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We aimed to determine the impact of fibroblast activation protein inhibitor (FAPI)-directed molecular imaging on staging and therapeutic management in patients affected with digestive system tumors when compared with guideline-compatible imaging (GCI).Thirty-two patients with tumors of the digestive system were included: colon adenocarcinoma, 2/32 (6.3%); hepatocellular carcinoma (HCC), 6/32 (18.8%); pancreatic duct adenocarcinoma (PDAC), 6/32 (18.8%), and gastroenteropancreatic neuroendocrine neoplasms, 18/32 (56.3%). All patients underwent GCI and 68 Ga-FAPI-04 PET/CT within median 4 days. Staging outcomes and subsequent treatment decisions were compared between GCI and 68 Ga-FAPI-04 PET/CT.Compared with GCI, 68 Ga-FAPI-04 PET/CT led to staging changes in 15/32 patients (46.9%). Among those, downstaging was recorded in 3/15 cases (20.0%) and upstaging in the remaining 12/15 patients (HCC, 4/12 [33.3%]; PDAC, 4/12 [33.3%]; neuroendocrine neoplasms, 3/12 [25%]; colon adenocarcinoma, 1/12 [8.3%]). Therapeutic management was impacted in 8/32 patients (25.0%), including 4 instances of major and 4 instances of minor therapeutic changes. The highest proportion of treatment modifications was observed in patients diagnosed with PDAC and HCC in 6/8 (75%).In patients affected with digestive system tumors, 68 Ga-FAPI-04 PET/CT resulted in staging changes in more than 46% and therapeutic modifications in 25% of the cases, in particular in patients with HCC and PDAC. In clinical routine, such findings may favor a more widespread adoption of FAP-directed imaging in those tumor types.We aimed to determine the impact of fibroblast activation protein inhibitor (FAPI)–directed molecular imaging on staging and therapeutic management in patients affected with digestive system tumors when compared with guideline-compatible imaging (GCI).Thirty-two patients with tumors of the digestive system were included: colon adenocarcinoma, 2/32 (6.3%); hepatocellular carcinoma (HCC), 6/32 (18.8%); pancreatic duct adenocarcinoma (PDAC), 6/32 (18.8%), and gastroenteropancreatic neuroendocrine neoplasms, 18/32 (56.3%). All patients underwent GCI and 68 Ga-FAPI-04 PET/CT within median 4 days. Staging outcomes and subsequent treatment decisions were compared between GCI and 68 Ga-FAPI-04 PET/CT.Compared with GCI, 68 Ga-FAPI-04 PET/CT led to staging changes in 15/32 patients (46.9%). Among those, downstaging was recorded in 3/15 cases (20.0%) and upstaging in the remaining 12/15 patients (HCC, 4/12 [33.3%]; PDAC, 4/12 [33.3%]; neuroendocrine neoplasms, 3/12 [25%]; colon adenocarcinoma, 1/12 [8.3%]). Therapeutic management was impacted in 8/32 patients (25.0%), including 4 instances of major and 4 instances of minor therapeutic changes. The highest proportion of treatment modifications was observed in patients diagnosed with PDAC and HCC in 6/8 (75%).In patients affected with digestive system tumors, 68 Ga-FAPI-04 PET/CT resulted in staging changes in more than 46% and therapeutic modifications in 25% of the cases, in particular in patients with HCC and PDAC. In clinical routine, such findings may favor a more widespread adoption of FAP-directed imaging in those tumor types.

Background. Cancers of digestive system have high case-fatality rate. It is important to find more appropriate methods in diagnosing and predicting gastrointestinal malignances. And thrombospondin-2 (TSP-2) was reported to have the functions, although results were not identical. So we performed this meta-analysis to clarify the significance of TSP-2 in this area. Methods. PubMed, Embase, Web of Science, Cochrane Library, and Clinicaltrial.gov were searched for relevant studies. Data were extracted from these involved records. For the meta-analysis of diagnostic test, bivariate mixed effect model was used to estimate diagnostic accuracy. For prognosis part, HRs and their 95% CIs were pooled to compare the overall survival (OS) and disease-free survival (DFS) between patients with high TSP-2 and low TSP-2. Results. Nine records were eligible for the analysis of diagnostic test. Pooled results were as follows: sensitivity 0.60 (0.52, 0.68), specificity 0.96 (0.91, 0.98), positive likelihood ratio (PLR) 15.4 (7.3, 32.2), negative likelihood ratio (NLR) 0.42 (0.34, 0.50), and diagnostic odds ratio (DOR) 37 (18, 76). While in prognosis part, 10 articles were included. Patients with increased TSP-2 had shorter OS ( HR = 1.64 , 95% CI = 1.21 -2.22); however, no difference was found in DFS between TSP-2 high and low groups ( HR = 1.44 , 95% CI = 0.28 -7.33). Conclusions. TSP-2, as a diagnostic marker, has a high specificity but a moderate sensitivity. Meanwhile, it plays a role in predicting OS. Therefore, making TSP-2 a routine assay could be beneficial to high-risk individuals and patients with digestive malignances.

This meta-analysis aimed to evaluate the correlation between lncRNA HULC, prognosis and clinicopathological characteristics in patients with digestive system tumors.The relevant literatures were collected through PubMed, Web of Science and Embase up to February 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the prognostic value of HULC in patients with digestive system tumors. The clinicopathological characteristics of HULC in patients were estimated by odds ratios (ORs).A total of 14 studies involving 1312 patients were included. The up-regulated expression level of HULC was associated with poorer overall survival (OS) in patients with digestive system tumors (HR = 1.83, 95% CI: 1.05-3.19,High expression level of HULC is related to OS, TNM stage, differentiation and LNM. Therefore, HULC can be used as a new potential predictor for prognosis and clinicopathological features of patients with digestive system tumors.

Cancer, like other chronic pathologies, is associated with the presence of hypoxic regions due to the uncontrolled cell growth. Under this pathological hypoxic condition, various molecular signaling pathways are activated to ensure cell survival, such as those that govern angiogenesis, erythropoiesis, among others. These molecular processes are very similar to the physiological response caused by exposure to altitude (natural hypobaric systemic hypoxia), the use of artificial hypoxia devices (systemic normobaric simulated hypoxia) or the delivery of vascular occlusion to the extremities (also called local hypoxia by the blood flow restriction technique). "Tumor hypoxia" has gained further clinical importance due to its crucial role in both tumor progression and resistance to treatment. However, the ability to manipulate this pathway through physical exercise and systemic hypoxia-mediated signaling pathways could offer an important range of therapeutic opportunities that should be further investigated.This review is focused on the potential implications of systemic hypoxia combined with exercise in digestive system neoplasms prognosis. Articles included in the review were retrieved by searching among the three main scientific databases: PubMed, Scopus, and Embase.The findings of this review suggest that exercise performed under systemic hypoxic conditions could have a positive impact in prognosis and quality of life of the population with digestive system cancers.Further studies are needed to consider this paradigm as a new potential intervention in digestive oncological population.

International audience; Background: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and treatment. Most patients newly diagnosed with digestive system cancer are aged 65 and over. Methods: We performed a retrospective, observational, multicentre cohort study based on prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer between January 2018 until August 2020 were enroled. Results: Data on 7882 patients were analysed. The first COVID-19 lockdown period led to a 42.4% decrease in newly treated digestive system cancers, and the post-lockdown period was associated with a 17% decrease. The decrease in newly treated digestive system cancer did not differ as a function of age, sex, comorbidities, primary tumour site, and disease stage. The proportion of patients admitted to an emergency department increased during the lockdown period. We do not observe a higher 3-month mortality rate in 2020, relative to the corresponding calendar periods in 2018 and 2019. Conclusion: To avoid a decrease in newly treated cancers during future lockdown periods, access to healthcare will have to be modified. Although 3-month mortality did not increase in any of the patient subgroups, the 2020 cohort must be followed up for long-term mortality.

Background Frailty is common in patients who undergo digestive system tumor surgery. This review aimed to explore the effects of preoperative frailty on multiple outcomes following surgery among patients with digestive system tumors. Methods PubMed (Medline), Embase, Web of Science, and other databases were searched from the inception of each database to April 2021. Meta-analysis or qualitative synthesis was performed to examine the relationship between preoperative frailty and adverse postoperative outcomes. Results A total of 29 studies encompassing 122,548 patients were included. Through meta-analysis, frailty was associated with an increased risk of total complications (risk ratio [RR] 1.44; 95 % confidence interval [CI] 1.39 to 1.50), major complications (RR 1.72; 95 % CI 1.51 to 1.95), 30-d mortality (RR 2.40; 95 % CI 2.14 to 2.70), and 5-year mortality (RR 1.74; 95 % CI 1.35 to 2.24). Through qualitative synthesis, compared with non-frail patients, two studies found that frail patients had a worse quality of life, and three studies reported that frail patients experienced greater rates of non-home discharge. However, two studies demonstrated inconsistent conclusions regarding the relationship between frailty and functional status. Conclusions Preoperative frailty was an important risk factor for multiple adverse postoperative outcomes of patients with digestive system tumors, including objective clinical outcomes and patient-centered outcomes. Future studies focusing on the effects of frailty on patient-centered outcomes such as quality of life and functional status are needed.

The physin family of proteins, synaptophysin (SYP), synaptophysin like 1 (SYPL1), synaptophysin like 2 (SYPL2) and synaptoporin (SYNRP), are tetratransmembrane transport vesicle proteins distributed throughout the digestive system. Of these, SYP is a required marker for histopathologic identification of neuroendocrine neoplasms (NENs), especially in gastroenteropancreatic NENs (GEP-NENs). Recently, bloodstream SYP, i.e., on platelets and circulating tumor cells, has been correlated to clinicopathologic features of GEP-NENs and may have prognostic significance. Serum SYPL1 also represents a promising biomarker for colorectal cancer. This chapter provides an overview of physin structures and potential use as diagnostic, prognostic and therapeutic tools for digestive tract neoplasms.

OBJECTIVE Conversion of normal cells to cancer cells is often accompanied by abnormal synthesis of serum enzymes. Both alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) have been reported to have prognostic value in a variety of malignancies. The aim of this study was to investigate the effect of preoperative serum ALP and LDH levels on the prognosis of patients with periampullary carcinoma who underwent pancreatoduodenectomy (PD). METHODS According to the preoperative ALP or LDH values, 856 cancer patients receiving PD treatment from January 2001 to January 2019 were divided into high-ALP group and low-ALP group or high-LDH group and low-LDH group. Statistical analysis was carried out to study the differences between the high-ALP and low-ALP groups or the high-LDH and low-LDH groups. Furthermore, the possibility of preoperative ALP or LDH as prognostic factor of periampullary carcinoma was investigated. RESULTS In both the high-ALP and the high-LDH groups, the prognosis of patients with periampullary carcinoma who underwent PD was worse than that of the low-ALP and low- LDH group. Even through risk factor analysis, it was found that preoperative ALP and LDH could be independent prognostic factor for patients with periampullary carcinoma who underwent PD. CONCLUSION Preoperative ALP or LDH is an independent risk factor for periampullary carcinoma.

Background For the past two decades, dispute on whether proton pump inhibitor (PPI) leads to digestive tract cancer remains, and emerging studies in recent years still demonstrate inconsistent results, which continues to perpetuate concerns over the safety of PPI use. We performed a systematic review and meta-analysis, with comprehensive evaluation by Bradford Hill criteria of causation, to assess the effect of PPI use on digestive tract cancers. Methods Medline, Embase and Web of Science databases were searched for observational studies published up to 15th January 2021. Pooled relative risks (RRs) were estimated via random effects models. Cumulative defined daily dose- and duration-risk relationships using restricted cubic spline and fractional polynomial models were investigated. Bradford Hill criteria were applied to evaluate causation. PROSPERO Registration: CRD42020211103. Results Thirty-two publications containing 4,355,254 participants were included. PPI use is associated with an increased risk of overall digestive tract cancers (RR = 1.63, 95% confidence interval (CI) 1.33 to 2.00). PPI use is correlated with increased risks of gastric cancer (RR = 1.78, 95% CI 1.38 to 2.31), pancreatic cancer (RR = 1.72, 95% CI 1.05 to 2.82) and liver cancer (RR = 1.62, 95% CI 1.04 to 2.52), but not of esophageal cancer (RR = 2.06, 95% CI 0.65 to 6.57) and colorectal cancer (RR = 1.24, 95% CI 0.93 to 1.66). The association between PPI and digestive tract cancers is stronger in people with minimal exposure. When cumulative defined daily dose or duration increases, the risks decline and become non-significant. Evaluation by Bradford Hill criteria indicates weak evidence of causation. Conclusions A causal relationship between PPI use and digestive tract cancers is not supported by the evidence in the current review. Concerns over carcinogenic side-effects of PPI might be unfounded.

Background Previous research found that the cancer history of an individual’s sibling may be a better indicator than that of the parents. We aim to provide recommendations for opportunistic screening for individuals whose sibling had been diagnosed with cancer. Methods During the physical examination in Cancer Hospital, Chinese Academy of Medical Sciences, 43,300 people were asked if they have at least two siblings who developed cancer. Results A total of 1270 sibling-pairs from 766 families developed cancer, including 367 pairs of brothers (Bro-pairs), 368 pairs of sisters (Sis-pairs), and 535 pairs of brother-and-sister (BroSis-pairs). The mean ages at diagnosis of cancer for the three groups were from 58 to 62 years. More than half of Bro-pairs (55.3%) or Sis-pairs (51.1%) had cancer from the same systemic origin, and more than a quarter of Bro-pairs (28.1%) and Sis-pairs (37.2%) developed the same type of cancer. However, only 36.0% of BroSis-pairs developed cancers from the same systemic origin, and 18.9% developed the same type of cancer. In Bro-pairs and BroSis-pairs, lung cancer and digestive system cancer were the most common cancers, while in Sis-pairs, breast cancer, lung cancer, cervical cancer, liver cancer and thyroid cancer were the most common ones. Conclusions If an individual’s sibling is diagnosed with cancer, the individual should consider participating in opportunistic screening annually, especially for lung cancer and digestive system cancers for both sexes. For sisters, breast cancer, cervical cancer and thyroid cancer should be screened early. Additionally, genetic services are essential for individuals who have siblings with cancer.

Cancers evolve as a result of the accelerated proliferation of cancer cells in a complicated, enriched, and active microenvironment. Tumor microenvironment (TME) components are the master regulators of any step of cancer development. The tumor microenvironment is composed of many cellular and noncellular components that contribute to the evolution of cancer cells. Cancer-associated fibroblasts (CAFs) are activated fibroblasts in the TME that implicate in tumor progression and metastasis dissemination through secretion of oncogenic factors which are carried to the secondary metastatic sites through exosomes. In this review, we aimed to assess the role of CAF-derived exosomes in TME construction and pre-metastatic niche formation in different cancers of the digestive system in order to better understand some important mechanisms of metastasis and provide possible targets for clinical intervention. This review article is divided into two thematic parts explaining the general mechanisms of pre-metastatic niche formation and metastasis and the role of CAF-derived exosomes in different digestive system cancers including colorectal, gastric, esophageal, pancreatic, and liver cancers.

BACKGROUND Tumor of the digestive system is a common malignancy with high morbidity and mortality. Although programmed cell death-1 (PD-1) inhibitors have become an effective treatment strategies for many kinds of tumors, there is still some uncertainty in digestive tumors, including: (I) therapeutic effects of PD-1 inhibitors are relatively limited; (II) responses of digestive system tumors to immunotherapies are highly heterogeneous. In the present study, we investigated the outcomes of PD-1 inhibitors for digestive system tumors in Chinese patients to analyze factors that may affect the effects of immunotherapies in digestive system tumors. METHODS Data were obtained from the Hospital Information System (HIS) of the Department of Digestive Oncology (Henan Cancer Hospital) between January 2019 and December 2019. Inclusion criteria included patients receiving the same PD-1 inhibitor continuously for advanced or recurrent/metastatic digestive system tumors. Indicators including age, sex, clinical diagnosis, height, weight, gene status, PD-1 inhibitors, treatment regimen, medication cycle, efficacy evaluation results, and adverse reactions were analyzed retrospectively. The clinical outcomes were progression-free survival (PFS) and safety. RESULTS A total of 2,767 patients were discharged from HIS, of which 64 (37 male/27 female) were included in this study. Thirty-eight (59.4%) of the patients were aged

Background Mixed adenoneuroendocrine carcinoma is a rare clinical manifestation, especially in the gastric and ampullary. The purpose of this study was to investigate the clinicopathological features and prognosis of mixed adenoneuroendocrine carcinoma in the gastric and ampullary and summarize related treatment suggestions. Methods In all, 32 cases of mixed adenoneuroendocrine carcinoma in the gastric and ampullary that were diagnosed from resected specimens were analyzed from 2009 to 2015. The corresponding demographic, clinicopathological and survival data were retrospectively reviewed. Results The 1-year, 3-year and 5-year survival rates were 78.1%, 28.1 and 9.4%, respectively, and the median overall survival was 28.0 months. In all, 75.0% (24/32) had lymph node metastasis at the time of initial diagnosis. A multivariate analysis revealed that TNM stage (HR 6.444 95%CI 1.477–28.121 P = 0.013), lymph nodes metastasis (HR10.617 95%CI 1.409–79.997 P = 0.022), vascular invasion (HR 5.855 95%CI 1.719–19.940 P = 0.005), grade of the adenocarcinoma component (HR 3.876 95%CI 1.451–10.357 P = 0.007) and CD56 positivity (HR 0.265 95%CI 0.100–0.705 P = 0.008) were independent predictors of overall survival. Conclusions Mixed adenoneuroendocrine carcinoma is an aggressive clinical entity with a poor prognosis. Taking both the neuroendocrine component and the adenocarcinoma component into consideration of optimal treatment is strongly recommended.

In the FIGHTDIGO study, digestive cancer patients with dynapenia experienced more chemotherapy-induced neurotoxicities. FIGHTDIGOTOX aimed to evaluate the relationship between pre-therapeutic handgrip strength (HGS) and chemotherapy-induced dose-limiting toxicity (DLT) or all-grade toxicity in digestive cancer patients. HGS measurement was performed with a Jamar dynamometer. Dynapenia was defined according to EWGSOP2 criteria (

Background & aims: Vitamin C is an antioxidant with a potential role in the prevention of digestive system cancers, but there is yet no consensus whether vitamin C has a causal role in these cancers. The aim of this study was to utilize Mendelian randomization to decipher the potential causal associations of vitamin C with risk of digestive system cancers.Methods: Ten genetic variants previously found to be significantly associated with circulating vitamin C were used as instrumental variables. Effect size estimates for the genetic associations of the vitamin Cassociated genetic variants with six major malignancies of digestive system were obtained from the FinnGen (N = 309 154) and UK Biobank (N = 367 542) studies. Results from the two studies were combined using meta-analysis.Results: Genetically predicted higher circulating vitamin C showed a suggestive association with lower risk of small intestine and colorectal cancer after accounting for multiple testing. The odds ratio per 1 standard deviation increment in circulating vitamin C was 0.55 (95% confidence interval 0.32-0.94; P = 0.029) for small intestine cancer and 0.84 (95% confidence interval 0.73-0.96; P = 0.013) for colorectal cancer. There was a suggestive association between genetically predicted higher circulating vitamin C with lower risk of liver cancer in FinnGen but no association in the meta-analysis (odds ratio 0.69; 95% CI 0.36-1.32; P = 0.265). Genetically predicted circulating vitamin C was not associated with cancers of the esophagus, stomach, or pancreas.Conclusion: This Mendelian randomization study indicates that vitamin C might play a role in the prevention of small intestine and colorectal cancer. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Previous observational case-control studies have shown significant controversy over the impact of dietary intake-related circulating antioxidants on the risk of digestive system tumors. We conducted a two-sample Mendelian randomized (MR) analysis to determine whether there was a significant causal relationship between increased levels of circulating antioxidants and digestive system tumors. Our circulating antioxidants (vitamin C, carotenoids, vitamin A, and vitamin E) were derived from absolute circulating antioxidants and circulating antioxidant metabolites, and their corresponding instrumental variables were screened from published studies. The digestive system tumors we studied included colorectal, gastric, pancreatic, liver, and esophageal cancer, and the corresponding summary GAWS (genome-wide association study) data were obtained from the UK Biobank database. We first evaluated the causal relationship between each tumor and circulating antioxidants and then used meta-analysis to summarize the results of MR analysis of different tumors. No significant associations were noted for genetically predicted circulating antioxidants and higher risk of digestive system tumors in our study. The pooled ORs (odds ratio) are 0.72 (95% CI: 0.46–1.11; β-carotene), 0.93 (95% CI: 0.81–1.08; lycopene), 2.12 (95% CI: 0.31–14.66; retinol), and 0.99 (95% CI: 0.96–1.02; ascorbate) for absolute circulating antioxidants; for circulating antioxidant metabolites, the pooled ORs for digestive system tumors risk per unit increase of antioxidants were 1.29 (95% CI: 0.39–4.28; α-tocopherol), 1.72 (95% CI: 0.85–3.49; γ-tocopherol), 1.05 (95% CI: 0.96–1.14; retinol), and 1.21 (95% CI: 0.97–1.51; ascorbate), respectively. Our study suggested that increased levels of dietary-derived circulating antioxidants did not reduce the risk of digestive system tumors.

Objective Owing to its rarity and heterogeneity, the biological behavior and optimal therapeutic management of mixed neuroendocrine‐non‐neuroendocrine neoplasm (MiNEN) have not been established. Herein, we aimed to evaluate the clinicopathological characteristics and metastatic patterns of MiNEN. Methods Continuous clinicopathological data of MiNEN patients treated at our hospital were retrospectively collected and analyzed. Results This study had enrolled 169 patients since January 2010 to January 2020. Pathological components were assessed in 129 patients with MiNEN (76.3%), and a focal (non‐)neuroendocrine component was observed in 40 patients (23.7%, Regional lymph nodes and distant metastases of MiNEN exhibited distinct metastatic patterns. We recommend that patients with MiNEN undergo aggressive multidisciplinary oncologic management, and an optimal modality should be established based on the NEC component.

Digestive system tumors, which mainly include esophagus, stomach, colorectum, liver, pancreas, bile duct, and some other tumors, often have a poor prognosis. N6-methyladenosine (m6A) has critical functions in development and tumorigenesis and may help improve the molecular mechanisms of digestive system tumors. However, current understanding of the reconstitution of m6A in digestive system tumors is far from comprehensive. Herein, this study systematically analyzed multi-layered genomic characteristics and clinical relevance of m6A regulators in 1906 patients involving seven digestive system tumor types. We discovered that m6A regulators showed extensive genetic changes and highly consistent expression regulation. The m6A expression was closely related to the activity of cancer pathways. At the same time, we also identified m6A regulators significantly related to the common cancer pathways of digestive system tumors and specific cancer pathways of digestive tract and digestive glands. These cancer pathways may explain the prognostic differences of patients with digestive tract tumors. In addition, m6A regulators demonstrated strong potential in prognostic stratification and drug development, especially in multiple research cohorts on pancreatic cancer, pointing to a strong prognostic stratification capability of m6A regulators. Finally, a m6A scoring model significantly related to highly active ubiquitin-mediated proteolysis, mismatch repair, cell cycle, ebasal transcription factors was constructed and had a strong prognostic stratification ability in digestive gland tumors. The score showed a significant negative correlation with the tumor immune microenvironment. This study demonstrated that the similarities and difference of the action mechanism m6A regulators in the digestive tract and digestive gland tumor progression could guide potential drug development.

Objectives This case–control study was aimed to investigate associations between HBV infection and extrahepatic digestive system cancers. Methods The patients of gastric, small intestinal, colonic, rectal, anal, biliary tract, and pancreatic cancers were retrospectively collected between 2016.5 and 2017.12. Simultaneously, the healthy controls were collected from the health check‐up registry, and cancer‐free status was confirmed based on medical records. Propensity score matching was performed to reduce bias. Multinomial logit model and conditional logistic regression model were used to assess the risk of individual cancer according to HBV serological markers and classifications. Results Totally, 4748 patients involving seven cancers, and 57,499 controls were included. After matching, HBsAg was associated with increased risk of gastric cancer (aOR = 1.39, 95% CI: 1.05–1.85), and anti‐HBs served as a protective factor for gastric (aOR = 0.72, 95% CI: 0.61–0.85), colonic (aOR = 0.73, 95% CI: 0.60–0.89), rectal (aOR = 0.73, 95% CI: 0.63–0.85), and pancreatic (aOR = 0.58, 95% CI: 0.42–0.82) cancers. Compared to subgroups with non‐infection and vaccination status, inactive HBsAg carriers and active HBV infection subgroup were correlated with gastric carcinogenesis (aOR = 1.41, 95% CI: 1.03–1.93). However, no clear association was found between HBV infection and other cancers. Conclusions HBV infection was potentially associated with an increased risk of gastric cancer. The development mechanism of HBV‐associated gastric cancer needs to investigate further., This case–control study was aimed to investigate associations between HBV infection and extrahepatic digestive system cancers. Our study revealed that HBV infection was potentially associated with an increased risk of gastric cancer. However, because of the limited ability to establish a causal relationship for case–control study, large‐scale prospective cohort studies are urgencies, and the latent mechanism about HBV extrahepatic carcinogenesis needs to be investigated as well.

Digestive system cancers, including liver, gastric, colon, esophageal and pancreatic cancers, are the leading cause of cancers with high morbidity and mortality, and the question of their clinical treatment is still open. Previous studies have indicated that Ziyuglycoside II (ZYG II), the major bioactive ingredient extract from Sanguisorba officinalis L., significantly inhibits the growth of various cancer cells. However, the selective anti-tumor effects of ZYG II against digestive system cancers are not systemically investigated. In this study, we reported the anti-cancer effect of ZYG II on esophageal cancer cells (OE21), cholangiocarcinoma cells (HuCCT1), gastric cancer cells (BGC-823), liver cancer cells (HepG2), human colonic cancer cells (HCT116), and pancreatic cancer cells (PANC-1). We also found that ZYG II induced cell cycle arrest, oxidative stress and mitochondrial apoptosis. Network pharmacology analysis suggested that UBC, EGFR and IKBKG are predicted targets of ZYG II. EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYG II and both docking simulation and western blot analysis demonstrated that ZYG II was a potential EGFR inhibitor. Furthermore, our results showed synergistic inhibitory effects of ZYG II and chemotherapy 5-FU on the growth of cancer cells. In summary, ZYG II are effective anti-tumor agents against digestive cancers. Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYG II for the treatment of digestive system cancers.

MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating the expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles in cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as a valuable biomarker for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

Digestive system cancer is the most common cause of cancer death in the world. Although cancer treatment options are increasingly diversified, the mortality rate of malignant cancer of the digestive system remains high. Therefore, it is necessary to explore effective cancer treatment methods. Recently, biomimetic nanoparticle delivery systems based on natural cells that organically integrate the low immunogenicity, high biocompatibility, cancer targeting, and controllable, versatile functionality of smart nanocarrier design with natural cells have been expected to break through the bottleneck of tumor targeted therapy. In this review, we focus on the dynamic changes and complex cellular communications that occur

Circular RNAs (circRNAs) are a new series of noncoding RNAs (ncRNAs) that have been reported to be expressed in eukaryotic cells and have a variety of biological functions in the regulation of cancer pathogenesis and progression. The TME, as a microscopic ecological environment, consists of a variety of cells, including tumor cells, immune cells and other normal cells, ECM and a large number of signaling molecules. The crosstalk between circRNAs and the TME plays a complicated role in affecting the malignant behaviors of digestive system cancers. Herein, we summarize the mechanisms underlying aberrant circRNA expression in the TME of the digestive system cancers, including immune surveillance, angiogenesis, EMT, and ECM remodelling. The regulation of the TME by circRNA is expected to be a new therapeutic method.

Background This study aimed to investigate the clinical features, diagnostic criteria, treatment options, and prognosis of patients with gastric schwannoma (GS). Methods We collected the clinical data of all patients pathologically diagnosed with GS in Zhejiang Provincial People's Hospital from May 2012 to October 2021. Results A total of 26 cases of GS were analyzed clinicopathologically, where the sizes of the tumor were found to be in the range of 1–6 cm (mean: 3.16 cm, median: 3.05 cm). A computed tomography (CT) scan analysis revealed that most masses were either moderately progressive or uniformly enhanced. According to ultrasound gastroscopy results, most of them were hypoechoic masses. There were 23 cases of surgery and three cases of endoscopic submucosal tumor dissection. Immunohistochemistry demonstrated that S100 was positive in 26 patients, immunomarker SOX10 was positive in five, whereas CD34, CD117, and SMA were negative in most patients. CK (Pan), Dog-1, and Desmin were also found negative. All 26 cases were followed up after the conclusion of the study where no evidence of recurrence or metastasis was observed. Conclusions GS is a unique form of peripheral schwannoma. The diagnosis of this type of tumor depends on the pathology and immunohistochemistry of the individual. The key to treating this type of tumor is endoscopy and surgery. Follow up and related literature review showed that GS was a benign tumor with little possibility of malignant transformation.

Background It has been previously reported that CD155 is often over-expressed in a variety of cancer types. In fact, it is known to be involved in cancer development, and its role in cancer has been widely established. However, clinical and mechanistic studies involving CD155 yielded conflicting results. Thus, the present study aimed to evaluate overall prognostic value of CD155 in cancer patients, using a comprehensive analysis. Methods Online databases were searched, data was collected, and clinical value of CD155 was evaluated by combining hazard ratios (HRs) or odds ratios (ORs). Results The present study involved meta-analysis of 26 previous studies that involved 4325 cancer patients. These studies were obtained from 25 research articles. The results of the study revealed that increased CD155 expression was significantly associated with reduced OS in patients with cancer as compared to low CD155 expression (pooled HR = 1.772, 95% CI = 1.441–2.178, P < 0.001). Furthermore, subgroup analysis demonstrated that the level of CD155 expression was significantly associated with OS in patients with digestive system cancer (pooled HR = 1.570, 95% CI = 1.120–2.201, P = 0.009), hepatobiliary pancreatic cancer (pooled HR = 1.677, 95% CI = 1.037–2.712, P = 0.035), digestive tract cancer (pooled HR = 1.512, 95% CI = 1.016–2.250, P = 0.042), breast cancer (pooled HR = 2.137, 95% CI = 1.448–3.154, P < 0.001), lung cancer (pooled HR = 1.706, 95% CI = 1.193–2.440, P = 0.003), head and neck cancer (pooled HR = 1.470, 95% CI = 1.160–1.862, P = 0.001). Additionally, a significant correlation was observed between enhanced CD155 expression and advanced tumor stage (pooled OR = 1.697, 95% CI = 1.217–2.366, P = 0.002), LN metastasis (pooled OR = 1.953, 95% CI = 1.253–3.046, P = 0.003), and distant metastasis (pooled OR = 2.253, 95% CI = 1.235–4.110, P = 0.008). Conclusion Altogether, the results of the present study revealed that CD155 acted as an independent marker of prognosis in cancer patients, and it could provide a new and strong direction for cancer treatment.

Background The impact of the stage of cancer on perioperative mortality remains obscure. The purpose of this study was to investigate whether cancer stage influences 30-d mortality for gastric, pancreatic, and colorectal cancers. Methods Data were collected from the National Cancer Database for patients undergoing resections for cancers of the stomach, pancreas, colon, or rectum between 2004 and 2015. The main analysis was conducted among patients with cancer stages 1-3. A sensitivity analysis also included cancer stage 4. Descriptive statistics were used to compare the patients’ baseline characteristics. Generalized linear mixed models were used to evaluate the relationship between stage and 30-d mortality, controlling for other disease-, patient- and hospital-level factors. Pseudo R2 statistics (%Δ pseudo R2) were used to quantify the relative explanatory capacity of the variables to the model for 30-d mortality. All analyses were performed using SAS 9.4. Results The cohort included 24,468, 28,078, 176,285, and 64,947 patients with stomach, pancreas, colon, and rectal cancers, respectively. After adjusting for other variables, 30-d mortality was different by stage for all cancer types examined. The factor most strongly associated with 30-d mortality was age (%Δ pseudo R2 range 14%-39%). The prognostic impact of cancer stage (Stages 1, 2, or 3) on 30-d mortality was comparable to that of the Charlson comorbidity index. Conclusions Cancer stage contributes to explaining differences observed in short-term mortality for gastrointestinal cancers. Short-term mortality models would benefit by including more granular cancer stage, beyond disseminated status alone.

The SARS-CoV-2 (COVID-19) pandemic requires an analysis in the field of oncological surgery, both on the risk of infection, with very relevant clinical consequences, and on the need to generate plans to minimize the impact on possible restrictions on health resources. The AEC is making a proposal for the management of patients with hepatopancreatobiliary (HPB) malignancies in the different pandemic scenarios in order to offer the maximum benefit to patients, minimising the risks of COVID-19 infection, and optimising the healthcare resources available at any time. This requires the coordination of the different treatment options between the departments involved in the management of these patients: medical oncology, radiotherapy oncology, surgery, anaesthesia, radiology, endoscopy department and intensive care. The goal is offer effective treatments, adapted to the available resources, without compromising patients and healthcare professionals safety. (C) 2020 AEC. Published by Elsevier Espana, S.L.U. All rights reserved.

Background The effects of comorbidities on chronic obstructive pulmonary disease (COPD) have been usually studied individually in the past. In this study, we aimed to investigate the comorbidities associated with mortality, the effect of multimorbidity on mortality and other factors associated with mortality among Korean COPD population. Methods The Korean National Health Insurance Service-National Sample Cohort version 2.0, collected between 2002 and 2015, was used. Among COPD patients [entire cohort (EC), N = 12,779], 44% of the participants underwent additional health examination, and they were analysed separately [health-screening cohort (HSC), N = 5624]. Fifteen comorbidities previously reported as risk factors for mortality were studied using Cox proportional hazards regression models. Results Total mortality rates were 38.6 per 1000 person-years (95% CI 37.32–40.01) and 27.4 per 1000 person-years (95% CI 25.68–29.22) in EC and HSC, respectively. The most common causes of death were disease progression, lung cancer, and pneumonia. Only some of the comorbidities had a direct impact on mortality. Multimorbidity, assessed by the number of comorbid diseases, was an independent risk factor of all-cause mortality in both cohorts and was a risk factor of respiratory mortality only in HSC. The Kaplan–Meier analysis showed significant differences in survival trajectories according to the number of comorbidities in all-cause mortality but not in respiratory mortality. Low BMI, old age and male sex were independent risk factors for both mortalities in both cohorts. Conclusions The number of comorbidities might be an independent risk factor of COPD mortality. Multimorbidity contributes to all-cause mortality in COPD, but the effect of multimorbidity is less evident on respiratory mortality.

Objective: Malignant rhabdoid tumor (MRT) is a rare but aggressive malignancy. It has been a long time since data on this tumor have been updated. Methods: We retrospectively reviewed patients from the SEER database who were pathologically diagnosed with MRT and analyzed incidence rates, clinical features and survival using Stata 12.0. Results: In total, 544 patients were included in the epidemiological analysis. There were two peak periods of MRT incidence: patients younger than 4 years and those older than 70 years. Further survival analysis showed that the survival of children (especially younger than 1 year) was markedly worse than that of adults (P

Summary Hepatoid tumors (HT) are rare neoplasms morphologically resembling hepatocellular carcinoma, which arise in several organs other than the liver. A comprehensive molecular profile of this group of neoplasms is still lacking. Genomic characterization of 19 HTs from different organs (three colon HTs, four esophagogastric HTs, four biliary HTs, six genitourinary HTs, two lung HTs) was performed using a multigene next-generation sequencing panel. NGS unraveled a composite molecular profile of HT. Their genetic alterations were clearly clustered by tumor site: (i) colorectal HT displayed microsatellite instability, high tumor mutational burden, mutations in ARID1A/B genes and NCOA4-RET gene fusion (2/3 cases); (ii) gastric HT had TP53 mutations (2/4); (iii) biliary HT displayed loss of CDKN2A (3/4) and loss of chromosome 18 (2/4); (iv) genital HT showed gain of chromosome 12 (3/6); (v) lung HT had STK11 somatic mutations (2/2). The only commonly mutated gene occurring in HT of different sites was TP53 (8/19 cases: colon 2, esophagogastric 2, biliary 2, genital 1, lungs 1). This study shows that most genetic alterations of HT were clustered by site, indicating that context matters. The novel potential targets for HT precision oncology are also clustered based on the anatomic origin. This study shed light on the biology of these rare cancers and may have important consequences for treatment decisions and clinical trial selection for HT patients.

Background: Peripheral neurotoxicity is common in patients with digestive malignancies receiving chemotherapy containing oxaliplatin, and there is still no effective drug to prevent or treat this complication. Methods: Seventy-nine patients receiving chemotherapy containing oxaliplatin were included, and the relationship between chemotherapy regimens, cycles, and cumulative dose of oxaliplatin and peripheral neurotoxicity was analyzed. Patients were divided into two groups of control or intervention. Twenty-eight patients in the control group received routine chemotherapy care, and 51 patients in the intervention group underwent two-week exercise rehabilitation program. Patients’ Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity (FACT/GOG-Ntx), functional tests, and Brief Pain Inventory(BPI) scores as well as interference life scores were assessed before intervention and two weeks after the intervention. Results: In the intervention group, 52.9% patients previously exercised regularly. The FOLFOX regimen was more common in peripheral neurotoxicity (73.4%), and the median oxaliplatin cycles for neurotoxicity was 9 (ranging from 1 to 16). The mean cumulative dose of oxaliplatin was 1080.02 ± 185.22 mg, both the cycles and cumulative dose were positively correlated with the occurrence of peripheral neurotoxicity. Compared with control, the scores of FACT/GOG-Ntx, functional tests, and BPI were significantly decreased in the intervention group (p < 0.05). Conclusion: Chemotherapy cycles and cumulative doses were in relation with OIN , and exercise rehabilitation program could effectively alleviate OIN.

ObjectiveStenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results.DesignIn a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours.ResultsOverall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, pConclusionsDue to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

Introduction: The majority of cancer patients report malnutrition, with a significant impact on patient's outcome. This study aimed to compare how nutritional assessment is conducted across different surgical oncology sub-specialties.Methods: Survey modules were designed for breast, hepato-pancreato-biliary (HPB), upper-gastrointestinal (UGI), sarcoma, peritoneal and surface malignancies (PSM) and colorectal cancer (CRC) surgeries to describe 4 domains: participants' setting, evaluation of clinical factors, use of screening tools and clinical practice. Results were compared among sub-specialties and according to human development index (HDI) in the largest cohorts.Results: Out of 457 answers from 377 global participants (62% European), 35.0% were from breast and 28.9% were from CRC surgeons. Although MDTs management is consistently reported (64-88%), the presence of a nutritionist/dietician ranges from 14.1% to 44.2%. Breast surgeons seldom evaluate albumin (25.6%) and weight loss (30.6%), opposite to HPB, PSM and UGI groups (>70%, p 0.044). Overall, responders declared that the use of screening tools is largely neglected, that nutritional status is often assessed by the surgeons and that nutrition is not consistently modified according to risk factors (range among groups respectively: 1.9%-25.6%, 33.1%-51.4%, 33.1%-60.5%). Less than 20% of breast surgeons assess patients before/after surgery, comparing to >60% of PSM surgeons. However, no statistical differences were documented comparing groups for the majority of the items of the 4 domains. Nutritional evaluation is more often conducted by breast surgeons in medium/low HDI countries comparing very high/high HDI (p 0.04).Conclusions: Nutritional assessment is largely neglected. These results identify target-issues for the implementation of clinical practice. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

To explore potential synergy in effectiveness between metformin and everolimus, 2 inhibitors of the mTOR pathway, for neuroendocrine tumours (NET).A cohort of patients with advanced gastroenteropancreatic or lung NETs treated by everolimus were stratified in to those without diabetes, those with diabetes and without metformin, and those with diabetes with metformin. The primary endpoint was the median progression-free survival (PFS).A total of 213 patients were included, 165 of which were non-diabetic; among diabetic patients, 19 were treated with metformin and 29 with others anti-diabetic drugs. No significant difference in median PFS [95%CI] was found between the three groups: 10.05 months [8.27;11.83] for non-diabetic patients, 15.24 [19.88;49.43] for diabetic w/metformin, and 9.03 months [4.01;14.06] for diabetic w/o metformin group. In univariate analysis, factors significantly associated with longer PFS was a functioning NET, a number of metastatic sites3, the absence of lung metastasis, and an uptake on Octreoscan®, but not the absence of metformin use; only uptake on Octreoscan® remained significant in multivariate analysis.In contrast with the literature, we did not find a synergy between everolimus and metformin in NET. Prospective studies are underway to improve the comprehension of the potential synergy regarding population and tumour type.

Within tumors, chemokines and their cognate receptors are expressed by infiltrated leukocytes, cancerous cells, and related cells of stroma, like tumor-associated fibroblasts and tumor-associated macrophages. In malignancies, the altered expression of chemokines/chemokine receptors governs leukocyte infiltration and activation, epithelial-mesenchymal transition (EMT), cancer cell proliferation, angiogenesis, and metastasis. Non-coding RNAs (ncRNAs) contribute to multiple physiological and pathophysiological processes. Some miRNAs can exert anti-tumorigenic activity in digestive system malignancies by repressing the expression of tumor-promoting chemokines/chemokine receptors or by upregulating tumor-suppressing chemokines/chemokine receptors. However, many miRNAs exert pro-tumorigenic activity by suppressing the expression of chemokines/chemokine receptors or by upregulating tumor-promoting chemokines/chemokine receptors. LncRNA and circRNAs also exert pro- and anti-tumorigenic effects by targeting downstream miRNAs influencing the expression of tumor-promoting and tumor-suppressor chemokines/chemokine receptors. On the other side, some chemokines influence the expression of ncRNAs affecting tumor formation. The current review explains the communications between ncRNAs and chemokines/chemokine receptors in certain digestive system malignancies, such as gastric, colorectal, and pancreatic cancers and hepatocellular carcinoma to gain better insights into their basic crosstalk as well as possible therapeutic modalities.

Background Cell-free and concentrated ascites reinfusion therapy (CART) is a strategy for improving various intractable symptoms due to refractory ascites, including hypoalbuminemia. CART has recently been applied in the treatment of cancer patients. This study was performed to assess the safety of CART in a single cancer institute. Methods We retrospectively reviewed 233 CART procedures that were performed for 132 cancer patients in our institute. Results The median weight of ascites before and after concentration was 4,720 g and 490 g (median concentration rate, 10.0-fold), The median amounts of total protein and albumin were 64.0 g and 32.6 g (median recovery rates, 44.9% and 49.0%), respectively. Thirty-three adverse events (AEs) were observed in 22 (9.4%) of 233 procedures; 30 of these events occurred after reinfusion. The most common reinfusion-related AEs were fever (13 events) and chills (10 events). Univariate analyses revealed no significant relationships between the frequency of AEs and age, sex, appearance of ascites, weight of harvested and concentrated ascites, the ascites processing rate (filtration and concentration), weight of saline used for membrane cleaning, amount of calculated total protein for infusion, or prophylaxis against AEs; the reinfusion rate of ≥ 125 mL/h or ≥ 10.9 g/h of total protein affected the frequency of AEs, regardless of the prophylactic use of steroids. Conclusions The observed AEs were mainly mild reactions after reinfusion, which were related to a reinfusion rate of volume ≥ 125 mL/h, a simple indicator in practice, or total protein ≥ 10.9 g/h. Although our study was retrospective in nature and undertaken in a single institute, this information may be helpful for the management of cancer patients with refractory malignant ascites using CART.

Background Malignant ascites often causes discomfort in advanced cancer patients. Paracentesis is the most common treatment modality, but it requires frequently repeated treatment. Cell-free and concentrated ascites reinfusion therapy (CART) may prolong the paracentesis interval, but controlled trials are lacking. We assessed the feasibility of a randomized controlled trial of CART vs. paracentesis alone for patients with refractory malignant ascites. Methods This study was an open-label, fast-track, randomized controlled, feasibility trial. Patients admitted to four designated cancer hospitals who received no further anticancer treatments were eligible. Patients were randomly assigned 1:1 to a CART arm or control (simple paracentesis) arm. The feasibility endpoint was the percentage of patients who completed the study intervention. Secondary endpoints included paracentesis-free survival, patient’s request on the questionnaire for paracentesis (PRO-paracentesis)-free survival (the period until the patients first reported that they would want paracentesis if indicated), and adverse events. Results We screened 953 patients for eligibility. Of 61 patients with refractory malignant ascites, 21 patients were determined as eligible. Finally, 20 patients consented and were allocated; 18 patients (90%, 95% CI: 68.3–98.8) completed the study intervention. All patients had an ECOG performance status of 3 or 4. The median drained ascites volume was 3,200 mL in the CART arm and 2,500 mL in the control arm. In the CART arm, the median reinfused albumin volume was 12.6 g. Median paracentesis-free survivals were 5 days (95% CI: 2–6) in the CART arm, and 6 days (3–9) in the control arm. Median PRO-paracentesis-free survivals were 4 days (2–5) and 5 days (1–9), respectively. A total of 73% of patients received paracentesis within 2 days from their first request for the next paracentesis. One patient in the CART arm developed Grade 1 fever. Conclusions A fast-track randomized controlled trial of CART for patients with malignant ascites is feasible. The efficacy and safety of CART should be assessed in future trials. PRO-paracentesis-free survival may be a complementary outcome measure with paracentesis-free survival in future trials. Trial registration Registered at University Hospital Medical Information Network Clinical Trial Registry as UMIN000031029. Registered on 28/01/2018.

Neuroendocrine neoplasms (NENs) are a group of disease entities sharing common morphological, ultrastructural and immunophenotypical features, yet with distinct biological behavior and clinical outcome, ranging from benign to frankly malignant. Accordingly, a spectrum of therapeutic options for each single entity is available, including somatostatin analogues (SSA), mTOR-inhibitors, peptide receptor radionuclide therapy (PRRT), non-platinum and platinum chemotherapy. In the last few decades, several attempts have been made to better stratify these lesions refining the pathological classifications, so as to obtain an optimal correspondence between the scientific terminology and, the predictive and prognostic features of each disease subtype, and achieve a global Classification encompassing NENs arising at different anatomical sites. The aim of this review was to analyze, compare and discuss the main features and issues of the latest WHO Classifications of NENs of the lung and the digestive system, in order to point out the strengths and limitations of our current understanding of these complex diseases.

Multiple endocrine neoplasias are rare hereditary syndromes some of them with malignant potential. Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome due to germline variants in the REarranged during Transfection (RET) proto-oncogene. There are two distinct clinical entities: MEN 2A and MEN 2B. MEN 2A is associated with medullary thyroid carcinoma (MTC), phaeochromocytoma, primary hyperparathyroidism, cutaneous lichen amyloidosis and Hirschprung's disease and MEN 2B with MTC, phaeochromocytoma, ganglioneuromatosis of the aerodigestive tract, musculoskeletal and ophthalmologic abnormalities. Germline RET variants causing MEN 2 result in gain-of-function; since the discovery of the genetic variants a thorough search for genotype-phenotype associations began in order to understand the high variability both between families and within family members. These studies have successfully led to improved risk classification of prognosis in relation to the genotype, thus improving the management of the patients by thorough genetic counseling. The present review summarizes the recent developments in the knowledge of these hereditary syndromes as well as the impact on clinical management, including genetic counseling, of both individual patients and families. It furthermore points to future directions of research for better clarification of timing of treatments of the various manifestations of the syndromes in order to improve survival and morbidity in these patients.

Non-scheduled consultation is very frequent among patients with cancer, creating alterations and delays in programmed visits. We describe the incidence of non-scheduled consultations in patients with digestive cancer in our hospital.Descriptive, prospective, non-interventional study. In a six-month period (May-December 2017), non-scheduled visits were chronologically recorded in the medical oncology consultation of digestive tumours of Hospital Juan Ramón Jiménez de Huelva. We performed a descriptive analysis of the variables collected through the statistical program G-STAT v.2.0.Patients with colon or rectal cancer generated most consultations (68.63%). followed by pancreatic (9.15%) and gastric (5.23%). Most patients had metastatic or advanced stage cancer (59.87%) and were under palliative or symptomatic treatment (58.82%). The most frequent reason for consultation was clinical symptoms (47.05%). followed by information demand (18.30 %).Non-scheduled consultations in cancer patients are frequent; they cause interference in scheduled consultations and not always resolved satisfactorily. We propose several measures to reduce the number of non-scheduled consultation in oncology.La demanda de asistencia no programada por parte de los pacientes oncológicos es muy frecuente (1,2) y conllevan alteraciones y retrasos en la actividad ya programada. Describimos la incidencia de consultas no programadas en pacientes con cáncer digestivo de nuestro centro.Estudio descriptivo, prospectivo y sin intervención. Se recogieron cronológicamente en un periodo de 6 meses (15 de mayo al 14 de diciembre de 2017) y utilizando como fuente la historia clínica de los pacientes, las visitas no programadas atendidas en la consulta de oncología médica de tumores digestivos del Hospital Juan Ramón Jiménez de Huelva. Realizamos un análisis descriptivo de las variables recogidas mediante el programa estadístico G-STAT v.2.0.El mayor número de consultas fue realizado por pacientes con cáncer de colon o recto (68,63%), seguidas por los de páncreas (9,15%) y los gástricos (5,23%). La mayoría de los pacientes tenían un cáncer en situación metastásica o avanzada (59,87%) y estaban recibiendo tratamiento paliativo (58,82%) con quimioterapia o sintomático. El motivo de consulta más frecuente fueron los síntomas clínicos (47,05%), seguido por la demanda de información (18,30 %).Se constata una alta demanda de asistencia no programada por parte de los pacientes con cáncer digestivo, que interfiere con la asistencia programada y no siempre se resuelve satisfactoriamente. Se proponen varias medidas para reducir el número de estas consultas.

Tissue biopsies are the gold-standard for investigating the molecular characterization of tumors. However, a "solid" biopsy is an invasive procedure that cannot capture real-time tumor dynamics and may yield inaccurate information because of intratumoral heterogeneity. In this review, we summarize the current state of knowledge about surgical treatment-associated "liquid" biopsy for patients with digestive organ tumors. A liquid biopsy is a technique involving the sampling and testing of non-solid biological materials, including blood, urine, saliva, and ascites. Previous studies have reported the potential value of blood-based biomarkers, circulating tumor cells, and cell-free nucleic acids as facilitators of cancer treatment. The applications of a liquid biopsy in a cancer treatment setting include screening and early diagnosis, prognostication, and outcome and recurrence monitoring of cancer. This technique has also been suggested as a useful tool in personalized medicine. The transition to precision medicine is still in its early stages. Soon, however, liquid biopsy is likely to form the basis of patient selection for molecular targeted therapies, predictions regarding chemotherapy sensitivity, and real-time evaluations of therapeutic effects.

Highlights • The current systematic review analyzed the data from 161 risk estimates in 47 studies involving 5,797,768 participants and 55,162 cases. • Updated evidence suggests that a moderate to high physical activity level is a common protective factor that can significantly lower the overall risk of digestive-system cancer. • Limited evidence suggests that meeting the international physical activity guidelines might not significantly reduce the risk of digestive-system cancer., Background Physical activity (PA) may have an impact on digestive-system cancer (DSC) by improving insulin sensitivity and anticancer immune function and by reducing the exposure of the digestive tract to carcinogens by stimulating gastrointestinal motility, thus reducing transit time. The current study aimed to determine the effect of PA on different types of DSC via a systematic review and meta-analysis. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched for relevant studies in PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure. Using a random effects model, the relationship between PA and different types of DSC was analyzed. Results The data used for meta-analysis were derived from 161 risk estimates in 47 studies involving 5,797,768 participants and 55,162 cases. We assessed the pooled associations between high vs. low PA levels and the risk of DSC (risk ratio (RR) = 0.82, 95% confidence interval (95%CI): 0.79–0.85), colon cancer (RR = 0.81, 95%CI: 0.76–0.87), rectal cancer (RR = 0.88, 95%CI: 0.80–0.98), colorectal cancer (RR = 0.77, 95%CI: 0.69–0.85), gallbladder cancer (RR = 0.79, 95%CI: 0.64–0.98), gastric cancer (RR = 0.83, 95%CI: 0.76–0.91), liver cancer (RR = 0.73, 0.60–0.89), oropharyngeal cancer (RR = 0.79, 95%CI: 0.72–0.87), and pancreatic cancer (RR = 0.85, 95%CI: 0.78–0.93). The findings were comparable between case-control studies (RR = 0.73, 95%CI: 0.68–0.78) and prospective cohort studies (RR = 0.88, 95%CI: 0.80–0.91). The meta-analysis of 9 studies reporting low, moderate, and high PA levels, with 17 risk estimates, showed that compared to low PA, moderate PA may also reduce the risk of DSC (RR = 0.89, 95%CI: 0.80–1.00), while compared to moderate PA, high PA seemed to slightly increase the risk of DSC, although the results were not statistically significant (RR = 1.11, 95%CI: 0.94–1.32). In addition, limited evidence from 5 studies suggested that meeting the international PA guidelines might not significantly reduce the risk of DSC (RR = 0.96, 95%CI: 0.91–1.02). Conclusion Compared to previous research, this systematic review has provided more comprehensive information about the inverse relationship between PA and DSC risk. The updated evidence from the current meta-analysis indicates that a moderate-to-high PA level is a common protective factor that can significantly lower the overall risk of DSC. However, the reduction rate for specific cancers may vary. In addition, limited evidence suggests that meeting the international PA guidelines might not significantly reduce the risk of DSC. Thus, future studies must be conducted to determine the optimal dosage, frequency, intensity, and duration of PA required to reduce DSC risk effectively., Graphical abstract Image, graphical abstract