Epidemiological features and prognosis for primary gastrointestinal follicular lymphoma.

Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.

Prognostic significance of tumour budding in noncolorectal gastrointestinal tract and pancreatobiliary tract: a systematic review and meta-analysis.

Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta-analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle-Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta-analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21-5.04]), gastric adenocarcinoma (2.03 [1.38-2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02-3.25]), and biliary tract adenocarcinoma (3.11 [2.46-3.93]) with high-grade tumour budding. Additionally, high-grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility.

Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study.

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

The associations of food environment with gastrointestinal cancer outcomes in the United States.

BACKGROUND: Social conditions and dietary behaviors have been implicated in the rising burden of gastrointestinal cancers (GIC). The "food environment" reflects influences on a community level relative to food availability, nutritional assistance, and social determinants of health. Using the US Department of Agriculture-Food Environment Atlas (FEA), we sought to characterize the association of food environment on GIC presenting stage and long-term survival. METHODS: Patients diagnosed with GIC between 2013 and 2017 were identified using the SEER database. FEA-scores were based on 282 county-level food security variables, store-restaurant availability, SNAP/WIC enrollment, pricing/taxes, and producer vicinity adjusted-for factors of socioeconomic status, race-ethnicity, transportation access, and comorbidities. Relative FEA rankings across US counties were averaged into a composite score and assigned to patients by county-of-residence. The association of FEA, cancer stage, and survival were analyzed using multiple logistic regression and cox-proportional hazard models relative to White/non-White race/ethnicity. RESULTS: Among 287,148 patients, the most common GIC-sites were colon (n = 97,942, 34%), pancreas (n = 49,785, 17.3%), liver (n = 31,098, 11.0%) and esophagus (n = 16,271, 5.7%). A worse food environment was independently associated with increased odds of late-stage diagnosis (esophageal odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.01-1.05; hepatic OR: 1.06, 95% CI: 1.03-1.08; pancreatic OR: 1.04, 95% CI: 1.01-1.06) among all patients; in contrast, food environment was associated with colorectal cancer stage among non-White patients only (OR: 1.04, 95% CI: 1.03-1.06). Worse food environment was associated with worse 3-year survival (colon OR: 1.03, 95% CI: 1.01-1.04; hepatic OR: 1.12, 95% CI: 1.08-1.17; gastric OR: 1.07, 95% CI: 1.01-1.13). Similar associations were noted relative to overall survival among the entire cohort (biliary tract hazard ratio [HR]: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.02, 95% CI: 1.01-1.04; hepatic HR: 1.07, 95% CI: 1.06-1.09; pancreatic HR: 1.04, 95% CI: 1.02-1.05; rectum HR: 1.03, 95% CI: 1.01-1.04; gastric HR: 1.05, 95% CI: 1.03-1.07), as well as among non-White patients (biliary HR: 1.04, 95% CI: 1.01-1.07; colon HR: 1.03, 95% CI: 1.01-1.05; esophageal HR: 1.05, 95% CI: 1.02-1.08; hepatic HR: 1.08, 95% CI: 1.06-1.10) (all p < 0.003). CONCLUSIONS: Food environment was independently associated with late-stage tumor presentation and worse 3-year and overall survival among GIC patients. Interventions to address inequities across communities relative to food environments are needed to alleviate disparities in cancer care.

Adjuvant imatinib in high-risk resected gastrointestinal stromal tumors: Merely delaying the inevitable?

INTRODUCTION: Patients with high-risk resected gastrointestinal stromal tumors (GIST) receiving adjuvant imatinib have improved recurrence-free survival (RFS), however whether a complete cytocidal effect exists is unknown. We investigated this using a normalized recurrence timeline measured from end of oncologic treatment (EOOT), defined as the later of resection or end of adjuvant therapy. METHODS: We reviewed patients with resected high-risk GIST at our cancer center from 2003 to 2018. RFS (measured from resection and EOOT), overall survival (OS), and time to imatinib resistance (TTIR) were analyzed using Kaplan-Meier analysis and multivariable Cox proportional hazards modeling. The performance of the Memorial Sloan Kettering (MSK) GIST nomogram was assessed. RESULTS: We identified 86 patients with high-risk GIST with a median 106 months of postsurgical follow-up. One-third (n = 29; 34%) did not receive adjuvant imatinib, while 57 (66%) did for a median of 3 years. The MSK nomogram-predicted 5-year RFS for patients receiving adjuvant imatinib was similar to those who did not (29% vs. 31%, p = 0.64). When RFS was measured from EOOT, the MSK-predicted RFS was independently associated with EOOT RFS (hazard ratio 0.22, p = 0.02), while adjuvant imatinib receipt and duration were not. Neither receipt nor duration of adjuvant imatinib were associated with TTIR or OS (all p > 0.05). CONCLUSIONS: Treatment with adjuvant imatinib delays, but does not clearly impact ultimate recurrence, TTIR, or OS, suggesting many patients with high-risk GIST may receive adjuvant imatinib unnecessarily. Additional studies are needed to establish the benefit of adjuvant therapy versus initiating therapy at first radiographic recurrence.

Gastrointestinal cancer precursor risk and mortality in pancreatic intraductal papillary mucinous neoplasms: a nationwide cohort study.

BACKGROUND AND AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN. METHODS: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to ≤5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death. RESULTS: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths). CONCLUSIONS: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.

Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study.

INTRODUCTION: Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. PATIENTS: In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. RESULTS: The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. INTERPRETATION: A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

Baseline functioning scales of EORTC QLQ-C30 predict overall survival in patients with gastrointestinal cancer: a meta-analysis.

PURPOSE: A consensus has not been reached on the value of quality of life (QoL) as a prognostic factor for survival in gastrointestinal cancer. This meta-analysis aimed to investigate the association between functioning scales of the EORTC QoL Questionnaire Core 30 (QLQ-C30) and the overall survival (OS) in patients with gastrointestinal cancer. METHODS: A systematic literature search was conducted in PubMed, Web of Science, and Embase databases, until February 7, 2023. The studies included were those that investigated the association between baseline QoL measured by the functioning scales of EORTC QLQ-C30 and OS in patients with gastrointestinal cancer. The prognostic capacity of QoL was calculated by pooling the adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Twenty-four studies' analyses reported by 22 eligible articles involving 11,609 patients were included. When compared with good parameters of QoL, poor global QoL (HR 1.81; 95% CI 1.53-2.13), physical functioning (HR 1.51; 95% CI 1.31-1.74), social functioning (HR 1.67; 95% CI 1.30-2.15), and role functioning scale (HR 1.42; 95% CI 1.20-1.29) were significantly associated with decreased OS. For each 10-point increase in QLQ-C30 parameters, the pooled HR of OS was 0.87 (95% CI 0.83-0.92) for global QoL, 0.87 (95% CI 0.83-0.92) for physical functioning, and 0.93 (95% CI 0.88-0.97) for role functioning. However, each 10-point increase in social, emotional, or cognitive functioning scale did not significantly predict OS. CONCLUSIONS: Baseline health-related QoL defined by the physical functioning or global QoL scale of EORTC QLQ-C30 significantly predicts OS in patients with gastrointestinal cancer.

Comparing gastrointestinal stromal tumor outcomes between geriatric and non-geriatric patients: A population-based analysis.

BACKGROUND: Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the GI tract. SEER is an extensive cancer database which proves useful in analyzing population trends. This analysis investigated GIST outcomes between geriatric & non-geriatric patients. METHODS: SEER*STAT 8.4.0.1 was used to extract relevant GIST data from 2000 to 2019. Geriatric age was defined as ≥70 years. Variables included age, sex, surgery, cancer-specific death, and overall survival. Statistical tests included univariate analysis using KM survival estimate (95% confidence interval) to calculate 5-year survival (5YS). Log-Rank tests determined statistical significance. Multivariable Cox's PH regression estimated the geriatric hazard death ratio adjusted for sex, stage, and surgery. RESULTS: The number of patients included was 13,579, yielding overall 5YS of 68.6% (95% CI 67.7-69.5). Cancer-specific death was 39.11% in 2000 & 3.33% in 2019. Non-geriatric & geriatric patient data yielded 5YS of 77.4% (76.4%-78.3%) and 53.3% (51.7%-54.8%) respectively (p < 0.0001). For no surgery/surgery, younger patient data yielded 5YS of 48.7% (45.8%-51.4%) and 83.7% (82.7%-84.7%) respectively (p < 0.0001); geriatric data yielded 5YS of 29.3% (26.5%-32.1%) and 62.8% (60.8%-64.6%) respectively (p < 0.0001). Multivariable analysis yielded a geriatric hazard death of 2.56 (2.42-2.70) (p < 0.0001). CONCLUSIONS: Cancer-specific death decreased since 2000, indicating an improvement in survival & treatment methods. Observed lower survival rates overall in the geriatric group. Surgery appeared to enhance survival rates in both groups, suggesting that surgery is an important factor in GIST survival regardless of age. Large prospective studies will help define clinical management for geriatric patients.

A systematic review and meta-analysis of neoadjuvant imatinib use in locally advanced and metastatic gastrointestinal stromal tumors.

BACKGROUND: Several doubts remain regarding the optimal use of neoadjuvant imatinib in gastrointestinal stromal tumors (GISTs), such as ideal treatment duration, patient selection, and long-term survival outcomes. This manuscript provides a comprehensive review on neoadjuvant imatinib treatment outcomes and facilitate evidence-based decision-making for the use of imatinib therapy in GISTs. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to September 9, 2023. Meta-analyses of proportions were performed for the outcomes of R0 resection, disease responses, and 1-year, 3-year, and 5-year overall survival (OS) as well as 1-year, 3-year, and 5-year disease free survival (DFS). Sensitivity analyses in the form of leave-one-out analyses, meta-regression, and subgroup analyses were performed for outcomes with substantial statistical heterogeneity. RESULTS: The search yielded 1254 articles, and 36 studies were included in our analysis. Meta-analysis of proportions revealed that 1-year, 3-year, and 5-year OS was 100%, 94%, and 88%, while 1-year, 3-year and 5-year DFS was 99%, 89%, and 79%, respectively. An R0 resection rate of 89% and a disease response rate of 67% was achieved after a mean duration of treatment of 8.41 ± 0.367 months. KIT exon 9 mutation was significantly associated with poorer 5-year DFS. CONCLUSION: This study quantified key outcomes for neoadjuvant imatinib in locally advanced and metastatic or recurrent GIST. Patients with gastric and rectal tumous stand to benefit from neoadjuvant imatinib with an optimal treatment duration of 8 months. Furthermore, the potential utility of mutational analysis in guiding treatment with neoadjuvant imatinib was demonstrated.

Association of Remote Patient-Reported Outcomes and Step Counts With Hospitalization or Death Among Patients With Advanced Cancer Undergoing Chemotherapy: Secondary Analysis of the PROStep Randomized Trial.

BACKGROUND: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. OBJECTIVE: The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. METHODS: The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. RESULTS: Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively. CONCLUSIONS: In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054675.

Sarcopenia as a novel prognostic factor in the patients of primary localized gastrointestinal stromal tumor.

BACKGROUND: Sarcopenia predicts poor prognosis of a variety of gastrointestinal malignancies. However, there is a lack of study on the association between skeletal muscle index (SMI) and the prognosis of gastrointestinal stromal tumor (GIST). The aim of this study is to develop a novel nomogram based on sarcopenia for GIST patients to predict overall survival (OS). METHODS: SMI was measured by computed tomography scan of 107 patients who underwent resection for primary localized gastrointestinal stromal tumor (GIST). Sarcopenia was defined by cutoff values for SMI as 40.1 cm2/m2 and 39.8 cm2/m2 using optimum stratification for males and females respectively. Factors were included in the nomogram were specified by univariate and multiple Cox proportional hazard analysis. Concordance index (C-index) and calibration curves were conducted to measure the discrimination and accuracy of the nomogram. The utility of the nomogram was assessed by the decision curve analysis (DCA). RESULTS: Twenty-eight (26.2%) of 107 patients were sarcopenic. Sarcopenia was correlated significantly with body mass index, albumin, female sex, resection style, mitotic index, rupture status, survival. Sarcopenia was significantly related to decreased overall survival (p = 0.003).The nomogram including sarcopenia status, resection style and mitotic index had an excellent discrimination with C-index 0.794. The calibration curves represented a good accordance between the actual observation and nomogram prediction for overall survival. Decision curve analysis illustrated that the nomogram was helpful in clinic. CONCLUSIONS: We developed a nomogram based on sarcopenia to predict overall survival after resection of GISTs which is an effective and favorable prognostication tool.

Effectiveness of one-time endoscopic screening programme in prevention of upper gastrointestinal cancer in China: a multicentre population-based cohort study.

OBJECTIVES: To estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China. DESIGN: This multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group. RESULTS: Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively. CONCLUSION: Among individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality.

Disaggregated mortality from gastrointestinal cancers in Asian Americans: Analysis of United States death records.

Asian Americans (AAs) are heterogeneous, and aggregation of diverse AA populations in national reporting may mask high-risk groups. Gastrointestinal (GI) cancers constitute one-third of global cancer mortality, and an improved understanding of GI cancer mortality by disaggregated AA subgroups may inform future primary and secondary prevention strategies. Using national mortality records from the United States from 2003 to 2017, we report age-standardized mortality rates, standardized mortality ratios and annual percent change trends from GI cancers (esophageal, gastric, colorectal, liver and pancreatic) for the six largest AA subgroups (Asian Indians, Chinese, Filipinos, Japanese, Koreans and Vietnamese). Non-Hispanic Whites (NHWs) are used as the reference population. We found that mortality from GI cancers demonstrated nearly 3-fold difference between the highest (Koreans, 61 per 100 000 person-years) and lowest (Asian Indians, 21 per 100 000 person-years) subgroups. The distribution of GI cancer mortality demonstrates high variability between subgroups, with Korean Americans demonstrating high mortality from gastric cancer (16 per 100 000), and Vietnamese Americans demonstrating high mortality from liver cancer (19 per 100 000). Divergent temporal trends emerged, such as increasing liver cancer burden in Vietnamese Americans, which exacerbated existing mortality differences. There exist striking differences in the mortality burden of GI cancers by disaggregated AA subgroups. These data highlight the need for disaggregated data reporting, and the importance of race-specific and personalized strategies of screening and prevention.

The Impact of Prehabilitation on Patient Outcomes in Hepatobiliary, Colorectal, and Upper Gastrointestinal Cancer Surgery: A PRISMA-Accordant Meta-analysis.

OBJECTIVE: To determine the impact of prehabilitation on hospital length of stay, functional capacity, complications, and mortality after surgery in patients with hepatobiliary, colorectal, and upper gastrointestinal cancer. BACKGROUND: "Prehabilitation" encompasses exercise, nutrition, and psychosocial interventions to optimize health before surgery. The benefits of prehabilitation are ill-defined. METHODS: Medline, Embase and Cochrane Databases were searched systematically for the terms "prehabilitation AND exercise," "perioperative care AND cancer surgery," and "colorectal AND hepatobiliary AND hepatopancreatobiliary AND esophagogastric AND recovery AND outcomes." Primary outcomes analyzed were hospital length of stay, functional capacity, significant postoperative complications (Clavien Dindo ≥ III), and mortality. A meta-analysis was conducted on the effect of all-modality prehabilitation for patients with colorectal, hepatopancreatobiliary and upper gastrointestinal cancer surgery using the raw mean difference, risk difference, and a random-effects model. RESULTS: Three hundred and seventy seven original titles were identified. Fifteen studies (randomized controlled trials; n = 9 and uncontrolled trials; n = 6) were included in the meta-analysis. Prehabilitation reduced hospital length of stay by 1.78 days versus standard care (95% CI: -3.36, -0.20, P < 0.05). There was no significant difference in functional capacity with prehabilitation determined using the 6-minute walk test (P = 0.816) and no significant reduction in postoperative complications (P = 0.378) or mortality rates (P = 0.114). CONCLUSIONS: Prehabilitation was associated with reduced hospital length of stay but had no effect on functional capacity, postoperative complications, or mortality rates. Thus, prehabilitation should be recommended to accelerate recovery from cancer surgery, demonstrated by reduced hospital length of stay.

ITGA5 is a prognostic biomarker and correlated with immune infiltration in gastrointestinal tumors.

BACKGROUND: Integrin Subunit Alpha 5 (ITGA5), belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal tumors remain unclear. METHODS: The expression level of ITGA5 was detected by Oncomine and Tumor Immune Estimation Resource (TIMER). The association between ITGA5 and prognosis of patients was identified by Kaplan-Meier plotter, Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and PrognoScan. We evaluated the correlation between ITGA5 expression and immune infiltrating level via TIMER. Besides, TIMER, immunohistochemistry (IHC) staining and western blot were used to explore correlations between ITGA5 expression and markers of immune infiltrates cells. Furthermore, we constructed protein-protein interaction (PPI) network and performed functional enrichment by GeneMANIA and Metascape. RESULTS: ITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of gastrointestinal tumors. In addition, ITGA5 expression level was significantly associated with tumor purity and immune infiltration levels of different immune cells in gastrointestinal tumors. Interestingly, immune markers for monocytes, tumor - associated macrophages (TAMs), macrophages 2 (M2) cells and T-helper 2 (Th2) cells were found to be significantly and positively correlated with ITGA5 expression levels in colon and gastric cancer. Results from IHC staining and western blot further proved that markers of Th2 and M2 cell were significantly increased in gastric cancer patients with high ITGA5 expression levels. Lastly, interaction network and function enrichment analysis revealed ITGA5 was mainly involved in "integrin mediated signaling pathway", "leukocyte migration", "cell-substrate adhesion". CONCLUTIONS: Our study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in gastrointestinal tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations.

Tumor response as defined by iRECIST in gastrointestinal malignancies treated with PD-1 and PD-L1 inhibitors and correlation with survival.

BACKGROUND: Atypical tumor response patterns during immune checkpoint inhibitor therapy pose a challenge to clinicians and investigators in immuno-oncology practice. This study evaluated tumor burden dynamics to identify imaging biomarkers for treatment response and overall survival (OS) in advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors. METHODS: This retrospective study enrolled a total of 198 target lesions in 75 patients with advanced gastrointestinal malignancies treated with PD-1/PD-L1 inhibitors between January 2017 and March 2021. Tumor diameter changes as defined by immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) were studied to determine treatment response and association with OS. RESULTS: Based on the best overall response, the tumor diameter ranged from - 100 to + 135.3% (median: - 9.6%). The overall response rate was 32.0% (24/75), and the rate of durable disease control for at least 6 months was 30.7% (23/75, one (iCR, immune complete response) or 20 iPR (immune partial response), or 2iSD (immune stable disease). Using univariate analysis, patients with a tumor diameter maintaining a < 20% increase (48/75, 64.0%) from baseline had longer OS than those with ≥20% increase (27/75, 36.0%) and, a reduced risk of death (median OS: 80 months vs. 48 months, HR = 0.22, P = 0.034). The differences in age (HR = 1.09, P = 0.01), combined surgery (HR = 0.15, P = 0.01) and cancer type (HR = 0.23, P = 0.001) were significant. In multivariable analysis, patients with a tumor diameter with a < 20% increase had notably reduced hazards of death (HR = 0.15, P = 0.01) after adjusting for age, combined surgery, KRAS status, cancer type, mismatch repair (MMR) status, treatment course and cancer differentiation. Two patients (2.7%) showed pseudoprogression. CONCLUSIONS: Tumor diameter with a < 20% increase from baseline during therapy in gastrointestinal malignancies was associated with therapeutic benefit and longer OS and may serve as a practical imaging marker for treatment response, clinical outcome and treatment decision making.

Association between time to stent dysfunction and the anti-tumour effect of systemic chemotherapy following stent placement in patients with pancreaticobiliary cancers and malignant gastric outlet obstruction: a retrospective cohort study.

BACKGROUND: Malignant gastric outlet obstruction (MGOO) occasionally occurs due to pancreaticobiliary cancer. Endoscopic duodenal stenting (DS) is a common treatment for MGOO. However, it has been reported that DS does not have sufficient patency time for it to be used in patients who have a potentially increased lifespan. Nowadays, systemic chemotherapy for pancreaticobiliary cancer has developed, and its anti-tumour effect would make time to stent dysfunction longer. Therefore, we retrospectively evaluated the association between objective response to systemic chemotherapy, followed by DS and time to stent dysfunction in patients with advanced pancreaticobiliary cancer. METHODS: This retrospective study included 109 patients with advanced pancreaticobiliary cancer who received systemic chemotherapy after DS. Patients who showed complete or partial response were defined as responders. The rest were defined as non-responders. Time to stent dysfunction was compared between responders and non-responders using the landmark analysis at 2 months after DS. Death without recurrence of MGOO was considered as a competing risk for time to stent dysfunction. RESULTS: Combination and monotherapy regimens were adopted for 46 and 63 patients, respectively. Median progression-free survival and overall survival were 3.2 months (95% confidence interval [CI], 2.4-4.0) and 6.0 months (95% CI, 4.6-7.3). Objective response was observed in 21 patients (19.3%). Median time to stent dysfunction was 12.5 months (95% CI, 8.4-16.5) in the entire cohort. In 89 patients, responders had a lower cumulative incidence of stent dysfunction than non-responders: 9.5 and 19.1% at 6 months, and 19.0 and 27.9% at 1-year, respectively. There was difference of time to stent dysfunction between responders and non-responders among patients who received combination regimen as the first-line treatment with p-value of 0.009: cumulative incidence was 0 and 42.9% at 6 months, and 9.3 and 57.1% at 1-year, respectively. CONCLUSIONS: Longer time to stent dysfunction is expected when systemic chemotherapy following DS suppresses tumour progression; DS is slated to be a standard treatment for MGOO even in patients with pancreaticobiliary cancer and a long lifespan.

Imatinib-induced pancreatic hypertrophy in patients with gastrointestinal stromal tumor: Association with overall survival.

OBJECTIVES: To investigate the frequency of imatinib-induced pancreatic complications and determine whether these are survival prognostic factors in patients with gastrointestinal stromal tumor (GIST). METHODS: This retrospective multicenter study included patients with histopathologically diagnosed GIST treated with imatinib who underwent computed tomography (CT) within 100 days before (pretreatment CT) and 500 days after (post-treatment CT) imatinib initiation (January 2004-December 2019). Forty-eight patients (63.0 ± 12.1 years, 30 men) were included. Two blinded radiologists independently measured pancreatic volumes. Pancreatic volume on pretreatment CT was compared with that of the control (within 1 year prior to pretreatment CT) and the first two post-treatment CTs using paired t-tests. Thresholds for pancreatic hypertrophy and atrophy were defined using a log-rank test. The prognostic importance of pancreatic hypertrophy was further analyzed using multivariate Cox proportional hazard regression models. RESULTS: Pancreatic volume was significantly higher for the first post-treatment CT than pretreatment CT (71.5 cm3 vs. 67.4 cm3, P = .027), whereas no significant difference was observed between the pretreatment and control CTs. Optimal thresholds for pancreatic hypertrophy and atrophy were defined as an 22% increase and 30% decrease and found in 20 and three patients, respectively. Pancreatic hypertrophy was significantly associated with reduced survival [hazard ratio = 2.9 (95% confidence interval, 1.3-6.5), P = .0088]. No patients showed serum lipase elevation, nor were they suspected of having acute pancreatitis. CONCLUSION: There was frequent asymptomatic pancreatic swelling in patients with GIST after imatinib treatment, and a ≥22% increase in pancreatic volume was a predictor of reduced survival.

Functional Impairments and Quality of Life in Older Adults With Upper Gastrointestinal Cancers.

BACKGROUND: Functional impairments (measured by activities of daily living [ADLs]) and health-related quality of life (HRQOL) may complicate outcomes in older adults diagnosed with cancer. In this retrospective cohort analysis, we characterized ADLs and HRQOL in adults older than 65 y with upper gastrointestinal (UGI) cancers and evaluated for an association to cancer-specific survival. MATERIALS AND METHODS: Patients with UGI cancers aged 65 y or older were selected from the Surveillance, Epidemiology and End Results and the Medicare Health Outcomes Survey-linked database. Demographics, comorbidities, stage, ADLs, and HRQOL were summarized by patients managed with and without surgery. Because of the wide variety of cancers, we subdivided patients into cohorts of esophagogastric [EG; n = 88] or hepatobiliary/pancreatic [n = 68]. Cancer-specific survival curves were modeled for changes in ADL and HRQOL scores after diagnosis. Risk factors for cancer-specific survival were assessed with hazard ratios (HRs) and adjusted for demographics, stage, comorbidities, and disease cohorts. RESULTS: HRQOL scores declined after diagnosis, with a sharper decline in nonsurgery patients. On multivariate analysis, inability to perform specific ADLs was associated with worse survival in multiple cohorts: hepatobiliary/pancreatic nonsurgery patients unable to eat (HR 3.3 95% confidence interval (CI) 1.7-6.5); all patients with EG unable to use the toilet (HR 3.3 95% CI 1.5-7.9); EG nonsurgery cohort unable to dress or use the toilet (dress HR 14.1 95% CI 4.0-49.0; toilet HR 4.7 95% CI 1.8-12.3). CONCLUSIONS: Older survivors with UGI cancers report declines in HRQOL, especially those not undergoing surgery. The ability to perform ADLs may be linked to survival in this population.