bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic testing of Japanese patients with serrated polyposis syndrome: A multicentric study.
Authors: Takao Akinari , Yamaguchi Tatsuro , Eguchi Hidetaka , Okazaki Yasushi , Ishikawa Hideki , Akagi Kiwamu , Ishida Hideyuki 
Published: January 2024

75 Background: Serrated polyposis syndrome (SPS) is a rare condition associated with an increased risk of colorectal cancer. Previous studies have identified germline truncating variants of the RNF43; however, patients harboring these variants comprise a small part of those with SPS, in most of whom the causative gene remains unknown. To date, no study has described the genetic features of Japanese patients with SPS. The present study aimed to identify candidate causative genes of SPS in Japanese patients. Methods: Captures for equal to or more than 55 gene regions were performed using Agilent HaloPlex or Ion AmpliSeq technologies in SPS patients enrolled in The Study Group for Establishment of Diagnosis of Hereditary Gastrointestinal Tract Cancer Syndromes Based on a Next-Generation Sequencing Technology (SGHGCS). Whole exome sequencing of tumor tissue was performed whenever a candidate gene was identified. Results: Eleven patients (four males, seven females) were enrolled. Of these, nine had a history of colorectal cancer; four had a family history of colorectal cancer; and two had a family history of polyposis. Genetic testing identified two variants of VUS, POLD1 c.670C>T (p.R224C) and BRCA2 c.4169T>G (p.L1390W). Additionally, a nonsense variant, BUB1:c.1543G>T p.Gly515Ter was deemed likely to be pathogenic. The patient with the BUB1 variant was 47-year-old female with transverse colon cancer with more than 50 serrated polyps. She was a non-smoker. The variants detected in the transverse colon cancer did not include the canonical variants in common colorectal cancer, such as APC, KRAS or TP53 and were mostly transition substitutions (C>T). Conclusions: BUB1 was identified as a novel candidate causative gene of SPS in a patient with SPS with no smoking habit. These findings will hopefully contribute to our understanding of the genetic basis of SPS.
One of these is not like the others: A descriptive study of the attenuated phenotype of PMS2.
Authors: Esplin Edward D. , Heald Brandie , Nielsen Sarah M. , Ellsworth Rachel , Russell Emily M. , Pineda Alvarez Daniel Esteban 
Published: January 2024

76 Background: Data from Lynch syndrome (LS) registries reveal that patients (pts) with PMS2 pathogenic germline variants (PGVs) have the lowest cancer risk. This retrospective study of pts undergoing germline genetic testing (GGT) for any indication compared the phenotypes of PMS2 carriers to other LS pts. We hypothesized that PMS2 pts were more likely to have no cancer or non–LS associated cancers than other LS pts. Methods: All Pts with a single PGV in any LS gene were identified from a commercial laboratory database. Demographics and personal and family cancer history data were clinician-reported on the test requisition form. Data from PMS2 pts were compared to MSH6 and MLH1/MSH2/EPCAM pts using descriptive statistics, unpaired two-samples t tests, Chi-square tests, and multivariate logistic regression analyses that also included patients with no PGVs, with p<0.05 defining significance. Results: 17,711 pts met inclusion criteria (5,189 PMS2, 5,182 MSH6, and 7,340 MLH1/MSH2/EPCAM). PMS2 pts were significantly older at testing (mean 55.1±16.0y) than MLH1/MSH2/EPCAM (48.7±15.7y) and had significantly less family cancer history (84.9%) than both MSH6 (86.8%) and MLH1/MSH2/EPCAM (86.6%) pts. PMS2 pts had lower odds of any colorectal and uterine cancers than the MSH6 and MLH1/MSH2/EPCAM cohorts (Table). All LS-related PGVs were significantly associated with lower odds of breast, pancreatic, and prostate cancer. Conclusions: Pts with PMS2 PGVs were older at the time of testing and had lower odds of any and LS-related cancers than other LS pts. These data are consistent with prior registry studies and can aid in counseling and management of PMS2 pts. [Table: see text]
Insulin resistance and impaired insulin secretion and gastrointestinal cancer risk in Korean adults: Preliminary results from Korean Genome and Epidemiology study.
Authors: Jo Hyemin , Shin Cheol Min , Ahn Soyeon , Ohn Jung Hun , Ji Eunjeong , Choi Yonghoon , Jun Yu Kyung , Yoon Hyuk , Park Young Soo , Kim Nayoung , Lee Dong Ho 
Published: January 2024

761 Background: To date, few studies conducted on the effect of insulin resistance or insulin secretory function on cancer risk in non-diabetic population. This study evaluated whether insulin resistance and/or insulin secretory function affect gastrointestinal cancer risk in the Korean population. Methods: We analyzed data from Korean Genome and Epidemiology Study, Korea Association Resource dataset. It consists of 10,030 participants aged 40-69y observed from 2001 to 2018. The risk of all cancers, and gastrointestinal cancers were assessed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Homeostasis Model Assessment of Beta-cell function (HOMA-β) were used as indicators of insulin resistance and insulin secretory function. Results: In the final dataset, 8,649 individuals without previous history of any cancers were included. During an average follow-up of 15 years, 415 subjects (4.8%) developed cancers. Compared to the low HOMA-IR/high HOMA-β group (reference), diabetic patients had the highest risk of overall cancers, followed by high HOMA-IR/low HOMA-β group (Adjusted hazard ratio[95% confidence interval]: 1.74 [1.11 - 2.75] and 1.40 [0.96 – 2.06], respectively) Among gastrointestinal cancers, the risk of gastric cancer was higher in the low HOMA-IR/low HOMA-β and high HOMA-IR/high HOMA-β groups (1.92 [1.06 - 3.47] and 2.27 [1.26 - 4.06], respectively) When further analyzed by HOMA-β stratified by quartiles, the lowest quartile (Q1) showed an increased risk of gastric cancer compared to the highest-quartile (Q4; 1.84 [0.98 – 3.46], p = 0.06) In contrast, no significant results were observed regarding the colorectal cancer risk, when analyzed based on HOMA-IR and HOMA-β. However, when further analyzed by HOMA-IR stratified by quartiles, the highest quartile (Q4) exhibited a significantly elevated colorectal cancer risk compared to the lowest quartile (Q1; 2.14 [1.11 - 4.11], P for trend = 0.04). Conclusions: Insulin resistance and impaired insulin secretion function may increase the risk of cancer, but the underlying mechanisms may differ by cancer type.
Characterizing the rare abdominal neoplasms of peritoneum, retroperitoneum, and overlapping sites of peritoneum and retroperitoneum: A review of NCDB database.
Authors: Jafry Baqir , Kazmi Syed Mohammad Ali 
Published: January 2024

764 Background: The tumor characteristics of the rare abdominal tumors including peritoneum (PT), retroperitoneum (RT) and overlapping sites of peritoneum and retroperitoneum (OT) remain unexplored. Methods: From the National Cancer Database, we identified all patients who were diagnosed with tumors in PT, RT or OT from 2004 to 2016. We evaluated the incidence of each tumor across time and compared population characteristics of each of these tumors. Results: We identified a total of 47300 patients - 22090 had PT, 11837 had RT and 13373 had OT. The mean age of PT was 66.9 while that of RT and OT was 61.2 and 68.1 respectively. All three cancers had a higher percentage of females compared to males (93.8% for peritoneum; 50.4% for retroperitoneum; 50.6% for overlapping sites), whites (88.8% for PT; 83.6% for RT; 81.5% for OT), insured patients (97.8% for PT; 96.2% for RT; 96% for OT) and patients without any existing comorbidities (75.9% for PT; 77.5% for RT; 67.7% for OT). The most common histology was adenocarcinoma in OT, leiomyosarcoma in RT, serous epithelial carcinoma among the PT population. These neoplasms had higher proportions of grade 3 tumors (58% for PT; 32.2% for RT; 50.9% for OT), patients with income > $63,333 (38.6% for PT; 38.1% for RT; 36.6% for OT), and patients residing in an area where 6.3%-10.8% did not graduate from high school (29.8% for PT; 29.7% for RT; 23.8% for OT). From 2004 to 2016, there was a significant increase in the number of tumors of overlapping sites (566 in 2004 to 1848 in 2016) while the number of PT (1580 in 2004 to 1586 in 2016) and RT (726 in 2004 to 980 in 2016) did not change significantly. Conclusions: Among the rare abdominal neoplasms, the number of OT have increased from 2004-2016 while that of PT and RT tumors have remained stable. The histology patterns are consistent with known cancers that involve these regions.
Impact of revising colorectal cancer screening guidelines on health care resources in Canada.
Authors: Chia Brendan , Ruan Yibing , Brown Carl J. , Brenner Darren R , Loree Jonathan M. 
Published: January 2024

78 Background: The rising incidence of early-onset colorectal cancer (CRC) has prompted U.S. organizations to lower the recommended CRC screening age for average risk adults from 50 to 45 years old, while Canadian programs remain unchanged. Canadian guidelines also differ from the U.S. in preferentially screening with a fecal immunochemical test (FIT) and recommending against colonoscopies as a screening test. Differences in national healthcare administration warrants investigation into the resource impact of updating screening guidance in Canada. Methods: Microsimulation modeling was performed using OncoSim (version 3.6) to project health and economic outcomes of different CRC screening strategies based on Canadian population data. Four simulated birth cohorts of the Canadian population born between 1973–1992 were tracked for a 40-year span from the year the oldest in each cohort turned 40 until the youngest in the same cohort turned 75. Colorectal adenoma rates were adjusted according to cohort risk ratios estimated from historical incidence data to reflect real-world CRC rates. Outcomes were reported for the cumulative cohort. Results: Compared to FIT screening at age 50, FIT screening at 45 reduced deaths by 5,220, incidence by 11,980, and added 96,100 health-adjusted life years (HALY). Colonoscopy screening at age 45 led to 17,870 fewer deaths, 74,250 fewer cases and added 314,960 HALYs. FIT and colonoscopy screening at age 45 had incremental costs of CAD$3,259 and $7,881 per HALY gained vs. a FIT at age 50, respectively. Across screening strategies, the greatest benefits were observed in the youngest cohort. Colonoscopy screening at age 45 resulted in 10,679,540 more total colonoscopies than the current capacity of 8,966,979 with FIT screening at age 50. Lowering the screening age to 45 with a FIT increased colonoscopy demand by 329,555. The total cost of CRC care (screening, diagnosis and treatment) increased with lower screening ages and colonoscopy first modalities, while the cost of CRC management (diagnosis and treatment) decreased with lower screening ages and colonoscopy first approaches. Conclusions: Adjusting current CRC screening guidelines demonstrates significant resource implications with proportional health benefits. Lower screening ages and colonoscopy first approaches have the largest resource demand and greatest health outcomes, while the incremental cost per HALY gained for all screening strategies is modest compared to standard benchmarks. [Table: see text]
Clinicopathological features of post-colonoscopy colorectal cancer in patients with Japanese Lynch syndrome: A multicentric retrospective observational study.
Authors: Takao Akinari , Iizuka Toshiro , Takao Misato , Chino Akiko , Akagi Kiwamu , Yamada Masayoshi , Tanakaya Kohji , Ishida Hideyuki , Komori Koji , Sasaki Kazuhito , Miguchi Masashi , Hirata Keiji , Sudo Tomoya , Miyakura Yasuyuki , Ishikawa Toshiaki , Yamaguchi Tatsuro , Tomita Naohiro , Ajioka Yoichi 
Published: January 2024

79 Background: Due to the high incidence of heterochronic and concurrent colorectal cancer in Lynch syndrome (LS), colonoscopic surveillance is recommended in Japan every 1-2 years. Even with regular colonoscopic surveillance, post-colonoscopy colorectal cancer (PCCRC) often occurs in the intervals between surveillance, but there are currently no reports of the details of PCCRC in LS in Japan. Methods: Of 1756 colonoscopies performed between 2009 and 2018 in 316 patients with a diagnosis of LS confirmed by genetic testing who were enrolled in a nationwide, Japanese, multicentric study conducted by the Committee of Hereditary Colorectal Cancer of the Japanese Society for Cancer and Rectum, 1203 colonoscopies in 256 patients were assessed to determine the clinicopathological characteristics of PCCRC, after including cases of first-time surveillance, previously untreated lesions, and inadequate pretreatment. Then, the incidence of PCCRC was compared between patients with a median surveillance colonoscopy interval < 12 months (group A) and > 12 months (group B). Results: There were 49 cases of PCCRC with a total of 84 lesions. The number of lesions per tumor depth was 66, one, five, seven, four, and one for pTis, pT1, pT1a, pT1b, pT2, and pT3, respectively. Two (2.4%), 20 (23.8%), 21 (25%), four (4.8%), 18 (21.4%), and 19 (22.6%) lesions were localized in the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum, respectively. In pTis-pT1b, the macroscopic type was 0-IIa in 33 lesions (41.8%), 0-IIc in four lesions (5.1%), 0-IIa+IIc in five lesions (6.3%), 0-IIb in one lesion (1.3%), 0-Is in 15 lesions (19%), 0-Ip in one lesion (1.3%), 0-Isp in 16 lesions (20.3%), and unknown in four lesions. In pT1b-pT3, seven lesions (63.6%) were smaller than 20 mm. In terms of the median interval between surveillance colonoscopies, 130 patients had a median interval < 12 months (group A), and 126 patients had a median interval > 12 months (group B). In groups A and B, PCCRC, metachronous cases, simultaneous cases, and depths than pT1b were observed in 29 (22%) and 20 (16%) cases (p=0.21); 14 (11%) and two (1.6%) cases (p=0.006); six (4.6%) and one (0.8%) case (p=0.22), and six (4.6%) and four (3.2%) cases (p=1), respectively. Conclusions: In PCCRC in Lynch syndrome, invasive carcinomas < 2 cm should be noted. In addition, a surveillance interval of 12 months may be insufficient in patients with LS. Thus, further investigation is warranted.
Impact of the COVID-19 pandemic on colorectal cancer stage at presentation.
Authors: Squires Malcolm Hart , Lindolm Nicole , Shea Reilly , Donahue Erin E. , Wallander Michelle , Salo Jonathan C. 
Published: January 2024

80 Background: The primary study objective was to assess the impact of COVID-19 on the stage at presentation for patients with newly diagnosed colorectal cancer treated within a large cancer center network. Additionally, we aimed to evaluate differences in pathologic stage and treatment modality for patients diagnosed with colorectal cancer both immediately before and during the height of the COVID-19 pandemic. Methods: A retrospective analysis was performed on all subjects newly diagnosed with colorectal cancer between January 2019 and April 2021 at Levine Cancer Institute. Patients had a primary diagnosis of adenocarcinoma of the colon, rectum, or appendix. Patients were categorized into two cohorts based on date of diagnosis, with the pre-COVID-19 group diagnosed between January 2019 and February 2020 and the COVID-19 group diagnosed between March 2020 and April 2021. Chi-squared tests were used to evaluate the association between COVID-19 group and stage at presentation as well as pathologic stage. Results: A total of 1,190 patients were diagnosed with colorectal cancer within the study timeframe. Of the 613 patients diagnosed pre-COVID-19, 159 (25.9%) had metastatic disease at initial presentation. Comparatively, 577 patients were diagnosed during the COVID-19 study period, with 143 (24.8%) presenting with metastatic disease (p = 0.65).Of the 888 patients who presented with non-metastatic disease, 770 underwent primary surgical intervention for the initial treatment of their cancer, with 396 (87.2%) pre-COVID-19 and 374 (86.2%) COVID-19 patients receiving surgery (p = 0.65). Likewise, no significant difference was observed for T-classification, N-classification, or overall pathologic stage among patients undergoing surgical resection between the pre-COVID-19 and COVID-19 groups (p = 0.20; Table). Furthermore, amongst patients who presented with non-metastatic disease, chemotherapy was utilized for 200 (44.1%) patients diagnosed pre-COVID-19 and 190 (43.8%) patients diagnosed during COVID-19 (p = 0.93). Conclusions: We did not observe a significant difference in the proportion of patients presenting with metastatic colorectal cancer during COVID-19 versus those presenting pre-COVID-19. Furthermore, there was no significant difference observed among non-metastatic patients between the two groups for rates of initial surgical resection, pathologic stage, and treatment with chemotherapy. [Table: see text]
COLONTOWN Searching Safari: Education to remove barriers to pursue clinical trials for patients with metastatic colorectal cancer (mCRC).
Authors: Clauer Julie , Seybold Nancy , George Manju 
Published: January 2024

82 Background: Clinical trials can expand otherwise limited treatment options for patients with metastatic cancer. Yet, the complexity of the trial landscape can prevent patients from pursuing trials. Even in mCRC patients motivated to participate in trials, 79% described trial search negatively, mainly ‘overwhelming.’ We hypothesized that “clinical trial-literacy” and familiarity with the tools/process of pursuing trials were critical precursors for patients to incorporate trials into their treatment plan. To test this, we, as managers of COLONTOWN, a large, online CRC patient/caregiver community, developed an interactive course. Methods: We reviewed many posts from the COLONTOWN clinical trial groups to identify gaps between the desire to participate in a trial and the knowledge/tools needed to do so. We then determined those most likely to benefit as mCRC MSS patients interested in, but not in urgent need of, trials. We developed a 4-week long course with 5 hours of live online sessions and 5 hours of homework. Participants built fluency in the language of clinical trials, learned about available tools, and identified and assessed trials in the context of their personal needs and disease dynamics. Unlike most other trial resources, the focus was on informed patient-centered decision-making, not on the science or mechanics of trials. The course was offered 3 times in 2022/23 with iterative improvements after each session. Participants (n=48) were assessed for their attitudes around trials before and after the course to measure impact. Results: We found that our repeatable, scalable course improves mCRC patient perceptions of and skills to pursue trials as evidenced by pre-course vs. post-course surveys. This included average response to “How prepared do you feel to find a clinical trial?” increasing from 2.1 to 3.8 on a 5-pt scale and positive sentiment about the process rising from 7% to 71% (table). Positive feedback on meeting course objectives and amount of coursework being ‘just right’ (96% and 92% of responses, respectively) support the material’s value for time invested. Conclusions: Through systematic skill building, self reflection, and practical tools, our guided course can build confidence and empower patients and caregivers to take the next step to pursue clinical trials. Patient education can indeed help overcome often-overlooked emotional and knowledge barriers to pursuing clinical trials present even in a motivated patient population. Next, we plan to create and assess the benefit of an additional on-demand e-learning course and to expand to other patient groups. [Table: see text]
Associations of postdiagnosis changes in physical activity with all-cause mortality among patients with stage I-IIA colorectal cancer.
Authors: Smit Karel , Derksen Jeroen W.G. , van Lanen Anne-Sophie , Wesselink Evertine , Kok Dieuwertje E. , Kampman Ellen , van Duijnhoven Fränzel J.B. , Koopman Miriam , May Anne M. 
Published: January 2024

87 Background: Several observational studies show an association between physical activity (PA) at diagnosis and reduced risk of mortality among colorectal cancer (CRC) patients, but there has been limited research examining the potential benefit of changes in PA levels after CRC diagnosis. Here we investigate the association between change of PA and all-cause mortality in patients with stage I-IIA CRC receiving resection with curative intent. Methods: Data were used from two large Dutch CRC cohort studies (PLCRC & COLON), which assessed PA at diagnosis (T0), six (T6) and twelve (T12) months after diagnosis, using the SQUASH questionnaire. A total of 2540 stage I-IIA CRC patients with repeated PA measures (i.e. a T0 and at least a T6 or T12 questionnaire) were used for this analysis. Total PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week and categorized as low, moderate, and high PA, based on tertiles of an age- and sex-matched sample of the general population. PA changes were evaluated at T6 and T12 relative to T0. Being active was defined per timepoint as being in the moderate or high total PA group, or adhering to the PA guideline (minimum of 150 minutes per week of moderate-intensity PA). Cox proportional hazards models were used to study the association between PA variables and all-cause mortality, adjusted for age, sex, BMI, and tumor location (colon vs rectum). Results: Median follow-up time was 35 months (interquartile range 19 – 55) during which a total of 133 deaths occurred. Being active at both T0 and T6 compared to being inactive at these timepoints, was associated with a lower rate of all-cause mortality for both PA variables (adjusted hazard ratio (HR) 0.39 [95% confidence interval 0.24-0.63] and 0.41 [0.23-0.72] for total PA and guideline adherence, respectively). Similar results were found when comparing T12 to T0 (being active according to total PA HR 0.20 [0.09-0.42] and guideline adherence HR 0.31 [0.14-0.72]). Changing to either activity or inactivity at T6 or T12 was not significantly associated with all-cause mortality (Table). Conclusions: Maintaining a physically active lifestyle following surgery for stage I to IIA CRC is associated with longer overall survival, reinforcing the recommendations for physical activity. [Table: see text]