Exploratory investigation of virtual lesions in gastrointestinal endoscopy using a novel phase-shift method for three-dimensional shape measurement.

Accurate measurement of the size of lesions or distances between any two points during endoscopic examination of the gastrointestinal tract is difficult owing to the fisheye lens used in endoscopy. To overcome this issue, we developed a phase-shift method to measure three-dimensional (3D) data on a curved surface, which we present herein. Our system allows the creation of 3D shapes on a curved surface by the phase-shift method using a stripe pattern projected from a small projecting device to an object. For evaluation, 88 measurement points were inserted in porcine stomach tissue, attached to a half-pipe jig, with an inner radius of 21 mm. The accuracy and precision of the measurement data for our shape measurement system were compared with the data obtained using an Olympus STM6 measurement microscope. The accuracy of the path length of a simulated protruded lesion was evaluated using a plaster model of the curved stomach and graph paper. The difference in height measures between the measurement microscope and measurement system data was 0.24 mm for the 88 measurement points on the curved surface of the porcine stomach. The error in the path length measurement for a lesion on an underlying curved surface was <1% for a 10-mm lesion. The software was developed for the automated calculation of the major and minor diameters of each lesion. The accuracy of our measurement system could improve the accuracy of determining the size of lesions, whether protruded or depressed, regardless of the curvature of the underlying surface.

Palliative care case management in a surgical department for patients with gastrointestinal cancer-a register-based cohort study.

BACKGROUND: The effectiveness of generalist palliative care interventions in hospitals is unknown. AIM: This study aimed to explore the impact of a palliative care case management intervention for patients with gastrointestinal cancer (PalMaGiC) on hospital admissions, healthcare use, and place of death. DESIGN: This was a register-based cohort study analyzing data from the Danish Register on Causes of Death, the Danish National Patient Register, and the Danish Palliative Database. SETTING/PARTICIPANTS: Deceased patients with gastrointestinal cancer from 2010 to 2020 exposed to PalMaGiC were compared over three periods of time to patients receiving standard care. RESULTS: A total of 43,969 patients with gastrointestinal cancers were included in the study, of whom 1518 were exposed to PalMaGiC. In the last 30 days of life, exposed patients were significantly more likely to be hospitalized (OR of 1.62 (95% CI 1.26-2.01)), spend more days at the hospital, estimate of 1.21 (95% CI 1.02-1.44), and have a higher number of hospital admissions (RR of 1.13 (95% CI 1.01-1.27)), and were more likely to die at the hospital (OR of 1.94 (95% CI 1.55-2.44)) with an increasing trend over time. No differences were found for hospital healthcare use. CONCLUSION: Patients exposed to the PalMaGiC intervention had a greater likelihood of hospitalizations and death at the hospital compared to unexposed patients, despite the opposite intention. Sensitivity analyses show that regional differences may hold some of the explanation for this. Future development of generalist palliative care in hospitals should focus on integrating a home-based approach, community care, and PC physician involvement.

Experiences of informal caregivers supporting individuals with upper gastrointestinal cancers: a systematic review.

BACKGROUND: Upper gastrointestinal cancers (UGICs) are increasingly prevalent. With a poor prognosis and significant longer-term effects, UGICs present significant adjustment challenges for individuals with cancer and their informal caregivers. However, the supportive care needs of these informal caregivers are largely unknown. This systematic review of qualitative studies synthesises and critically evaluates the current evidence base on the experience of informal caregivers of individuals with UGIC. METHODS: A Joanna Briggs Institute systematic review was conducted. Searches were performed in four databases (MEDLINE, PsycINFO, Embase, CINAHL) from database inception to February 2021. Included studies explored experiences of informal caregivers of individuals diagnosed with primary cancer of the oesophagus, stomach, pancreas, bile duct, gallbladder, or liver. Studies were independently screened for eligibility and included studies were appraised for quality by two reviewers. Data were extracted and synthesised using meta-aggregation. RESULTS: 19 papers were included in this review, and 328 findings were extracted. These were aggregated into 16 categories across three findings: (1) UGIC caregiver burden; UGIC caregivers undertake extensive responsibilities, especially around patient diet as digestion is severely impacted by UGICs. (2) Mediators of caregiver burden; The nature of UGICs, characterised by disruptive life changes for caregivers, was identified as a mediator for caregiver burden. (3) Consequences of caregiver burden: UGIC caregivers' experiences were shaped by unmet needs, a lack of information and a general decline in social interaction. CONCLUSIONS: The findings of this review suggest the need for a cultural shift within health services. Caregiving for UGIC patients is suggested to adversely affect caregivers' quality of life, similarly to other cancer caregiving populations and therefore they should be better incorporated as co-clients in care-planning and execution by including them in discussions about the patient's diagnosis, treatment options, and potential side effects.

Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma represents one of the solid tumors showing the worst prognosis worldwide, with a high recurrence rate after adjuvant or neoadjuvant therapy. Circulating tumor DNA analysis raised as a promising non-invasive tool to characterize tumor genomics and to assess treatment response. In this study, surgical tumor tissue and sequential blood samples were analyzed by next-generation sequencing and were correlated with clinical and pathological characteristics. Thirty resectable/borderline pancreatic ductal adenocarcinoma patients treated at the Hospital Universitario de Navarra were included. Circulating tumoral DNA sequencing identified pathogenic variants in KRAS and TP53, and in other cancer-associated genes. Pathogenic variants at diagnosis were detected in patients with a poorer outcome, and were correlated with response to neoadjuvant therapy in borderline pancreatic ductal adneocarcinoma patients. Higher variant allele frequency at diagnosis was associated with worse prognosis, and thesum of variant allele frequency was greater in samples at progression. Our results build on the potential value of circulating tumor DNA for non-metastatic pancreatic ductal adenocarcinoma patients, by complementing tissue genetic information and as a non-invasive tool for treatment decision. Confirmatory studies are needed to corroborate these findings.

Update in the management of gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine neoplasms are a diverse group of neoplasms that can occur in various areas throughout the body. Well-differentiated neuroendocrine tumors (NETs) most often arise in the gastrointestinal tract, termed gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Although GEP-NETs are still uncommon, their incidence and prevalence have been steadily increasing over the past decades. The primary treatment for GEP-NETs is surgery, which offers the best chance for a cure. However, because GEP-NETs are often slow-growing and do not cause symptoms until they have spread widely, curative surgery is not always an option. Significant advances have been made in systemic and locoregional treatment options in recent years, including peptide-receptor radionuclide therapy with α and ß emitters, somatostatin analogs, chemotherapy, and targeted molecular therapies.

Trends and hotspots in gastrointestinal neoplasms risk assessment: A bibliometric analysis from 1984 to 2022.

BACKGROUND: Gastrointestinal neoplasm (GN) significantly impact the global cancer burden and mortality, necessitating early detection and treatment. Understanding the evolution and current state of research in this field is vital. AIM: To conducts a comprehensive bibliometric analysis of publications from 1984 to 2022 to elucidate the trends and hotspots in the GN risk assessment research, focusing on key contributors, institutions, and thematic evolution. METHODS: This study conducted a bibliometric analysis of data from the Web of Science Core Collection database using the "bibliometrix" R package, VOSviewer, and CiteSpace. The analysis focused on the distribution of publications, contributions by institutions and countries, and trends in keywords. The methods included data synthesis, network analysis, and visualization of international collaboration networks. RESULTS: This analysis of 1371 articles on GN risk assessment revealed a notable evolution in terms of research focus and collaboration. It highlights the United States' critical role in advancing this field, with significant contributions from institutions such as Brigham and Women's Hospital and the National Cancer Institute. The last five years, substantial advancements have been made, representing nearly 45% of the examined literature. Publication rates have dramatically increased, from 20 articles in 2002 to 112 in 2022, reflecting intensified research efforts. This study underscores a growing trend toward interdisciplinary and international collaboration, with the Journal of Clinical Oncology standing out as a key publication outlet. This shift toward more comprehensive and collaborative research methods marks a significant step in addressing GN risks. CONCLUSION: This study underscores advancements in GN risk assessment through genetic analyses and machine learning and reveals significant geographical disparities in research emphasis. This calls for enhanced global collaboration and integration of artificial intelligence to improve cancer prevention and treatment accuracy, ultimately enhancing worldwide patient care.

Hepatocellular carcinoma: An analysis of the expression status of stress granules and their prognostic value.

BACKGROUND: Hepatocellular carcinoma (HCC) is a global popular malignant tumor, which is difficult to cure, and the current treatment is limited. AIM: To analyze the impacts of stress granule (SG) genes on overall survival (OS), survival time, and prognosis in HCC. METHODS: The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC), GSE25097, and GSE36376 datasets were utilized to obtain genetic and clinical information. Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach, and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression, respectively. The prognostic model's receiver operating characteristic (ROC) curve was produced and plotted utilizing the time ROC software package. Nomogram models were constructed to predict the outcomes at 1, 3, and 5-year OS prognostications with good prediction accuracy. RESULTS: We identified seven SG genes (DDX1, DKC1, BICC1, HNRNPUL1, CNOT6, DYRK3, CCDC124) having a prognostic significance and developed a risk score model. The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group (P < 0.001). The nomogram model's findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort. Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle, RNA editing, and other biological processes. CONCLUSION: Based on the impact of SG genes on HCC prognosis, in the future, it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations.

Background: In Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients < 50 years old compared to Western populations, possibly due to a higher frequency of Lynch syndrome (LS) in CRC patients. We aimed to examine the association of KRAS and PIK3CA mutations with LS. Methods: In this retrospective cross-sectional single-center study, the PCR-HRM-based test was used for screening of microsatellite instability (MSI) mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF (V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples. Results: All the samples (n = 244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples, respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples, respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples, respectively. PIK3CA mutation was significantly associated with female sex and lower levels of tumor-infiltrating lymphocytes in 62/107 (57.94%) and 26/107 (30.23%) samples, respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients. Conclusions: The high probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations.

Molecular profiling of visible polypoid and invisible conventional intestinal-type low-grade dysplasia in patients with idiopathic inflammatory bowel disease.

AIMS: Little is known about the molecular features of visible polyps with low-grade intestinal-type dysplasia in patients with inflammatory bowel disease (IBD). To better understand their origins and biological potential, we sought to genomically profile these lesions and compare them with invisible low-grade dysplasia and sporadic adenomas from non-IBD patients. METHODS: 22 polyps within areas of colitis, 13 polyps outside areas of colitis, 10 foci of invisible dysplasia from patients with IBD and 6 sporadic tubular adenomas from non-IBD patients were analysed using the OncoPanel assay. RESULTS: Polyps arising in areas of colitis showed a greater spectrum of mutations, including APC, KRAS, FBXW7, TP53, ARID1A and TCF7L2. Polyps outside colitis and non-IBD sporadic adenomas showed a limited mutational profile, with APC and CTNNB1 mutations. Invisible dysplasia was characterised by TP53, CTNNB1 and KRAS alterations. Compared with dysplastic polyps, none of the invisible dysplastic foci showed APC alterations (73%-within colitis; p=0.0001, 92%-outside colitis; p<0.0001, 83%-sporadic adenomas; p=0.001). TP53 mutations were significantly higher in invisible dysplasia (50%) compared with polyps within colitis (9%; p=0.02) and outside colitis (8%; p=0.03). CONCLUSIONS: Molecular alterations in visible low-grade dysplastic polyps with conventional intestinal-type dysplasia from patients with IBD and sporadic adenomas from non-IBD patients overlap significantly. APC alterations appear to play a major role in the development of visible low-grade dysplastic lesions in patients with IBD, regardless of background colitis. As with IBD-associated colorectal cancers, TP53 mutations are an early event in the development of invisible, low-grade conventional intestinal-type dysplasia in patients with IBD.

Immunotherapy in the neoadjuvant treatment of gastrointestinal tumors: is the time ripe?

Immune checkpoint inhibitors (ICIs) revolutionized the management of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal (GI) cancers. Based on notable results observed in the metastatic setting, several clinical trials investigated ICIs as neoadjuvant treatment (NAT) for localized dMMR/MSI-H GI cancers, achieving striking results in terms of clinical and pathological responses and creating the opportunity to spare patients from neoadjuvant chemotherapy and/or radiotherapy and even surgical resection. Nevertheless, these impressive findings are mainly derived from small proof of concept phase II studies and there are still several open questions to address. Moreover, dMMR/MSI-H represents a limited subgroup accounting for less than 10% of GI cancers. Consequently, many efforts have been produced to investigate neoadjuvant ICIs also in mismatch repair-proficient/microsatellite stable (MSS) cancers, considering the potential synergistic effect in combining immune-targeted agents with standard therapies such as chemo and/or radiotherapy. However, results for combining ICIs to the standard of care in the unselected population are still unsatisfactory, without improvements in event-free survival in esophago-gastric adenocarcinoma for the addition of pembrolizumab to chemotherapy, and sometimes limited benefit in patients with locally advanced rectal cancer. Therefore, a major challenge will be to identify among the heterogenous spectrum of this disease, those patients that could take advantage of neoadjuvant immunotherapy and deliver the most effective treatment. In this review we discuss the rationale of NAT in GI malignancies, summarize the available evidence regarding the completed trials that evaluated this treatment strategy in both MSI-H and MSS tumors. Finally, we discuss ongoing studies and future perspectives to render neoadjuvant immunotherapy another arrow in the quiver for the treatment of locally advanced GI tumors.

The psychological distress of gastrointestinal cancer patients and its association with quality of life among different genders.

BACKGROUND: Psychological distress is a prevalent unpleasant experience faced by many cancer patients. However, the psychological distress among gastrointestinal (GI) cancer patients is scarcely explored. Moreover, the association between psychological distress and quality of life in different genders has yet to be explored. AIMS: To explore the psychological distress among GI cancer patients and examine its association with quality of life among different genders. METHODS: This study was a cross-sectional study. A total of 237 gastrointestinal cancer patients completed the distress thermometer and the Functional Assessment of Chronic Illness Therapy-General. RESULTS: The mean score of psychological distress of the participants was 3.04 (SD = 2.90). A greater proportion of female gastrointestinal cancer patients (52.8%) had clinically relevant psychological distress compared to males (35.9%). The quality of life was negatively associated with their psychological distress (B = - 1.502, 95%CI: - 2.759 to - 0.245, p = 0.019) among gastrointestinal cancer patients. Such association was stronger among males compared to females in gastrointestinal cancer patients (Interaction term, B = - 1.713, 95%CI: - 3.123 to - 0.303, p = 0.017). CONCLUSIONS: These findings suggest that healthcare providers should attach their attention to gastrointestinal cancer patients' psychological distress, especially females. Longitudinal studies could adopted to track the changes in psychological distress and its association with quality of life over time among different genders. In future intervention studies, the focus of psychological interventions needs to be gender-specific.

Nutritional Prognosis of Patients Submitted to Radiotherapy and Its Implications in Treatment.

Oncological patients show intense catabolic activity, as well as a susceptibility to higher nutritional risk and clinical complications. Thus, tools are used for monitoring prognosis. Our objective was to analyze the nutrition prognosis of patients who underwent radiotherapy, correlating it with outcomes and complications. We performed a retrospective transversal study based on secondary data from hospital records of patients who started radiotherapy between July 2022 and July 2023. We established Prognostic Scores through a combination of Prognostic Nutritional Index (PNI) and a Subjective Global Assessment (SGA), assessed at the beginning and end of treatment. Score 3 patients, with PNI ≤ 45.56 and an SGA outcome of malnutrition, initially presented a higher occurrence of odynophagia, later also being indicative of reduced diet volume, treatment interruption, and dysphagia. SGA alone showed sensitivity to altered diet volume, dysphagia, and xerostomia in the second assessment. Besides this, PNI ≤ 45.56 also indicated the use of alternative feeding routes, treatment interruption, and hospital discharge with more complications. We conclude that the scores could be used to indicate complications; however, further studies on combined biomarkers are necessary.

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.

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.

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.

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.