Upper Gastrointestinal Cancer Research Articles

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.

Barriers to upper gastrointestinal screening among the general population in high-prevalence areas: a cross-sectional study.

In China, there are large differences between regions in the use of gastroscopies and public awareness of upper gastrointestinal (UGI) screening. This study investigated the current context and analyzed the barriers that influence UGI screening behavior among the general population in UGI cancer high-prevalence areas. A total of 320 participants anonymously answered an online questionnaire. The rank sum test was used to analyze the difference in the scores of the UGI screening awareness questionnaire among participants with different socio-demographic characteristics. Using the awareness level of UGI screening and gastroscopy as the dependent variable, and the socio-demographic characteristics as the independent variable, simple linear regression and binary logistic regression analysis were used to determine the factors influencing attitudes toward gastroscopy screening. We used Spearman's correlation analysis to examine the correlation between UGI screening awareness level and willingness to undergo a gastroscopy. There was a correlation between the willingness to undergo gastroscopy and the awareness level of UGI screening (r = 0.243, p < 0.001). Linear regression analysis found that age, type of residence, education level, employment status, monthly income, history of gastroscopy, dietary habits, physical exercise, and convenience in obtaining information were significantly correlated with the awareness level of UGI screening ( p < 0.05). Binary logistic regression analysis found that factors significantly associated with gastric cancer screening behavior include residence, monthly income, and self-perceived health status ( p < 0.05). It is necessary to improve education about UGI cancer and screening knowledge, with a focus on populations with lower education and income.

PREHABILITATION BEFORE GASTROINTESTINAL CANCER SURGERY (PREHAB-GI): AN IMPLEMENTATION STUDY

BACKGROUND Surgery continues to be the primary treatment option for early-stage colorectal and upper gastrointestinal (UGI) cancers. However, up to 30-40% will experience a major complication. Prehabilitation aims to improve preoperative functional reserves through physical, nutritional, and/or psychological interventions. We aimed to evaluate the implementation of a multimodal prehabilitation program in gastrointestinal cancer surgery patients. METHODS A single-arm implementation study using a pre-post design. Colorectal or UGI cancer patients scheduled for curative intent surgery at Concord Hospital with ≥14 days pre-surgery were recruited. The intervention was face-to-face or by telehealth (COVID adaptations): a 2-4-week program consisting of i) supervised exercise, ii) dietary education and protein supplements, iii) nursing support. The primary outcome was implementation using the RE-AIM (Reach/Effectiveness/Adoption/Implementation/Maintenance) framework. Secondary outcomes included functional, nutritional, and surgical outcomes. RESULTS Over 16 months, 181 were screened; 95 (52%) were eligible. Reach: 77/95 recruited (64 colorectal, 13 UGI). The median age was 70 years; 46 (60%) were males. Median intervention duration was 16 days. Effectiveness: Functional capacity using the 6-minute walk test and 2-minute step test improved from baseline to pre-surgery; 9.3m (p=0.038) and 6.5 steps (p=&amp;lt;0.001), respectively. Self-reported moderate, vigorous and resistance training statistically increased from baseline to pre-surgery. Hospital length of stay decreased by 1.9 days (p=0.010). There was no difference in total complications and readmissions. Adoption: 91% of referrals were directly from surgeons. Implementation: 72 completed the intervention; 5 withdrew after baseline assessment. 34% of assessments and intervention were delivered by telehealth. Adherence to the intervention was high; 94% exercise, 97% nutrition, 98% nursing. Overall, participant and clinician satisfaction was high. Maintenance: The program has been adopted as standard care with modifications post-study completion. CONCLUSIONS Our study shows that multimodal prehabilitation can be successfully implemented in a real-world setting, with a trend to improve functional and surgical outcomes.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor + chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers.

The combination of programmed cell death protein-1 (PD-1) inhibitor and chemotherapy is approved as a standard first- or second-line treatment in patients with advanced oesophageal or gastric cancer. However, it is unclear whether this combination is superior to chemotherapy alone. To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal carcinoma. We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer. We employed either random or fixed models to analyze the outcomes of each clinical trial, encompassing data on overall survival (OS), progression-free survival (PFS), objective response rate, and adverse events (AEs). Nine phase 3 clinical trials (7016 advanced oesophageal and gastric cancer patients) met the inclusion criteria. Our meta-analysis demonstrated that the pooled PD-1 inhibitor + chemotherapy group had a significantly longer OS than the chemotherapy-alone group [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.71-0.81]; the pooled PFS result was consistent with that of OS (HR = 0.67, 95%CI: 0.61-0.74). The count of patients achieving an objective response in the PD-1 inhibitor + chemotherapy group surpassed that of the chemotherapy-alone group [odds ratio (OR) = 1.86, 95%CI: 1.59-2.18]. AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group, regardless of whether ≥ grade 3 only (OR = 1.30, 95%CI: 1.07-1.57) or all AE grades (OR = 1.88, 95%CI: 1.39-2.54) were examined. We performed a subgroup analysis based on the programmed death-ligand 1 (PD-L1) combined positive score (CPS) and noted extended OS and PFS durations within the CPS ≥ 1, CPS ≥ 5, and CPS ≥ 10 subgroups of the PD-1 inhibitor + chemotherapy group. In contrast to chemotherapy alone, the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer, GEJ tumor, or oesophageal cancer. This holds true particularly for individuals with PD-L1 CPS scores of ≥ 5 and ≥ 10.

Anaerobic gram-negative rod bacteremia as a marker of gastrointestinal cancer in Japanese patients: a single-center retrospective study.

Gram-negative rod (GNR) bacteremia has been suggested as a clinical marker of occult cancer; however, no studies are available in this regard in the Japanese population. Here, we investigated the risk factors for gastrointestinal cancer with GNR bacteremia. Patients with GNR bacteremia admitted to St. Luke's International Hospital between January 2011 and July 2021 were included. The clinical data of patients with and without cancer, 1 year before and after GNR bacteremia diagnosis, were compared. Univariate analysis was performed using χ2 and Fisher's exact tests for categorical variables and the Mann-Whitney U test for continuous variables, while multivariable analysis was performed using logistic regression analysis, and a P of <0.05 was considered statistically significant. Of 2,296 GNR bacteremia-positive patients, 96 were associated with gastrointestinal cancer, and univariate analysis showed significant differences between the gastrointestinal cancer and comparison groups in terms of mean body mass index (BMI; 20.5 vs. 21.8 kg/m2 ), Enterobacterales detection (64.6% vs. 81.3%), and anaerobic GNR detection (24.0% vs. 8.5%). Thirty-five (36%) and 61 (64%) patients had upper and lower gastrointestinal cancer, respectively. There were 23 patients with anaerobic GNR bacteremia related to 24 strains (upper and lower gastrointestinal cancer, 5 and 18 cases, respectively). Multivariate analysis identified anaerobic GNR [odds ratio, 3.440; 95% confidence interval (CI): 2.085-5.675, P<0.001] as a significant risk factor for cancer. Anaerobic GNR in blood cultures may be a risk factor for gastrointestinal cancer. Therefore, it is necessary consider cancer workup, such as endoscopy, for patients with anaerobic GNR bacteremia.

Employment status in cancer patients the first five years after diagnosis-a register-based study.

Work is important for identity formation, social status, and economic independency. Although some evidence within the field of work and cancer survivorship exists, no study has so far investigated employment status across all cancer diagnoses. Thus, the aim of the present study was to investigate the impact of all cancer diagnoses on employment status. Danish cancer patients aged 20-60years, diagnosed between 2000 and 2015, were identified through Danish registers and matched 1:5 with cancer-free controls. Logistic and linear regression was performed separately in 11 cancer types to assess and compare work status and work participation between cancer patients and cancer-free controls one, three, and five years after diagnosis. A total of 111,770 cancer patients and 507,003 cancer-free controls were included. All cancer types had lower chances of working one year after diagnosis (ORs between 0.05 and 0.76), with lung, colorectal, upper gastrointestinal, and blood cancer patients having the lowest chances. After three years, 10 of 11 cancer types had lower chances (ORs between 0.39 and 0.84). After five years, there were minimal differences between cancer patients and controls among most cancer types (ORs between 0.75 and 1.36). Most cancer patients had lower chances of working compared with the general population until five years after diagnosis. However, patients with certain cancer types experienced lower chances of working all years, despite improvement over time. The knowledge will help increase awareness on challenges regarding work-life after cancer. Furthermore, the distinguishing between diagnoses can inform to more targeted vocational rehabilitation.

Vagus nerve signal has an inhibitory influence on the development of peritoneal metastasis in murine gastric cancer

The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.

Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism

BackgroundDirect oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. MethodsUsing the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N=88; lower GI cancer: N=114; non-GI cancer: N=947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. ResultsThe upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4%, lower GI cancer: 15.4%, and non-GI cancer: 11.6%, P=0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53%), followed by the lower GI (24%). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95%CI, 1.31-3.87, P=0.003), but that in lower GI cancer was insignificant. ConclusionsUpper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs.Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htmUnique identifier: UMIN000044816.

Risk of cancers proximal to the colon in fecal immunochemical test positive screenees in a colorectal cancer screening program

In more than half of the colorectal cancer (CRC) screening participants with a positive fecal immunochemical test (FIT) result, no advanced neoplasia (AN) is detected at colonoscopy. The positive FIT result could also be generated by cancers located proximal to the colon: upper gastrointestinal, oral cavity, nose and throat cancers. We evaluated screenees' risk of being diagnosed with a cancer proximal to the colon within the three years and compared risks between those with a positive versus those with a negative FIT. Data of Dutch CRC screening participants who underwent biennial FIT-based screening 2014-2018 were collected from the national screening database and linked to the National Cancer Registry. Screenees were classified into three groups: FIT-positives with AN (FIT+/AN+), FIT-positives without AN (FIT+/AN-) and FIT-negatives (FIT-). We compared the cumulative incidence of cancers proximal to the colon in each group three years after FIT. A Cox regression analysis with left truncation and right censoring, using FIT positivity as time-dependent variable and stratified for sex, was performed to compare the hazard of cancers proximal to the colon in FIT-positives versus FIT-negatives. Three-year cumulative incidence of cancers proximal to the colon in FIT+/AN+ (n=65,767), FIT+/AN- (n=50,661) and FIT- (n=1,831,647) screenees was 0.7%, 0.6% and 0.4%, respectively (p<0.001). FIT-positives were older and more frequently male than FIT-negatives (p<0.001). Significantly more cancers proximal to the colon were detected among FIT-positives (p<0.001; hazard ratio 1.55, 95% CI: 1.44 to 1.67). FIT-positive screenees were at significantly increased risk of being diagnosed with a cancer proximal to the colon within three years after FIT, though the three-year cumulative incidence was still less than one percent.

Survival in esophageal cancer with nonregional lymphadenopathy: a propensity score–matched analysis

BackgroundSurvival among esophageal cancer patients with stage IV non-regional lymphadenopathy treated with neoadjuvant therapy and surgical resection is not well described. This study aimed to compare the survival outcomes of patients with non-regional lymphadenopathy with a propensity matched cohort of patients with loco-regional disease. MethodsA retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada was performed. From 01/2010 until 12/2022, patients with radiologically suspicious non-regional retroperitoneal or supraclavicular lymphadenopathy were identified. Using 1:1 propensity score matching, a control group without non-regional disease was created. ResultsOf the 1235 patients identified, 39 met the inclusion criteria and were allocated to the study group of whom 35/39 (89%) had adenocarcinoma. Retroperitoneal and supraclavicular lymphadenopathy occurred in 26/39 (67%) and 13/39 (33%). Thirty-four received neoadjuvant chemotherapy (87%) and 5/39 (13%) chemoradiotherapy. Following resection, ypN0 of non-regional lymph node stations occurred in 21/39 (54%). When comparing the study group with a matched non-Stage IV control group, median overall survival was similar in patients with retroperitoneal lymphadenopathy (21 months, 95% CI 8-21 vs 27.0, 95% CI 13-41 p=0.262) but not with supraclavicular disease (13 months, 95% CI 8-18,p=0.039). Median follow up was 40.1 months (95% CI 1-83) and 70.0 (95% CI 33-106) for the study and control groups. ConclusionsCompared to a matched cohort of patients with similar disease burden but not stage IV disease, retroperitoneal lymphadenopathy did not negatively affect survival outcomes. Multimodal curative intent therapy may be appropriate in select cases.

Nationwide Association of Surgical Performance of Minimally Invasive Esophagectomy With Patient Outcomes

Suboptimal surgical performance is hypothesized to be associated with less favorable patient outcomes in minimally invasive esophagectomy (MIE). Establishing this association may lead to programs that promote better surgical performance of MIE and improve patient outcomes. To investigate associations between surgical performance and postoperative outcomes after MIE. In this nationwide cohort study of 15 Dutch hospitals that perform more than 20 MIEs per year, 7 masked expert MIE surgeons assessed surgical performance using videos and a previously developed and validated competency assessment tool (CAT). Each hospital submitted 2 representative videos of MIEs performed between November 4, 2021, and September 13, 2022. Patients registered in the Dutch Upper Gastrointestinal Cancer Audit between January 1, 2020, and December 31, 2021, were included to examine patient outcomes. Hospitals were divided into quartiles based on their MIE-CAT performance score. Outcomes were compared between highest (top 25%) and lowest (bottom 25%) performing quartiles. Transthoracic MIE with gastric tube reconstruction. The primary outcome was severe postoperative complications (Clavien-Dindo ≥3) within 30 days after surgery. Multilevel logistic regression, with clustering of patients within hospitals, was used to analyze associations between performance and outcomes. In total, 30 videos and 970 patients (mean [SD] age, 66.6 [9.1] years; 719 men [74.1%]) were included. The mean (SD) MIE-CAT score was 113.6 (5.5) in the highest performance quartile vs 94.1 (5.9) in the lowest. Severe postoperative complications occurred in 18.7% (41 of 219) of patients in the highest performance quartile vs 39.2% (40 of 102) in the lowest (risk ratio [RR], 0.50; 95% CI, 0.24-0.99). The highest vs the lowest performance quartile showed lower rates of conversions (1.8% vs 8.9%; RR, 0.21; 95% CI, 0.21-0.21), intraoperative complications (2.7% vs 7.8%; RR, 0.21; 95% CI, 0.04-0.94), and overall postoperative complications (46.1% vs 65.7%; RR, 0.54; 95% CI, 0.24-0.96). The R0 resection rate (96.8% vs 94.2%; RR, 1.03; 95% CI, 0.97-1.05) and lymph node yield (mean [SD], 38.9 [14.7] vs 26.2 [9.0]; RR, 3.20; 95% CI, 0.27-3.21) increased with oncologic-specific performance (eg, hiatus dissection, lymph node dissection). In addition, a high anastomotic phase score was associated with a lower anastomotic leakage rate (4.6% vs 17.7%; RR, 0.14; 95% CI, 0.06-0.31). These findings suggest that better surgical performance is associated with fewer perioperative complications for patients with esophageal cancer on a national level. If surgical performance of MIE can be improved with MIE-CAT implementation, substantially better patient outcomes may be achievable.

The Use of Natural Language Processing Elements for Computer-Aided Diagnostics and Monitoring of Body Image Perception in Enterally Fed Patients with Head and Neck or Upper Gastrointestinal Tract Cancers.

Psycho-oncology care has emerged as a significant concern in contemporary oncology practice, given its profound impact on patient psychological well-being. Patients undergoing treatment for head-neck or upper gastrointestinal tract cancers often experience complex emotional and psychological challenges, necessitating specialized support and intervention. Traditional approaches to psycho-oncological care may be limited in their ability to comprehensively assess and address patients' needs. Therefore, exploring innovative methodologies, such as leveraging natural language processing (NLP) elements, is crucial to enhancing the effectiveness of psycho-oncological interventions. In this study, we developed a method utilizing natural language processing (NLP) elements to augment psycho-oncological care for patients with head-neck or upper gastrointestinal tract cancers. The method aimed to facilitate vocabulary, sentiment, and intensity analysis of five basic emotions (happiness, sadness, anger, disgust, and fear), as well as to explore potential areas of difficulty such as body image, pain, and self-esteem. We conducted research involving 50 patients across three treatment stages. Our method facilitated the identification of characteristic features at each treatment stage, aiding in the tailoring of appropriate therapies to individual patient needs. The results offer insights valuable to psychologists and psychiatrists for expedited diagnosis and intervention, potentially influencing therapy outcomes. Additionally, the data may inform treatment decisions by addressing patient-specific concerns. Furthermore, our method holds promise for optimizing the allocation of psychological care resources, particularly at the initial stages of patient contact. The main problem in the research was the fairly wide age range of participants, which explains the potential diversity of vocabulary. In conclusion, our study demonstrates the potential utility of integrating natural language processing (NLP) elements into psycho-oncological care for patients with head-neck or upper gastrointestinal tract cancers. The developed method offers a novel approach to comprehensively assessing patients' emotional states and areas of difficulty, thereby facilitating tailored interventions and treatment planning. These findings underscore the importance of continued research and innovation in psycho-oncology to enhance patient care and outcomes.

Metabolites, Healthy Lifestyle, and Polygenic Risk Score Associated with Upper Gastrointestinal Cancer: Findings from the UK Biobank Study.

Previous metabolomics studies have highlighted the predictive value of metabolites on upper gastrointestinal (UGI) cancer, while most of them ignored the potential effects of lifestyle and genetic risk on plasma metabolites. This study aimed to evaluate the role of lifestyle and genetic risk in the metabolic mechanism of UGI cancer. Differential metabolites of UGI cancer were identified using partial least-squares discriminant analysis and the Wilcoxon test. Then, we calculated the healthy lifestyle index (HLI) score and polygenic risk score (PRS) and divided them into three groups, respectively. A total of 15 metabolites were identified as UGI-cancer-related differential metabolites. The metabolite model (AUC = 0.699) exhibited superior discrimination ability compared to those of the HLI model (AUC = 0.615) and the PRS model (AUC = 0.593). Moreover, subgroup analysis revealed that the metabolite model showed higher discrimination ability for individuals with unhealthy lifestyles compared to that with healthy individuals (AUC = 0.783 vs 0.684). Furthermore, in the genetic risk subgroup analysis, individuals with a genetic predisposition to UGI cancer exhibited the best discriminative performance in the metabolite model (AUC = 0.770). These findings demonstrated the clinical significance of metabolic biomarkers in UGI cancer discrimination, especially in individuals with unhealthy lifestyles and a high genetic risk.

Prevalence of and Factors Associated with Financial Toxicity After Pancreatectomy and Gastrectomy.

Financial toxicity (FT) refers to the adverse impact of cancer treatment costs on patients' experiences, potentially leading to poor adherence to treatment and outcomes. However, the prevalence of FT among patients undergoing major upper gastrointestinal cancer operations, as well as factors associated with FT, remain unclear. We conducted a cross-sectional study by sending the Comprehensive Score for financial Toxicity (COST) survey and Surgery-Q (a survey specifically developed for this study) to patients who underwent gastrectomy or pancreatectomy for malignant disease at our institution in 2019-2021. We sent the surveys to 627 patients and received responses from 101 (16%) patients. The FT prevalence (COST score <26) was 48 (48%). Patients likely to experience FT were younger than 50years of age, of non-White race, earned an annual income <$75,000, and had credit scores <740 (all p<0.05). Additionally, longer hospital stay (p=0.041), extended time off work for surgery (p=0.011), and extended time off work for caregivers (p=0.005) were associated with FT. Procedure type was not associated with FT; however, patients who underwent minimally invasive surgery (MIS) had a lower FT probability (p=0.042). In a multivariable analysis, age <50years (p=0.031) and credit score <740 (p<0.001) were associated with high FT risk, while MIS was associated with low FT risk (p=0.024). Patients with upper gastrointestinal cancer have a major risk of FT. In addition to predicting the FT risk before surgery, facilitating quicker functional recovery with the appropriate use of MIS is considered important to reducing the FT risk.

Comparison of Goal Achievement during an Early, Intensive Nutrition Intervention Delivered to People with Upper Gastrointestinal Cancer by Telephone Compared with Mobile Application.

This study is aimed at exploring whether the mode of nutrition intervention delivery affected participant goal achievement in a three-arm randomised controlled trial of early and intensive nutrition intervention delivered to upper gastrointestinal cancer patients. Newly diagnosed upper gastrointestinal cancer patients were recruited from four tertiary hospitals in Melbourne, Australia. Participants in the intervention groups received a regular nutrition intervention for 18 weeks from an experienced dietitian via telephone or mobile application (app) using behaviour change techniques to assist in goal achievement. Univariate and multiple regression models using STATA determined goal achievement, dose, and frequency of contact between groups. A p value <0.05 was considered statistically significant. The telephone group (n = 38) had 1.99 times greater frequency of contact with the research dietitian (95% CI: 1.67 to 2.36, p < 0.001) and 2.37 times higher frequency of goal achievement (95% CI: 1.1 to 5.11, p = 0.03) compared with the mobile app group (n = 36). The higher dose (RR 0.03) of intervention and more behaviour change techniques employed in the telephone group compared with the mobile app group increased participant goal achievement (95% CI: 0.01 to 0.04, p < 0.001). Discussion. Telephone nutrition intervention delivery led to a higher frequency of goal achievement compared to the mobile app intervention. There was also a higher number of behaviour change techniques employed which may have facilitated the greater goal achievement. Mobile app-based delivery may have poorer acceptance in this population with high levels of withdrawal. Practice Implications. We need to ensure that specifically designed technologies for our target populations are fit for purpose, efficacious, and acceptable to both patients and healthcare providers. This trial is registered with ACTRN12617000152325.

Abstract 4744: Overcoming MK1775 resistance in upper gastrointestinal cancers with combined WEE1 and CHK1 inhibition

Abstract Background: Upper gastrointestinal cancers (UGC), encompassing esophageal and gastric cancers, rank among the top causes of cancer-related deaths globally, with esophageal cancer being the sixth and gastric cancer the fourth leading cause. Esophageal adenocarcinoma (EAC), predominant in the western world, shares histopathological and molecular characteristics with gastric cancer (GC). Despite these similarities, treatment challenges persist, exemplified by the limited efficacy of the WEE1 inhibitor MK1775 in clinical trials due to drug resistance. Our study investigates novel mechanisms underlying this resistance in UGC. Methods and results: RNA sequencing and immunohistochemistry staining demonstrated notable overexpression of WEE1 in over two hundred human EAC and GC samples compared to normal tissues. Concurrently, Western blot analysis revealed a positive correlation between WEE1 and CHK1 overexpression across 16 UGC cell lines. To categorize UGC cells based on their sensitivity to MK1775, we conducted ATP-glo cell viability assays, determining their half-maximal inhibitory concentration (IC50) values. Utilizing nuclear-cytosol separation, our data intriguingly uncovered, for the first time, that in MK1775-resistant cells, MK1775 treatment induces the abnormal translocation of phosphorylated CHK1 (p-CHK1) from the nucleus to the cytoplasm, a shift not observed in MK1775-sensitive cells. Further analysis through Western blot suggested that the cytoplasmic presence of p-CHK1 might trigger the activation of oncogenic STAT3 following MK1775 treatment. This activation appears to stimulate the expression of genes that promote cancer cell survival and drug resistance by enhancing cell survival and inhibiting apoptosis. Notably, combining the WEE1 inhibitor with the CHK1 inhibitor CHIR124 effectively inhibited CHK1 kinase activity and abrogated STAT3 phosphorylation, DNA binding, and transcriptional activity in UGC cells. Our findings strongly indicate that a combined therapy of WEE1 and CHK1 inhibitors could be a promising strategy to overcome MK1775 resistance in UGC cells. Our ongoing research will employ human-derived UGC organoids, patient-derived xenografts (PDXs), and human tissue samples to further validate these findings. Conclusions: Our study underscores the potential of combining WEE1 and CHK1 inhibitors to effectively combat MK1775 resistance in UGC, offering a promising direction for improved treatment strategies and patient outcomes in these challenging malignancies. Citation Format: Krishnapriya Thangaretnam, MD Obaidul Islam, Heng Lu, Dunfa Peng, Nadeem Sidiq Bhat, Mohammed Soutto, EL-Rifai Wael, Zheng Chen. Overcoming MK1775 resistance in upper gastrointestinal cancers with combined WEE1 and CHK1 inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4744.

Nutrient Intakes and Gastrointestinal Symptoms Among Esophagogastric Cancer Survivors up to 5 Years Post-Surgery

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13–36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James’ Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.

Opinion, uptake and current practice of robot-assisted upper gastrointestinal and oesophagogastric surgery in the UK: AUGIS national survey results.

The uptake of upper gastrointestinal (GI) robotic surgery in the United Kingdom (UK), and Europe more widely, is expanding rapidly. This study aims to present a current snapshot of the practice and opinions of the upper GI community with reference to robotic surgery, with an emphasis on tertiary cancer (oesophagogastric) resection centres. An electronic survey was circulated to the UK upper GI surgical community via national mailing lists, social media and at an open-invitation conference on robotic upper GI surgery in January 2023. The survey included questions on surgeons' current practice or planned adoption (if any) of robotics at individual and unit level, and their opinions on robotic upper GI surgery in general. Priority ranking and Likert-scale response options were used. In total, 81 respondents from 43 hospitals were included. Thirty-four resectional centres responded, including 30 of 31 (97%) recognised upper GI cancer centres in England. Respondents reported performing robotic surgery in 21 of 34 (61.8%) resectional centres, with a median of 65 procedures per centre performed at the time of the survey (range 0-500, interquartile range 93.75). Every centre without a robotic programme expressed a desire or had active plans to implement one. Respondents ranked surgeon ergonomics as the most important reason for pursuing robotics, followed by improvements in patient outcomes and oncological efficacy. Robotic upper GI practice is nascent but rapidly growing in the UK with plans for uptake in almost all tertiary centres. There is growing opinion that this is likely to become the predominant surgical approach in future with benefits to both patients and surgeons. This snapshot offers a point of reference to all stakeholders in upper GI surgery.

Comprehensive evaluation of serum hepatic proteins in predicting prognosis among cancer patients with cachexia: an observational cohort study

BackgroundHepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia.MethodsThis multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan–Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL).ResultsC-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28–1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19–1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25–1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels.ConclusionLow albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.

Burden of upper gastrointestinal cancers in the east of Golestan province (Golestan cohort study).

Cancers, especially Upper Gastrointestinal Cancers (UGCs), pose a substantial burden on society, particularly in developing nations. Golestan province, Iran, is known for its high UGC rates globally. This study delves into the disease burden of UGCs in the eastern part of Golestan province. This study was conducted using the results of the Golestan cohort study. 2711 patients participating in this cohort, who visited Atrak Clinic during 2001-2020, participated in this study. After excluding patients with incomplete records, 2481 patients were included in the study. To compute the metrics of years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life years (DALY), we utilized the World Health Organization's standard life table, stratified by age and gender. The majority of UGC patients in our study were married (81.8%), had limited formal education (82.6%), and were predominantly male (61.1%). A substantial proportion resided in suburban areas (85.8%), and over half of the patients (52%) reported a history of drug addiction. The mean age at diagnosis for men was 65.76 years with a standard deviation of 11.34, while for women, it was 64.38 years with a standard deviation of 11.66. Regarding disease impact, YLL, YLD, and DALY for men were 21 240, 1956, and 23 196 (307.8 per 100 000), respectively. For women, these figures were 15 609 for YLL, 1367 for YLD, and 16 976 (223.1 per 100 000) for DALY. After the increasing trend of the burden of UGCs in Golestan province in the early years of the study, this rate has been decreasing in recent years. Effective strategies necessitate collaborative efforts across various sectors to alleviate this burden, focusing on preventive measures, timely diagnosis, and well-coordinated therapeutic interventions.