9%), carcinosarcoma (n = 5, 4.4%), and dedifferentiated uterine carcinoma (n = 3, 2.6%). Twenty-one (18%) of these cases were found to be deficient for MMR proteins, of which 20 were of endometrioid histologic subtype and only 1 was dedifferentiated uterine carcinoma. Loss of MMR protein expression occurred in pairs of either PMS2 and MLH1 or MSH2 and MSH6. Conclusion MSI is one of the major molecular pathways contributing to tumorigenesis in endometrial carcinomas. Immunohistochemistry for MMR proteins is a highly sensitive and cost-effective alternative for molecular testing for MSI. It is also a great tool for screening patients for Lynch syndrome. Immunohistochemical testing for MMR should be offered to all patients of endometrial cancers.

Using RNN Artificial Neural Network to Predict the Occurrence of Gastric Cancer in the Future of the World

Gastric cancer is an important health problem and is the fourth most common cancer and the second leading cause of cancer-related deaths worldwide. The incidence of stomach cancer is increasing and it can be dealt with using new methods in prediction and diagnosis. Our goal is to implement an artificial neural network to predict new cancer cases. Gastric cancer is anatomically divided into true gastric adenocarcinomas (non-cardiac gastric cancers) and gastric-esophageal- connective cancer (adenocardia (cardiac) gastric cancers). We use MATLAB R2018 software (MathWorks) to implement an artificial neural network. We used. The data were repeatedly and randomly divided into training (70%) and validation (30%) subsets. Our predictions emphasize the need for detailed studies on the risk factors associated with gastric cell carcinoma to reduce the incidence and has also provided an accuracy of about 99.998%.

A case of sporadic metastatic medullary cancer with distant metastases and negative RET mutation

A case of sporadic metastatic medullary cancer with distant metastases and negative RET mutation

Correlation of gasdermin B staining patterns with prognosis, progression, and immune response in colorectal cancer

BackgroundPyroptosis is a type of programmed cell death mediated by the gasdermin family. Gasdermin B (GSDMB), as a member of gasdermin family, can promote the occurrence of cell pyroptosis. However, the correlations of the GSDMB expression in colorectal cancer with clinicopathological predictors, immune microenvironment, and prognosis are unclear.MethodsSpecimens from 267 colorectal cancer cases were analyzed by immunohistochemistry to determine GSDMB expression, CD3+, CD4+, and CD8+ T lymphocytes, CD20+ B lymphocytes, CD68+ macrophages, and S100A8+ immune cells. GSDMB expression in cancer cells was scored in the membrane, cytoplasm, and nucleus respectively. GSDMB+ immune cell density was calculated. Univariate and multivariate survival analyses were performed. The association of GSDMB expression with other clinicopathological variables and immune cells were also analyzed. Double immunofluorescence was used to identify the nature of GSDMB+ immune cells. Cytotoxicity assays and sensitivity assays were performed to detect the sensitivity of cells to 5-fluorouracil.ResultsMultivariate survival analysis showed that cytoplasmic GSDMB expression was an independent favorable prognostic indicator. Patients with positive cytoplasmic or nuclear GSDMB expression would benefit from 5-fluorouracil based chemotherapy. The assays in vitro showed that high GSDMB expression enhanced the sensitivity of colorectal cancer cells to 5-fluorouracil. Patients with positive membranous or nuclear GSDMB expression had more abundant S100A8+ immune cells in the tumor invasive front. Positive nuclear GSDMB expression indicated more CD68+ macrophages in the tumor microenvironment. Moreover, GSDMB+ immune cell density in the stroma was associated with a higher neutrophil percentage but a lower lymphocyte counts and monocyte percentage in peripheral blood. Furthermore, the results of double immunofluorescence showed that GSDMB co-expressed with CD68 or S100A8 in stroma cells.ConclusionThe GSDMB staining patterns are linked to its role in cancer progression, the immune microenvironment, systemic inflammatory response, chemotherapeutic efficacy, and prognosis. Colorectal cancer cells with high GSDMB expression are more sensitive to 5-fluorouracil. However, GSDMB expression in immune cells has different effects on cancer progression from that in cancer cells.

Efficacy of the minimal-invasive vacuum-assisted biopsy under direct visualization with ultrasound for impalpable breast lesions in Taiwanese female: A retrospective case-control study

Abstract Background Although surgical excisional biopsy provides robust diagnostic results, the ultrasound-assisted vacuum-assisted biopsy (VABB) offers an alternative for Asian candidates with dense breasts and lesions which cannot be approached by stereotactic biopsy. The study aims to investigate the efficacy of the ultrasound-assisted VABB for impalpable mammographic-detected lesions. Methods A retrospective case-control study is conducted in a group of Taiwanese female patients who have impalpable breast lesions such as microcalcifications at screening mammography that are limited to BI-RADS category 4. Specifically, the lesions are categorized into three groups: 4a, 4b, 4c, and the histology from B2 through B5. The cases underwent ultrasound-assisted VABB and the controls had lumpectomies. The diagnostic accuracy, rate of discordance, excited tumor size, and the proportion of cancer cases is evaluated and compared using Fisher’s Exact test, Cohen’s kappa test, Chi-Square test, and the use of IBM SPSS statistical programs. Results The histology of the majorities of the collected specimen are B2 benign fibrocystic changes (60-70%). In cases of patients who are diagnosed with breast cancer, most are ductal carcinoma in situ and early-stage diseases. The cancer risks for lesions categorized under BI-RADS 4a, 4b, 4c respectively are consistent with clinical practice. Meanwhile, the diagnostic accuracy of VABB is similar to lumpectomy, as the histologic discordance rate did not differ significantly. Conclusions Ultrasound-assisted VABB does offer an option for patients who are not candidates for stereotactic biopsy, as it has shown to have non-inferior diagnostic values and cosmetic benefits when compared to surgical excision. The use of sonography monitors the biopsy process and guides the needle insertion thus is capable of obtaining samples from multiple directions, without risking the pectoralis muscles underneath. However, VABB may be intended for biopsies in lower-risk findings such as BI-RADS category 4a because doubts persist as complete excisional rates are operator-dependent.

Appendectomy and Long-term Colorectal Cancer Incidence, Overall and by Tumor Fusobacterium nucleatum Status.

To test hypotheses that appendectomy history might lower long-term colorectal cancer risk and that the risk reduction might be strong for tumors enriched with Fusobacterium nucleatum, bacterial species implicated in colorectal carcinogenesis. The absence of the appendix, an immune system organ and a possible reservoir of certain pathogenic microbes, may affect the intestinal microbiome, thereby altering long-term colorectal cancer risk. Utilizing databases of prospective cohort studies, namely the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of appendectomy history with colorectal cancer incidence overall and subclassified by the amount of tumor tissue Fusobacterium nucleatum​​ (Fusobacterium animalis). We used an inverse probability weighted multivariable-adjusted duplication-method Cox proportional hazards regression model. During the follow-up of 139,406 participants (2,894,060 person-years), we documented 2811 incident colorectal cancer cases, of which 1065 cases provided tissue F. nucleatum analysis data. The multivariable-adjusted hazard ratio of appendectomy for overall colorectal cancer incidence was 0.92 (95% CI, 0.84-1.01). Appendectomy was associated with lower F. nucleatum-positive cancer incidence (multivariable-adjusted hazard ratio, 0.53; 95% CI, 0.33-0.85; P=0.0079), but not F. nucleatum-negative cancer incidence (multivariable-adjusted hazard ratio, 0.98; 95% CI, 0.83-1.14), suggesting a differential association by F. nucleatum status (Pheterogeneity=0.015). This differential association appeared to persist in various participant/patient strata including tumor location and microsatellite instability status. Appendectomy likely lowers the future long-term incidence of F. nucleatum-positive (but not F. nucleatum-negative) colorectal cancer. Our findings do not support the existing hypothesis that appendectomy may increase colorectal cancer risk.

Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California

BackgroundMaternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer. MethodsThe present study included 15,744 cancer cases (aged 0–19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998–2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned “ever/never” and “high/low exposed/unexposed” exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy. Results1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the “ever exposed” group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74). ConclusionsOverall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

Association between fish and shellfish consumption, n-3polyunsaturated fatty acids, and gastric cancer risk: the Japan Public Health Center-based Prospective Study.

Fish and shellfish consumption is suggested to be a cancer-protective factor. However, studies investigating this association for gastric cancer, especially considering Helicobacter pylori (H. pylori) and atrophic gastritis (AG), are limited. We investigated gastric cancer risk associated with fish, shellfish, and n-3 polyunsaturated fatty acids (n-3 PUFAs)consumption among Japanese adults. 90,504 subjects enrolled in the Japan Public Health Center-based Prospective Study(JPHC Study) were followed until December 2013. Dietary intake data were collected using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) werecalculated for gastric cancer risk associated with fish and shellfishconsumption and marine n-3 PUFAs (sum of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)) using Cox proportional hazards models. Among those with avaliable data, we conducted a subgroup analysis takingH. pylori infectionand AGstatusinto consideration. There were 2,701 gastric cancer cases during an average of 15years of follow-up. We observed an increased gastric cancer risk for salted fish consumption for men [HR for fifth quintile versus first quintile 1.43 (95% CI 1.18-1.75)] and for women [HR 1.33 (95% CI 1.00-1.77)]. We observed a weak risk reduction trend for women as the intake ofmarine n-3 PUFAs increased (p-trend:0.07). When we included H. pylori infection and atrophic gastritis status in the analysis, the associations diminished. Our results suggest that salted fish increases gastric cancer risk for men and women, while marine n-3 PUFAs marginally decreases this risk among women in Japan.

A multiobjective beam angle optimization framework for intensity-modulated radiation therapy

Radiation therapy treatment planning is inherently a multiobjective problem, aiming to obtain the best tradeoffs between irradiating the tumor with the prescribed dose and sparing as much as possible the surrounding healthy organs. Many different multiobjective approaches have been proposed for the optimization of radiation intensities for fixed beam irradiation directions. However, multiobjective beam angle optimization is seldom considered. The purpose of this paper is to introduce a new multiobjective optimization framework that explicitly and simultaneously considers the optimization of intensities and also beam directions. Whilst multiobjective optimization of radiation intensities considering a fixed set of beam directions gives rise to a single Pareto front, beam angle optimization gives rise to the appearance of multiple Pareto fronts, each one associated with a given beam angle set. Our framework proposes a beam angle set choice based on the evaluation of non-dominated solutions belonging to different Pareto fronts, using a tree-based approach and a performance indicator to assess the quality of each Pareto front. The proposed approach, illustrated by head-and-neck cancer cases, allows for more flexibility in the calculation of solutions and a better understanding of the existing compromises between different objectives.