Trends in mortality from gastrointestinal, hepatic, and pancreatic cancers in the United States: A comprehensive analysis (1999-2020).

Background and Aim: This study investigates temporal trends in gastrointestinal cancer-related mortality in the United States between 1999 and 2020, focusing on differences by sex, age, and race. Methods: We investigated the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research multiple causes of death database (Years 1999-2020) for gastrointestinal cancer-related mortality with a focus on the underlying cause of death. Results: A total of 3 115 243 gastrointestinal cancer-related deaths occurred from 1999 to 2020. The overall age-adjusted mortality rate decreased from 46.7 per 100 000 in 1999 to 38.4 per 100 000 in 2020. The average annual percent change (AAPC) for the study period was -0.9% (95% CI: -1.0%, -0.9%, P < 0.001), with no significant difference in AAPC between the sexes but some difference between races and related to individual cancers. African Americans and Asian Americans, and Pacific Islanders experienced a greater decrease in mortality compared with Whites. Mortality rates for American Indian and Alaskan Native populations also decreased significantly from 1999 to 2020 (P < 0.001). There were significant declines in esophageal, stomach, colon, rectal, and gallbladder cancer-related mortality but increases in the small bowel, anal, pancreatic, and hepatic cancer-related mortality (P < 0.001), with variation across different sexes and racial groups. Conclusion: While overall gastrointestinal cancer-related mortality declined significantly in the United States from 1999 to 2020, mortality from some cancers increased. Furthermore, differences between sexes and racial groups underscore crucial differences in gastrointestinal cancer mortality, highlighting areas for future research.

Germline homozygosity and allelic imbalance of HLA-I are common in esophagogastric adenocarcinoma and impair the repertoire of immunogenic peptides.

BACKGROUND: The individual HLA-I genotype is associated with cancer, autoimmune diseases and infections. This study elucidates the role of germline homozygosity or allelic imbalance of HLA-I loci in esophago-gastric adenocarcinoma (EGA) and determines the resulting repertoires of potentially immunogenic peptides. METHODS: HLA genotypes and sequences of either (1) 10 relevant tumor-associated antigens (TAAs) or (2) patient-specific mutation-associated neoantigens (MANAs) were used to predict good-affinity binders using an in silico approach for MHC-binding (www.iedb.org). Imbalanced or lost expression of HLA-I-A/B/C alleles was analyzed by transcriptome sequencing. FluoroSpot assays and TCR sequencing were used to determine peptide-specific T-cell responses. RESULTS: We show that germline homozygosity of HLA-I genes is significantly enriched in EGA patients (n=80) compared with an HLA-matched reference cohort (n=7605). Whereas the overall mutational burden is similar, the repertoire of potentially immunogenic peptides derived from TAAs and MANAs was lower in homozygous patients. Promiscuity of peptides binding to different HLA-I molecules was low for most TAAs and MANAs and in silico modeling of the homozygous to a heterozygous HLA genotype revealed normalized peptide repertoires. Transcriptome sequencing showed imbalanced expression of HLA-I alleles in 75% of heterozygous patients. Out of these, 33% showed complete loss of heterozygosity, whereas 66% had altered expression of only one or two HLA-I molecules. In a FluoroSpot assay, we determined that peptide-specific T-cell responses against NY-ESO-1 are derived from multiple peptides, which often exclusively bind only one HLA-I allele. CONCLUSION: The high frequency of germline homozygosity in EGA patients suggests reduced cancer immunosurveillance leading to an increased cancer risk. Therapeutic targeting of allelic imbalance of HLA-I molecules should be considered in EGA.

Colonic Angiolipoma: A Rare Cause of Chronic Anemia and Rectal Bleeding.

Angiolipomas are rare, benign tumors characterized by a mixture of adipose tissue and blood vessels, distinguishing them from lipomas. This case involves a 52-year-old woman with no significant medical history who presented with generalized weakness, fatigue, and intermittent, painless rectal bleeding over six months, initially dismissed as hemorrhoidal. Despite exhibiting mild pallor and trace rectal bleeding upon examination, significant iron-deficiency anemia was diagnosed through laboratory tests. Incorporating colonoscopy and computed tomography, the diagnostic process identified a 2 cm submucosal lesion in the ascending colon, characterized as a well-defined, fat-density mass. Histopathological analysis following surgical resection confirmed the diagnosis of a colonic angiolipoma. The patient's recovery, marked by the resolution of symptoms and normalization of hemoglobin levels, underscores the effectiveness of surgical treatment. This case highlights the diagnostic challenges posed by colonic angiolipomas due to their nonspecific symptoms. It emphasizes the importance of considering such rare entities in the differential diagnosis of gastrointestinal symptoms. This approach facilitates prompt and appropriate treatment, enriching the limited literature and advocating for clinical vigilance and interdisciplinary diagnostic strategies.

A Case of Gastrointestinal Stromal Tumour (GIST) in the Duodenum in a Young Adult.

Gastrointestinal stromal tumours (GISTs) are rare gastrointestinal (GI) malignancies, but the most prevalent mesenchymal tumours of the GI tract arise from the interstitial cells of Cajal. They account for 1-3% of all GI malignancies, and only 3-5% of all cases of GIST are located at the duodenal. We present a case of a young adult who presented to the ED with symptoms of GI bleeding.

Müllerian-type carcinosarcoma arising in gastric endometriosis: Case report and review of the literature.

Although endometriosis is a common condition, both extrapelvic endometriosis and endometriosis associated malignancy (EAM) are rare. We describe the first reported case of a patient with Müllerian-type carcinosarcoma arising in gastric endometriosis.

Modified FOLFOX6 plus bevacizumab with and without nivolumab for first-line treatment of metastatic colorectal cancer: phase 2 results from the CheckMate 9X8 randomized clinical trial.

BACKGROUND: Standard first-line therapies for metastatic colorectal cancer (mCRC) include fluoropyrimidine-containing regimens with oxaliplatin and/or irinotecan and a biologic agent. Immunotherapy may enhance antitumor activity in combination with standard therapies in patients with mCRC. Here, we present phase 2 results of nivolumab plus standard-of-care therapy (SOC; 5-fluorouracil/leucovorin/oxaliplatin/bevacizumab) versus SOC in the first-line treatment of patients with mCRC (CheckMate 9X8). METHODS: CheckMate 9X8 was a multicenter, open-label, randomized, phase 2/3 trial. Eligible patients were at least 18 years of age with unresectable mCRC and no prior chemotherapy for metastatic disease. Patients were randomized 2:1 to receive nivolumab 240 mg plus SOC or SOC alone every 2 weeks. The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors V.1.1. Secondary endpoints included PFS by investigator assessment; objective response rate (ORR), disease control rate, duration of response, and time to response, all by BICR and investigator assessments; overall survival; and safety. Preplanned exploratory biomarker analyses were also performed. RESULTS: From February 2018 through April 2019, 310 patients were enrolled, of which 195 patients were randomized to nivolumab plus SOC (n=127) or SOC (n=68). At 21.5-month minimum follow-up, PFS with nivolumab plus SOC versus SOC did not meet the prespecified threshold for statistical significance; median PFS by BICR was 11.9 months in both arms (HR, 0.81 (95% CI, 0.53 to 1.23); p=0.30). Higher PFS rates after 12 months (18 months: 28% vs 9%), higher ORR (60% vs 46%), and durable responses (median 12.9 vs 9.3 months) were observed with nivolumab plus SOC versus SOC. Grade 3-4 treatment-related adverse events were reported in 75% versus 48% of patients; no new safety signals were identified. CONCLUSIONS: The CheckMate 9X8 trial investigating first-line nivolumab plus SOC versus SOC in patients with mCRC did not meet its primary endpoint of PFS by BICR. Nivolumab plus SOC showed numerically higher PFS rates after 12 months, a higher response rate, and more durable responses compared with SOC alone, with acceptable safety. Further investigation to identify subgroups of patients with mCRC that may benefit from nivolumab plus SOC versus SOC in the first-line setting is warranted. TRIAL REGISTRATION NUMBER: NCT03414983.

Clinicopathological characterisation of MTAP alterations in gastrointestinal cancers.

BACKGROUND: Methylthioadenosine phosphorylase (MTAP) is an essential metabolic enzyme in the purine and methionine salvage pathway. In cancer, MTAP gene copy number loss (MTAP loss) confers a selective dependency on the related protein arginine methyltransferase 5. The impact of MTAP alterations in gastrointestinal (GI) cancers remains unknown although hypothetically druggable. Here, we aim to investigate the prevalence, clinicopathological features and prognosis of MTAP loss GI cancers. METHODS: Cases with MTAP alterations were retrieved from The Cancer Genome Atlas (TCGA) and a real-world cohort of GI cancers profiled by next-generation sequencing. If MTAP alterations other than loss were found, immunohistochemistry was performed. Finally, we set a case-control study to assess MTAP loss prognostic impact. RESULTS: Findings across the TCGA dataset (N=1363 patients) and our cohort (N=508) were consistent. Gene loss was the most common MTAP alteration (9.4%), mostly co-occurring with CDKN2A/B loss (97.7%). Biliopancreatic and gastro-oesophageal cancers had the highest prevalence of MTAP loss (20.5% and 12.7%, respectively), being mostly microsatellite stable (99.2%). In colorectal cancer, MTAP loss was rare (1.1%), while most MTAP alterations were mutations (5/7, 71.4%); among the latter, only MTAP-CDKN2B truncation led to protein loss, thus potentially actionable. MTAP loss did not confer worse prognosis. CONCLUSIONS: MTAP alterations are found in 5%-10% of GI cancers, most frequently biliopancreatic and gastro-oesophageal. MTAP loss is the most common alteration, identified almost exclusively in MSS, CDKN2A/B loss, upper-GI cancers. Other MTAP alterations were found in colorectal cancer, but unlikely to cause protein loss and drug susceptibility.

Metastatic gastric cancer target lesion complete response with Claudin18.2-CAR T cells.

Treatment of hematologic malignancies with patient-derived anti-CD19 chimeric antigen receptor (CAR) T-cells has demonstrated long-term remissions for patients with otherwise treatment-refractory advanced leukemia and lymphoma. Conversely, CAR T-cell treatment of solid tumors, including advanced gastric cancer (GC), has proven more challenging due to on-target off-tumor toxicities, poor tumor T-cell infiltration, inefficient CAR T-cell expansion, immunosuppressive tumor microenvironments, and demanding preconditioning regimens. We report the exceptional results of autologous Claudin18.2-targeted CAR T cells (CT041) in a patient with metastatic GC, who had progressed on four lines of combined systemic chemotherapy and immunotherapy. After two CT041 infusions, the patient had target lesion complete response and sustained an 8-month overall partial response with only minimal ascites. Moreover, tumor-informed circulating tumor DNA (ctDNA) reductions coincided with rapid CAR T-cell expansion and radiologic response. No severe toxicities occurred, and the patient's quality of life significantly improved. This experience supports targeting Claudin18.2-positive GC with CAR T-cell therapy and helps to validate ctDNA as a biomarker in CAR T-cell therapy. Clinical Insight: Claudin18.2-targeted CAR T cells can safely provide complete objective and ctDNA response in salvage metastatic GC.

Multiomic molecular characterization of the response to combination immunotherapy in MSS/pMMR metastatic colorectal cancer.

BACKGROUND: Immune checkpoint inhibitor (ICI) combinations represent an emerging treatment strategies in cancer. However, their efficacy in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer (CRC) is variable. Here, a multiomic characterization was performed to identify predictive biomarkers associated with patient response to ICI combinations in MSS/pMMR CRC for the further development of ICI combinations. METHODS: Whole-exome sequencing, RNA sequencing, and multiplex fluorescence immunohistochemistry of tumors from patients with MSS/pMMR CRC, who received regorafenib plus nivolumab (REGONIVO) or TAS-116 plus nivolumab (TASNIVO) in clinical trials were conducted. Twenty-two and 23 patients without prior ICI from the REGONIVO and TASNIVO trials were included in this study. A biomarker analysis was performed using samples from each of these studies. RESULTS: The epithelial-mesenchymal transition pathway and genes related to cancer-associated fibroblasts were upregulated in the REGONIVO responder group, and the G2M checkpoint pathway was upregulated in the TASNIVO responder group. The MYC pathway was upregulated in the REGONIVO non-responder group. Consensus molecular subtype 4 was significantly associated with response (p=0.035) and longer progression-free survival (p=0.006) in the REGONIVO trial. CD8+ T cells, regulatory T cells, and M2 macrophages density was significantly higher in the REGONIVO trial responders than in non-responders. Mutations in the POLE gene and patient response were significantly associated in the TASNIVO trial; however, the frequencies of other mutations or tumor mutational burden were not significantly different between responders and non-responders in either trial. CONCLUSIONS: We identified molecular features associated with the response to the REGONIVO and TASNIVO, particularly those related to tumor microenvironmental factors. These findings are likely to contribute to the development of biomarkers to predict treatment efficacy for MSS/pMMR CRC and future immunotherapy combinations for treatment.

Essentials of macroscopic evaluation of specimens from gastrointestinal tract.

An astute macroscopic examination, coupled with correlating the gross findings with clinical indication and operative notes along with judicious, yet all pertinent sectioning for pathological examination is crucial for an accurate histopathological diagnosis, eventually leading to optimal patient care. This succinct review highlights the general concepts that lay the foundation of evaluating and grossing specimens from the luminal gastrointestinal (GI) tract. We also discuss the gross evaluation and sectioning of small therapeutic resections, along with a systematic approach and rationale when grossing and submitting histological sections from larger oncological resections from the luminal GI tract. Selected site-specific considerations, for example, grossing treated rectal and oesophageal cancers or taking sections from mucinous tumours of the appendix, among others, are also discussed.

VB-111 (ofranergene obadenovec) in combination with nivolumab in patients with microsatellite stable colorectal liver metastases: a single center, single arm, phase II trial.

BACKGROUND: Microsatellite stable colorectal liver metastases (MSS CLM) maintain an immunosuppressive tumor microenvironment (TME). Historically, immune-based approaches have been ineffective. VB-111 (ofranergene obadenovec) is a genetically-modified adenoviral vector targeting the TME; its unique dual mechanism induces an immune response and disrupts neovascularization. Checkpoint inhibition may synergize the immune response induced by viral-mediated anti-angiogenic gene therapy. We aimed to examine the safety and antitumor activity of VB-111 and nivolumab in patients with refractory MSS CLM and to characterize immunological treatment-response. METHODS: This was a phase II study of adult patients with histologically-confirmed MSS CLM who progressed on prior therapy. A priming dose of VB-111 1×1013 viral particles was given intravenously 2 weeks prior to starting biweekly nivolumab 240 mg and continued every 6 weeks. The combination continued until disease progression or unacceptable toxicity. The primary objectives were overall response rate and safety/tolerability. Secondary objectives included median overall survival and progression-free survival. Correlative studies were performed on paired tumor biopsies and blood. RESULTS: Between August 2020 and December 2021, 14 patients were enrolled with median age 50.5 years (40-75), and 14% were women. Median follow-up was 5.5 months. Of the 10 evaluable patients, the combination of VB-111 and nivolumab failed to demonstrate radiographic responses; at best, 2 patients had stable disease. Median overall survival was 5.5 months (95% CI: 2.3 to 10.8), and median progression-free survival was 1.8 months (95% CI: 1.4 to 1.9). The most common grade 3-4 treatment-related adverse events were fever/chills, influenza-like symptoms, and lymphopenia. No treatment-related deaths were reported. Qualitative analysis of immunohistochemical staining of paired tumor biopsies did not demonstrate significant immune infiltration after treatment, except for one patient who had exceptional survival (26.0 months). Immune analysis of peripheral blood mononuclear cells showed an increase of PD-1highKi67highCD8+ T cells and HLA-DRhigh T cells after VB-111 priming dose. Plasma cytokines interleukin-10 and tumor necrosis factor-α increased after treatment with both drugs. CONCLUSION: In patients with MSS CLM, VB-111 and nivolumab did not improve overall response rate or survival but were tolerated with minimal toxicities. While challenging to distinguish between antiviral or antitumor, correlative studies demonstrated an immune response with activation and proliferation of CD8+ T cells systemically that was poorly sustained. TRIAL REGISTRATION NUMBER: NCT04166383.

CCR5 and CCL5 gene expression in colorectal cancer: comprehensive profiling and clinical value.

BACKGROUND: The C-C motif chemokine receptor 5 (CCR5)/C-C motif chemokine ligand 5 (CCL5) axis plays a major role in colorectal cancer (CRC). We aimed to characterize the molecular features associated with CCR5/CCL5 expression in CRC and to determine whether CCR5/CCL5 levels could impact treatment outcomes. METHODS: 7604 CRCs tested with NextGen Sequencing on DNA and RNA were analyzed. Molecular features were evaluated according to CCR5 and CCL5 tumor gene expression quartiles. The impact on treatment outcomes was assessed in two cohorts, including 6341 real-world patients and 429 patients from the Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial. RESULTS: CCR5/CCL5 expression was higher in right-sided versus left-sided tumors, and positively associated with consensus molecular subtypes 1 and 4. Higher CCR5/CCL5 expression was associated with higher tumor mutational burden, deficiency in mismatch repair and programmed cell death ligand 1 (PD-L1) levels. Additionally, high CCR5/CCL5 were associated with higher immune cell infiltration in the tumor microenvironment (TME) of MMR proficient tumors. Ingenuity pathway analysis revealed upregulation of the programmed cell death protein 1 (PD-1)/PD-L1 cancer immunotherapy pathway, phosphatase and tensin homolog (PTEN) and peroxisome proliferator-activated receptors (PPAR) signaling, and cytotoxic T-lymphocyte antigen 4 (CTLA-4) signaling in cytotoxic T lymphocytes, whereas several inflammation-related pathways were downregulated. Low CCR5/CCL5 expression was associated with increased benefit from cetuximab-FOLFOX treatment in the CALGB/SWOG 80405 trial, where significant treatment interaction was observed with biologic agents and chemotherapy backbone. CONCLUSIONS: Our data show a strong association between CCR5/CCL5 gene expression and distinct molecular features, gene expression profiles, TME cell infiltration, and treatment benefit in CRC. Targeting the CCR5/CCL5 axis may have clinical applications in selected CRC subgroups and may play a key role in developing and deploying strategies to modulate the immune TME for CRC treatment.

Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders.

BACKGROUND: Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed. METHODS: This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18). RESULTS: In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder's TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response. CONCLUSIONS: Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab.

The association between objectively measured preoperative light-intensity physical activity and postoperative ambulation in patients with gastrointestinal cancer.

[Purpose] To clarify the association between preoperative physical activity and postoperative ambulation based on physical activity intensity, and independent of functional capacity and depression, in patients with gastrointestinal cancer. [Participants and Methods] Seventy patients who underwent surgery for primary colorectal or gastric cancer were enrolled. Preoperative moderate-to-vigorous-intensity physical activity, light-intensity physical activity, and sedentary behavior were assessed using an accelerometer. The primary outcome was the days to postoperative first ambulation (capable of independently and continuously walking 150 m). Functional capacity and depression, as confounders, were evaluated by measuring the 6-minute walk distance and using the Hospital Anxiety and Depression Scale. [Results] Of the 70 patients, 28 had insufficient accelerometer data, and 42 were included in the analysis. Preoperative light-intensity physical activity, but not moderate-to-vigorous-intensity physical activity and sedentary behavior, was negatively associated with the days to postoperative first ambulation, after adjusting for age, preoperative functional capacity, and preoperative depression. [Conclusion] Preoperative light-intensity physical activity was associated with the days to postoperative ambulation independently of age, functional capacity, and depression. Hence, predicting delayed ambulation by preoperative light-intensity physical activity in patients with gastrointestinal cancer may be useful.

Combined Lanreotide Autogel and Temozolomide Treatment of Progressive Pancreatic and Intestinal Neuroendocrine Tumors: The Phase II SONNET Study.

BACKGROUND: In advanced neuroendocrine tumors (NET), antiproliferative treatment options beyond somatostatin analogs remain limited. Temozolomide (TMZ) has shown efficacy in NET alone or combined with other drugs. MATERIALS AND METHODS: SONNET (NCT02231762) was an open, multicenter, prospective, phase II study to evaluate lanreotide autogel 120 mg (LAN) plus TMZ in patients with progressive advanced/metastatic grade 1/2 gastroenteropancreatic (GEP) NET or of unknown primary. Patients could be enrolled at first-line or higher therapy line. The primary endpoint was disease control rate ([DCR], rate of stable disease [SD], partial [PR], and complete response [CR]) at 6 months of LAN and TMZ. Patients with nonfunctioning (NF) NET without progression at 6 months were randomized to 6-month LAN maintenance or watch and wait, patients with functioning (F)-NET with clinical benefit (PR, SD) continued on LAN. RESULTS: Fifty-seven patients were recruited. The majority of patients received the study drug at second or higher treatment line and had an NET G2. DCR at 6 months LAN and TMZ was 73.5%. After 6 months of further LAN maintenance, 54.5% of patients with F-NET and 71.4% with NF-NET had SD or PR vs 41.7% with NF-NET on observation only. LAN and TMZ were effective in all subgroups analyzed. At 12 months of follow-up, median progression-free survival was 11.1 months. Median serum chromogranin A decreased except in NF-NET on observation. O6-methylguanine DNA methyltransferase promoter methylation appeared to better reflect TMZ response than loss of gene expression. During combination therapy, the most frequent treatment-emergent adverse events grade 3/4 reported were nausea (14%), thrombocytopenia (12.3%), and neutropenia (8.8%). Four deaths were reported resulting from severe adverse events not considered related to study medication. CONCLUSIONS: LAN plus TMZ is a treatment option for patients with progressive GEP-NET with more aggressive biological profile showing a manageable safety profile.

Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study.

BACKGROUND: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.

Preoperative 6-minute walk distance is associated with postoperative complications in patients undergoing laparoscopic gastrointestinal cancer surgery.

OBJECTIVE: The 6-min walk test (6MWT) is a simple and valid method to evaluate cardiopulmonary function. We performed this prospective study in patients undergoing laparoscopic gastrointestinal cancer surgery to explore the association between preoperative 6MWT performance and overall postoperative complications. METHODS: This study was registered at clinicaltrials.gov (NCT03711526). The study consecutively enrolled patients receiving laparoscopic gastrointestinal cancer surgery in our institution. All patients performed the 6MWT upon recruitment and received 30 days of postoperative follow-up. The primary outcome was overall complications, defined by ≥ grade I Clavien-Dindo (CD) classification (2004) complications. Multivariable logistic regression was used to test the association of 6-min walk distance (6MWD) with the outcome. RESULTS: A total of 184 patients were included in the final analyses. In the 37 (20.1 %) patients with overall complications, the mean (standard deviation) preoperative 6MWD was 469.1 (86.8) m. In patients with no complications, the 6MWD was 502.6 (90.2) m. The mean difference was 33.5 m (95 % confidence interval, 1.3, 65.7; P = 0.042). A longer preoperative 6MWD was associated with a lower odds of developing postoperative complications (odds ratio, 0.994 per meter increase; 95 % confidence interval, 0.989, 0.999; p = 0.023). CONCLUSION: This study indicated an association between the preoperative 6MWD and postoperative complications in patients undergoing laparoscopic gastrointestinal cancer surgery.

Association between Metabolically Healthy Status and Risk of Gastrointestinal Cancer.

PURPOSE: Although obesity is associated with numerous diseases, the risks of disease may depend on metabolically healthy status. Nevertheless, it is unclear to whether metabolically healthy status affects risk of gastrointestinal (GI) cancer in general Chinese population. MATERIALS AND METHODS: A total of 114,995 participants who met the criteria were included from the Kailuan Study. The study participants were divided into four groups according to body mass index (BMI)/waist circumference (WC) and metabolic status. Incident of GI cancer (esophageal cancer, gastric cancer, liver cancer, biliary cancer, pancreatic cancer, and colorectal cancer) during 2006-2020 were confirmed by review of medical records. The Cox proportional hazard regression models were used to assess the association metabolically healthy status with the risk of GI cancer by calculating the hazard ratios (HR) and 95% confidence interval (CI). RESULTS: During a mean 13.76 years of follow-up, we documented 2,311 GI cancers. Multivariate Cox regression analysis showed that compared with the metabolically healthy normal-weight group, metabolically healthy obese (MHO) participants demonstrated an increased risk of developing GI cancer (HR, 1.54; 95% CI, 1.11 to 2.13) by BMI categories. However, such associations were not found for WC category. These associations were moderated by age, sex, and anatomical site of the tumor. Individuals with metabolic unhealthy normal-weight or metabolic unhealthy obesity phenotype also have an increased risk of GI cancer. CONCLUSION: MHO phenotype was associated with increased risk of GI cancer. Moreover, individuals who complicated by metabolic unhealthy status have an increased risk of developing GI cancer. Hence, clinicians should consider the risk of incident GI cancer in people with abnormal metabolically healthy status and counsel them about metabolic fitness and weight control.

An acute care surgeon's dilemma: Operative vs. non-operative management of emergency general surgery conditions in patients with recent colorectal cancer treatment.

BACKGROUND: This comparative effectiveness study examined outcomes of operative vs. non-operative management for emergency general surgery (EGS) conditions in patients with recent cancer treatment (RT). METHODS: Medicare beneficiaries with a history of colorectal cancer hospitalized for an EGS condition (2016-2018) were identified. RT was defined as chemotherapy/radiation within 3 months prior to admission. Instrumental variable analysis assessed the impact of management on mortality and readmissions among survivors (30d, 60d, and 90d), for patients in whom there was clinical equipoise regarding optimal management strategy. RESULTS: Of 26,097 patients, 13% had undergone RT. In both the RT and non-RT groups, the optimal management strategy was uncertain in 14%. Operative management conferred increased risk of mortality but not readmission in patients with RT compared to those without (90d mortality:+43%, p â€‹= â€‹0.03; 90d readmission:+7.1%, p â€‹= â€‹0.776). CONCLUSIONS: In patients with RT for whom there is clinical equipoise regarding EGS management, operative intervention increases risk of mortality.

Macroscopic pathology and all that: a personal view.

I hope that this treatise adds to the excellent reviews by Varma and colleagues, emphasising the importance of accurate macroscopic assessment and report provision. I have especially highlighted the importance of not divorcing the clinical data and the macroscopic analysis from the microscopic assessment as all are required to provide an accurate and cogent overall composition. The review has also identified areas where the evolution of pathological practice has gone a little awry and requires to be modified and/or justified with evidence base. There is also an emphasis on block economy, as there is no doubt that considerable savings can be made if more attention is paid to more judicious block selection. It is also commended that subspecialties other than gastrointestinal pathology introduce reporting quality standards, like lymph node harvest numbers and other important prognostic and management indicators, to improve the quality of macroscopic pathology worldwide to the benefit of our service users and their patients.