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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.

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.

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.

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.

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.

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

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.

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.

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

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is an emerging procedure for gastric outlet obstruction (GOO) as an alternative to endoscopic stent placement in the duodenum or surgery; however, it is technically challenging. This study aimed to evaluate the safety, success rate, and adverse events rate associated with retrieval anchor-assisted EUS-GE.Data from patients who underwent retrieval anchor-assisted EUS-GE for malignant and benign GOO were retrospectively analyzed. Patients' clinical and demographic characteristics, procedure time, and success and adverse event rates were recorded.A total of 10 patients (6 females; mean age 63.2 ± 5.8 years) were included in our study. Nine cases were malignant and one case was benign GOO. Nine patients received retrievable anchor-assisted EUS-GE for GOO. One patient received retrievable anchor-assisted EUS-GE and concurrent EUS-guided hepatogastrostomy due to the biliary obstruction. There were no complications during any of the procedures. The rate of technical and clinical success was 100%.EUS-GE is a safe and effective procedure for GOO. The retrieval anchor can make EUS-GE easier to perform successfully.

Background Previous experimental and clinical studies have shown that anesthetic agents have varying effects on cancer prognosis; however, the results were inconsistent among these studies. The authors compared overall and recurrence-free survival in patients given volatile or intravenous anesthesia for digestive tract cancer surgery. Methods The authors selected patients who had elective esophagectomy, gastrectomy, hepatectomy, cholecystectomy, pancreatectomy, colectomy, and rectal cancer surgery from July 2010 to March 2018 using the Japanese Diagnosis Procedure Combination database. Patients were divided into a volatile anesthesia group (desflurane, sevoflurane, or isoflurane with/without nitrous oxide) and a propofol-based total intravenous anesthesia group. The authors hypothesized that total intravenous anesthesia is associated with greater overall and recurrence-free survival than volatile anesthesia. Subgroup analyses were performed for each type of surgery. Results The authors identified 196,303 eligible patients (166,966 patients in the volatile anesthesia group and 29,337 patients in the propofol-based total intravenous anesthesia group). The numbers (proportions) of death in the volatile anesthesia and total intravenous anesthesia groups were 17,319 (10.4%) and 3,339 (11.4%), respectively. There were no significant differences between the two groups in overall survival (hazard ratio, 1.02; 95% CI, 0.98 to 1.07; P = 0.28) or recurrence-free survival (hazard ratio, 0.99; 95% CI, 0.96 to 1.03; P = 0.59), whereas instrumental variable analyses showed a slight difference in recurrence-free survival (hazard ratio, 0.92; 95% CI, 0.87 to 0.98; P = 0.01). Subgroup analyses showed no significant difference in overall or recurrence-free survival between the groups in any type of surgery. Conclusions Overall and recurrence-free survival were similar between volatile and intravenous anesthesia in patients having digestive tract surgery. Selection of the anesthetic approach for these patients should be based on other factors. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

OBJECTIVE. The N category has been significantly updated in the 8th edition of the American Joint Committee on Cancer's TNM classification. To ensure correct tumor staging, prognosis, and management, it is critical to be aware of these changes. This article reviews the updated N category, organ-specific regional lymph nodes, and lymphatic drainage pathways for cancers of the digestive system from the esophagus to the anal canal. CONCLUSION. Detection of lymph node involvement may be challenging, and knowledge of nodal characteristics, lymphatic drainage pathways, and imaging modalities is essential to optimize detection rate to ensure accurate staging, prognosis estimation, and streamlined management.

Dose escalation via stereotactic radiation therapy techniques has been necessary for hepatobiliary malignancies in the primary and oligometastatic setting, but such dose escalation is challenging for spine metastases due to spinal cord proximity. Here, we investigate the role of spine stereotactic radiosurgery (SSRS) in the management of such metastases. We retrospectively reviewed patients treated with SSRS to spinal metastases from hepatobiliary malignancies between 2004 and 2017 at our Institution. We used the Kaplan–Meier method to calculate overall survival (OS) and local control (LC) and Cox regression analysis to identify factors associated with disease-related outcomes. We identified 28 patients treated to 43 spinal metastases with SSRS for either HCC or cholangiocarcinoma. The 1-year LC and OS were 85% and 23%, respectively. The median time to death was 6.2 months, while median time to local failure was not reached. Tumor volume > 60 cc (SHR 6.65, p = 0.03) and Bilsky ≥ 1c (SHR 4.73, p = 0.05) predicted for poorer LC, while BED10 > 81 Gy trended towards better local control (SHR 4.35, p = 0.08). Child–Pugh Class (HR 3.02, p = 0.003), higher PRISM Group (HR 3.49, p = 0.001), and systemic disease progression (HR 3.65, p = 0.001) were associated with worse mortality based on univariate modeling in patients treated with SSRS; on multivariate analysis, PRISM Group (HR 2.28, p = 0.03) and systemic disease progression (HR 2.67, p = 0.03) remained significant. Four patients (10%) developed compression deformity and one patient (2%) developed radiation neuritis. SSRS provides durable local control in patients with metastatic hepatobiliary malignancies, with higher BED necessary to ensure excellent LC. PRISM scoring is a promising prognostic tool to aid SSRS patient selection.

Purpose To quantify the occurrence of tumor seeding in computed tomography (CT)-guided high-dose-rate brachytherapy (HDRBT) and to identify potential risk factors. Materials and Methods CT-HDRBT is a minimally invasive therapeutic option for local ablation of unresectable tumors. The procedure involves CT-guided placement of an enclosed catheter and high-dose-rate brachytherapy using iridium-192. Transcutaneous puncture of a tumor with subsequent retraction of the applicator has the potential risk of tumor seeding along the puncture tract. A total of 1,765 consecutive CT-HDRBT procedures were performed at this center between 2006 and 2017 and were retrospectively analyzed. In addition, a distinction was made between whether the puncture tract was irradiated or not. Follow-up imaging datasets were evaluated for tumor seeding along the former puncture tracts. Descriptive and exploratory statistical analyses of the data were performed. Results Tumor seeding was observed in 25 cases (25 of 1,765 cases [1.5%]). A total of 0.008 cases occurred per person-age. Patient age was identified as a potential risk factor with an odds ratio of 1.046 (95% confidence interval, 1.003–1.091; P = .04). There were no differences between whether the puncture tract was irradiated or not (P = .552). Conclusions Tumor seeding along the puncture tract can occur in CT-HDRBT but is rare.

Background The objective of the current study was to define and compare rates of textbook outcomes (TO) among patients undergoing colorectal, lung, esophagus, liver, and pancreatic surgery for cancer at U.S. News & World Report (USNWR) ranked hospitals. Methods Medicare Inpatient Standard Analytic Files 2013-2015 were utilized to examine the relationship of TO and USNWR hospital ratings following surgery for colorectal, lung, esophageal, pancreatic, and liver cancer. TO was defined as no postoperative surgical complications, no prolonged length of hospital stay, no readmission within 90 days after discharge, and no postoperative mortality within 90 days after surgery. Results Among the 35,352 Medicare patients included in the cohort, 16,820 (47.6%) underwent surgery at honor roll hospitals, whereas 18 532 (52.4%) underwent surgery at non-honor roll hospitals. The overall proportion of patients who achieved TO was 50.1%. In examining the clinical outcomes of patients who underwent surgery, there was no difference in the odds of achieving TO at honor roll vs non-honor roll hospitals (colorectal: odds ratio [OR], 0.87; 95% confidence interval [CI], 0.69-1.10; lung: OR, 1.07; 95% CI, 0.87-1.32; esophagus: OR, 1.44; 95% CI, 0.72-2.89; liver: OR, 1.27; 95% CI, 0.87-1.84; pancreas: OR, 1.04; 95% CI, 0.67-1.62). Conclusion and relevance Patients undergoing surgery for lung, esophageal, liver, pancreatic, and colorectal cancer had comparable rates of TO at honor roll vs non-honor roll hospitals. No linear association was observed between hospital position in the rank and postoperative outcomes such as TO indicating that patients should not overly focus on the exact position within USNWR ranked hospitals. These data highlight to patients and physicians that up to one-half of patients undergoing surgery for cancer should anticipate at least one adverse outcome.

Introduction This document is a summary of the French Intergroup guidelines regarding the management of digestive neuroendocrine neoplasms (NEN) published in February 2020 ( www.tncd.org ). Methods All French medical societies involved in the management of NEN took part in this work. Recommendations were graded into four categories (A, B, C or D), according to the level of evidence found in the literature until May 2019. Results The management of NEN is challenging because of their heterogeneity and the increasing complexity of diagnostic and therapeutic procedures. Pathological analysis is required for their diagnostic and prognostic characterization, which mainly relies on differentiation, grade and stage. The two main emergency situations are functioning syndromes and poorly-differentiated carcinoma. Chromogranin A is the main biochemical marker of NET, although of limited clinical interest. Initial characterization relies on morphological and isotopic imaging. The treatment of localized NET relies on watchful follow-up and local or surgical resection depending on its supposed aggressiveness. Treatment options for metastatic disease include surgery, somatostatin analogues, chemotherapy, targeted therapies, organ-driven locoregional therapies and peptide-receptor radionuclide therapy. As specific predictive factors of treatment efficacy are yet to be identified and head-to-head comparisons have not or only rarely been performed, the therapeutic strategy currently depends on prognostic factors. Cumulative toxicity and the impact of treatment on quality of life must be considered since survival is relatively long in most patients with NET. Conclusion These guidelines are proposed to achieve the most beneficial therapeutic strategy in clinical practice as the therapeutic landscape of NEN is becoming ever more complex. These recommendations are permanently being reviewed.

Context.— Epstein-Barr virus is a ubiquitous oncogenic virus. During the past 5 decades, the virus has been linked to several disease entities, both neoplastic and nonneoplastic. Several Epstein-Barr virus–associated conditions affect the digestive organs, ranging from mild transient inflammatory conditions to more debilitating and even fatal diseases. Objective.— To discuss the clinicopathologic aspects of some newly or recently recognized Epstein-Barr virus–related conditions encountered in the digestive system and their therapeutic implications. Data Sources.— Published peer-reviewed literature was reviewed. Conclusions.— This article highlights the importance of recognizing the discussed lesions because they influence the direct clinical management or serve as a potential predictive marker for therapy.

Objectives A platinum/etoposide doublet is standard first-line therapy for poorly differentiated neuroendocrine carcinoma (PD NEC); however, evidence to guide treatment beyond first-line regimens is lacking. This study aimed to evaluate the efficacy of second-line regimens in PD NEC. Methods We performed a retrospective analysis of patients treated with second-line chemotherapy for PD NEC. Inclusion criteria were previous first-line therapy with platinum/etoposide, extrapulmonary PD NEC, and follow-up data. The primary end points were overall survival (OS) and progression-free survival (PFS) after second-line therapy. Secondary end points included OS and PFS from first-line therapy. Results Sixty-four patients were included. The median OS from initiation of second-line therapy was 6.2 months (95% confidence interval [CI], 4.9-8.9). The median PFS was 2.3 months (95% CI, 2.0-3.2). No second-line regimen showed a statistically significant difference in OS or PFS. There was a significant increase in OS for cisplatin first-line regimens compared with carboplatin (17.0 months [95% CI, 12.5-22.6] vs 11.7 months [95% CI, 8.0-14.0]). Conclusions The efficacy of current second-line therapy in PD NEC is poor. No second-line regimen showed statistically significant superiority. Cisplatin was associated with longer OS regardless of second-line regimen or age. However, unmeasured confounders such as performance status or comorbidities may explain this effect.

OBJECTIVE The study objectives were to characterize surgical outcomes for malignant small bowel obstruction (MaSBO) as compared to other small bowel obstructions (SBO) and to develop a prediction model for postoperative mortality for MaSBO. SUMMARY BACKGROUND DATA MaSBO is a morbid complication of advanced cancers for which the optimal management remains undefined. METHODS Patients who underwent surgery for MaSBO or SBO were identified from the National Surgical Quality Improvement Program (2005-2017). Outcomes [30-day morbidity, unplanned readmissions, mortality, postoperative length of stay (LOS)] were compared between propensity score-matched MaSBO and SBO patients. An internally validated prediction model for mortality in MaSBO patients was developed. RESULTS Of 46,706 patients, 1612 (3.5%) had MaSBO. Although MaSBO patients were younger than those with SBO (median 63 vs 65 years, P < 0.001), they were otherwise more clinically complex, including a higher proportion with recent weight loss (22.0% vs 4.0%, P < 0.001), severe hypoalbuminemia (18.6% vs 5.2%, P < 0.001), and cytopenias. After matching (N = 1609/group), MaSBO was associated with increased morbidity [odds ratio (OR) 1.2, P = 0.004], but not readmission (OR 1.1, P = 0.48) or LOS (incidence rate ratio 1.0, P = 0.14). The odds of mortality were significantly higher for MaSBO than SBO (OR 3.3, P < 0.001). A risk-score model predicted postoperative mortality for MaSBO with an optimism-adjusted Brier score of 0.114 and area under the curve of 0.735. Patients in the highest-risk category (11.5% of MaSBO population) had a predicted mortality rate of 39.4%. CONCLUSION Surgery for MaSBO is associated with substantial morbidity and mortality, necessitating careful patient evaluation before operative intervention.

The use of 18F-fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) is well established in the evaluation of alimentary tract malignancies. This review of the literature and demonstration of correlative images focuses on the current role of PET/CT in the diagnosis (including pathologic/clinical staging) and post-therapy follow-up of esophageal, gastric, and colorectal cancers. PET/CT provides utility in the management of esophageal cancer, including detection of distant disease prior to resection. In gastric cancer, PET/CT is useful in detecting solid organ metastases and in characterizing responders vs. non-responders after neoadjuvant chemotherapy, the latter of which have poorer overall survival. In patients with GIST tumors, PET/CT also determines response to imatinib therapy with greater expedience as compared to CECT. For colorectal cancer, PET/CT has proven helpful in detecting hepatic and other distant metastases, treatment response, and differentiating post-radiation changes from tumor recurrence. Our review also highlights several pitfalls in PET/CT interpretation of alimentary tract lesions.

Background The results of genetic association studies regarding cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) polymorphisms and digestive system malignancies were controversial. The authors designed this meta-analysis to more precisely estimate relationships between CTLA-4 polymorphisms and digestive system malignancies by pooling the results of related studies. Methods The authors searched PubMed, Embase, Web of Science, and CNKI for eligible studies. Thirty-one eligible studies were pooled analyzed in this meta-analysis. Results The pooled meta-analysis results showed that genetic distributions of rs231775, rs4553808, and rs733618 polymorphisms among patients with digestive system malignancies and controls differed significantly. Moreover, genotypic distribution differences were also observed for rs231775 polymorphism among patients with colorectal cancer/pancreatic cancer and controls, for rs4553808 and rs5742909 polymorphisms among patients with gastric cancer and controls, for rs3087243 polymorphism among patients with liver cancer and controls, and for rs733618 polymorphism among patients with colorectal cancer and controls in pooled meta-analyses. Conclusions This meta-analysis suggested that rs231775 polymorphism was associated with predisposition to colorectal cancer and pancreatic cancer, rs4553808 and rs5742909 polymorphisms were associated with predisposition to gastric cancer, rs3087243 polymorphism was associated with predisposition to liver cancer, and rs733618 polymorphism was associated with predisposition to colorectal cancer.

International audience; Introduction: Endoscopic stenting for malignant gastroduodenal outlet obstruction (MGOO) is described as ineffective and not long-lasting despite a few favorable studies. This study aimed to evaluate the clinical outcomes of a large series of patients in a tertiary center. Methods: A single-center retrospective study was performed using data collected from all patients who received palliative duodenal self-expandable metal stents between January 2011 and December 2016. The primary endpoints were patient diet after the first duodenal procedure (Gastric Outlet Obstruction Scoring System, GOOSS) and clinical success. The secondary endpoints were the median patency duration (calculated according to the Kaplan-Meier method) and the cumulative incidence of reintervention. Results: Two-hundred twenty patients were included. The increase in the GOOSS score was significant (p < 0.001), and the clinical success rate was 86.3%. The median estimated patency duration was 9.0 months [6.5-29.1]. Patients with pancreatic adenocarcinoma had significantly longer patency durations (p = 0.02). The estimated cumulative probability of a second duodenal procedure after 4 months was 13%. Conclusions: In this large series of patients who underwent duodenal stenting for MGOO, we observed significant changes in GOOSS scores, a relatively long patency duration compared to findings in previous series, and a low probability of subsequent duodenal procedures, primarily due to a low median overall survival time (4 months).

To prove that covered stents are more efficacious than uncovered stents regarding patency, safety, enabling of chemotherapy, and survival in percutaneous palliation of malignant infrahilar biliary obstruction.After failed endoscopic treatment, 154 patients with obstructive jaundice caused by unresectable infrahilar malignancy were randomly allocated to receive an expanded polytetrafluoroethylene and fluorinated ethylene propylene-covered or an uncovered nitinol stent. Occlusion rate, patency, and survival were assessed. Safety and clinical success in terms of chemotherapy were compared.Three patients were excluded post hoc. Fifteen patients died within 7 d and were excluded from patency analysis. Occlusion rates were 32% (21 of 66) for covered and 29% (20 of 70) for uncovered stents (P = .7). Estimated median patency durations were 308 d (95% confidence interval [CI], 178-438 d) for covered and 442 d (95% CI, 172-712 d) for uncovered stents (P = .1). Serious adverse events (P = 1.0) and 30-day mortality (P = .5) were equivalent between groups. At hospital discharge, median bilirubin reduction of 8 mg/dL was found in both groups (P.001). In the covered stent group, 35 patients (48%) received palliative chemotherapy, vs 29 (37%) in the uncovered stent group (P = .2). Estimated median survival times were 96 days (95% CI, 68-124 d) with covered stents and 75 days (95% CI, 42-108 d) with uncovered stents (P = .6).In malignant infrahilar biliary obstruction not amenable to endoscopy, no improvement in patency or survival with percutaneously placed covered stents could be confirmed. Covered and uncovered stent types exhibit similar safety profiles and clinical success rates.

The FIGHTDIGO study determined the feasibility and acceptability of handgrip strength (HGS) measurement in digestive cancer outpatients. To assess the relationship between muscle strength and markers of functional and nutritional status in this population. In this prospective study, a total of 201 patients were followed during 6 months and were asked to perform HGS measurement at each hospitalization. Anthropometric measurements, laboratory tests, and performance status (PS) evaluation were collected. The modified Glasgow Prognostic Score (mGPS) was calculated using CRP and albumin levels. Severe malnutrition was defined as body mass index (BMI) 70 years old, and BMI

Background Patients with inflammatory bowel disease are at increased risk of extracolonic cancers. Little is known regarding this risk following total colectomy [TC]. Methods Patients who underwent TC for inflammatory bowel disease in Denmark during 1977–2013 were identified from the Danish National Patient Registry. Incidence rates of extracolonic cancers were determined through record linkage to the Danish Cancer Registry and compared with expected incidence rates in the general population. Standardized incidence ratios [SIRs] were calculated as the observed vs expected cancer incidence. Results In total, 4430 patients (3441 with ulcerative colitis [UC]; 989 with Crohn’s disease [CD]) were followed for 54,183 person-years after TC. Following their surgery, 372 patients were diagnosed with extracolonic cancer compared to 331 expected [SIR = 1.1 (95% confidence interval {CI}: 1.0–1.2)]. The risk of extracolonic cancer overall was increased among patients with CD and TC (SIR = 1.5 [95% CI: 1.2–1.8]), but not among patients with UC and TC (SIR = 1.0 [95% CI: 0.9–1.2]). Patients with UC and TC had a higher risk of intestinal extracolonic cancer (SIR = 2.0 [95% CI: 1.4–2.7]). Patients with CD and TC had a higher risk of smoking-related cancers (SIR = 1.9 [95% CI: 1.2–2.9]), intestinal extracolonic cancer (SIR = 3.1 [95% CI: 1.6–5.5]) and immune-mediated cancers (SIR = 1.5 [95% CI: 1.0–2.1]). Conclusion Patients with CD and TC had a higher risk of extracolonic cancer overall compared to the general population, while patients with UC and TC did not. Site-specific cancer risk varied according to inflammatory bowel disease type.

Background/aim Additional primary malignancy (APM) risk is increasing with improved prognosis of cancer survivors. In order to clarify risk factors and patients susceptible to develop APMs, we investigated the clinical features, prognosis, and approaches for diagnosis and treatment in these patients. Patients and methods Among 874 patients newly diagnosed with gastrointestinal tract (GIT) or hepato-biliary-pancreatic (HBP) cancers between 2011 and 2014, 124 with a synchronous and/or metachronous APM were identified. Patient characteristics, time interval between the malignancies, clue to detect APMs, treatment approaches, and prognosis were investigated. Results Patients with APMs were older and predominantly male. Half of the metachronous APMs were detected within 3 years after the first primary malignancy (PM). The main clue to detect synchronous and metachronous APMs was preoperative screening for current PM, and follow-up of prior PM, respectively. There was no significant difference in the overall survival between colon cancer patients with or without APMs. Conclusion Multiple PMs were present in 14.2% of patients. Male and old age were identified to be risk factors for APM. Pre-operative screening and post-operative regular follow-ups are important for detecting synchronous or metachronous APMs.

To examine the changes in exenterative surgery over three decades analysing oncological outcomes and whether changes in surgical approach have led to improved patient outcomes.Advances in surgical technology, perioperative care and pattern of disease recurrence have coincided with an evolutionary change in exenterative surgery.A review of a prospectively maintained databases of pelvic exenteration surgery from 1988 to 2018 at two high volume specialised institutions. The total cohort was divided into three major time points (1988-2004, 2005-2010 and 2011 to 2018) to allow comparative analysis. Primary endpoints were overall survival in primary and recurrent disease at each time point. Secondary endpoints included anastomotic leak, blood transfusion, ileus, wound infection rates and evolution of case complexity. Data were analysed using R with a p 0.05 considered significant.Six hundred and seventy patients underwent exenterative surgery. In 2011-2018 there was an increase in resection of recurrent malignancy with a continuous increase in GI malignancies resected over each time period(p 0.001,0.01) and a reduction in gynaecological malignancy(p 0.001). A significant increase in sacrectomy, pelvic sidewall resection and ileal conduit reconstruction was observed (p 0.01,0.001).In 2005-2010 patients had increased rates of ileus and anastomotic leak(p 0.05). Patients undergoing resection for primary disease had improved overall survival at time points 1988-2004 and 2011-2018 compared to those with recurrent disease(p = 0.007,0.001). Overall survival was significantly improved in patients with primary versus recurrent disease(p = 0.022).There has been a significant improvement in survival in patients undergoing pelvic exenteration surgery from primary disease. Case complexity has increased without significant morbidity.

The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated using CIBERSORT. The least absolute shrinkage and selection operator (LASSO) analysis was carried out to identify important immune predictors. By comparing immune cell compositions in 801 tumor samples and 46 normal samples, we constructed the diagnostic immune score (DIS), showing high specificity and sensitivity in the training (area under the receiver operating characteristic curve [AUC] = 0.929), validation (AUC = 0.935), and different cancer type cohorts (AUC > 0.70 for all). We also established the prognostic immune score (PIS), which was an effective prognostic factor for relapse‐free survival in training, validation, and entire cohorts (P, Our study comprehensively analyzed the utility of consideration of immune cells in the diagnosis and prognosis of digestive system cancers. The diagnostic immune score and prognostic immune score signature might serve as biomarkers for early diagnosis and predicting survival.

The WHO classification of digestive system tumours presented in the first volume of the WHO classification of tumours series, 5th edition, reflects important advancements in our understanding of tumours of the digestive system (Table ​(Table1).1). For the first time, certain tumour types are defined as much by their molecular phenotype as their histological characteristics; however, in most instances histopathological classification remains the gold standard for diagnosis. The WHO classification of tumours series is designed to be used worldwide, including those settings where a lack of tissue samples or of specific technical facilities limits the pathologist's ability to rely on molecular testing. Table 1 Selected changes within the new classification of tumours of the digestive system

Background and objectives Despite quality evidence supporting postoperative extended venous thromboembolism prophylaxis (eVTEp) following abdominopelvic cancer surgery, baseline use of eVTEp at our institution was 3%. Our project aim was to improve the proportion of patients prescribed eVTEp following surgery for gynecologic, hepatobiliary, and colorectal cancers by a 30% absolute increase. Methods We performed an interrupted time series study using quality improvement methodology. Postoperative order sets, pre-printed prescriptions, process checklists, and multimodal education were introduced. Process and outcome data were collected and analyzed on statistical process control charts. Results We included 324 patients with gynecologic and hepatobiliary cancers. Despite efforts to include them, the colorectal team did not participate. The monthly mean order set-use was 58% (SD = 14%), by specialty: gynecology 79%, hepatobiliary 47%. The proportion of patients prescribed eVTEp increased from 3% to 70% (SD = 14%). The target goal was surpassed and sustained by both cohorts. Patient compliance was 73% (n = 117/160, SD = 16%). Of those who stopped eVTEp early, 45% (n = 14/31) objected because of the injectable nature. Bleeding events were infrequent (0.6%, n = 2/324). Conclusions Three process changes and multimodal education resulted in a significant increase in eVTEp use. Failure to identify improvement champions limited project expansion to colorectal patients. Patient compliance was largely limited by the injectable nature of the medication.

Introduction Streptozocin can impair renal function. The purpose of this study was to evaluate the evolution of renal function in patients receiving this anti-mitotic for the treatment of locally advanced/metastatic digestive well differentiated neuroendocrine tumours. Methods A prospective and a retrospective cohort of patients with normal baseline renal function were analysed. The primary endpoint was the incidence of a decrease in the estimated glomerular filtration rate ≥ 25% during treatment. Secondary endpoints were the evaluation of glomerular filtration rate changes, the impact of combined nephrotoxic treatments, other toxicities, compliance, and the objective response rate. Results After screening 142 patients, 27 were included in the prospective and 84 in the retrospective cohort. A decrease in estimated glomerular filtration rate ≥ 25% was observed in 32 patients (30%): respectively four (15.4%) and 28 patients (34.1%) among respectively 26 and 82 patients with numerous measures (P = 0.0097). Altogether, 39 patients (35%) experienced grade 1–2 renal toxicity, while no grade 3−4 occurred in the prospective and 1 occurred in the retrospective cohort. Renal toxicity was more frequent in the retrospective cohort with a less careful follow up. As best responses, objective response was achieved in 27% of patients with pancreatic primary tumours, disease control in 78.9% of patients with pancreatic primary tumours, in 87% of those with small bowel tumours and in 72.7% of patients with other primary locations. Conclusions Strongly recommended for pancreatic NET, streptozocin is associated with frequent mild renal toxicity but low occurrence of renal impairment in patients with baseline normal renal function and under adequate hydration.

Human leukocyte antigen-G (HLA-G) conveys immunological tolerance at the maternal-foetal interface. HLA-G expression by tumour cells may also play such a role, resulting in tumour immune evasion, making HLA-G a potential target for immunotherapies. The aim of this review was to determine to what extent it is justified that HLA-G expression is considered as a target for immune checkpoint inhibiting therapy by critically assessing the association between HLA-G expression by carcinomas and clinical outcome of patients. The used HLA-G-detecting mAb, HLA-G quantification methods and statistically significant HLA-G-associated clinicopathological parameters are discussed. Tumour HLA-G expression correlated with poor clinical outcome in breast, esophageal, gastric and hepatocellular carcinoma patients. Tumour HLA-G expression was not associated with clinical outcome in ovarian and oral carcinoma patients. Cervical, colorectal, lung, and pancreatic carcinoma patients presented discrepant and therefore inconclusive results regarding the association between tumour HLA-G expression and clinical outcome. These disparities might partly be the result of differences in the methodological approach to quantify HLA-G expression between studies. Therefore, implementation of universal methodological procedures is strongly advised. Overall, HLA-G expression did not univocally result in poor clinical outcome of carcinoma patients. This implies that tumour HLA-G expression is not necessarily part of an inhibited tumour-immune response and tumour progression. Consequently, it remains elusive whether HLA-G expression by carcinomas functions as an immune checkpoint molecule affecting a tumour-immune response. It may also reflect derailed control of gene expression in tumours, with no real functional consequences.

Background & Aims In patients with celiac disease, gluten triggers an immune reaction that damages small intestinal villi and may increase long-term risk of gastrointestinal cancer. However, the health impacts of gluten in the general population are understudied. We aimed to examine the association between gluten intake and risk of digestive system cancers among individuals without celiac disease. Methods We leveraged longitudinal data from three prospective cohorts, Nurses’ Health Study (1984-2018, 73,166 women aged 65.1±10.8 years), Nurses’ Health Study II (1991-2017, 90,423 women aged 49.1±8.2 years), and Health Professionals Follow-Up Study (1986-2016, 42,617 men aged 64.8±10.8 years). Using Cox proportional hazards regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of digestive system cancers according to quintiles of gluten intake assessed from food frequency questionnaires. Results During 4,801,513 person-years of follow-up, we documented 6,231 incident digestive system cancer cases among three cohorts. After adjusting for a wide-range of risk factors, including body mass index, physical activity, diet quality, gluten intake was not associated with an increased risk of digestive system cancer, with a HR (95% CI) of 0.94 (0.87, 1.02) comparing the highest to the lowest quintile of gluten intake (p-trend=0.05). Similar null associations were found for individual digestive system cancers: oral cavity and oropharyngeal cancer, esophageal cancer, stomach cancer, small intestine cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, and liver cancer. Conclusions Gluten intake was not associated with risk of digestive system cancers in adults without celiac disease. Restricting dietary gluten is unlikely to be beneficial to the prevention of digestive system cancers in the general population.

Background Gastrointestinal diseases account for considerable health care use and expenditures. We estimated the annual burden, costs, and research funding associated with gastrointestinal, liver, and pancreatic diseases in the United States. Methods We generated estimates using data from National Ambulatory Medical Care Survey, National Hospital Ambulatory Medical Care Survey, Nationwide Emergency Department Sample, National Inpatient Sample, Kids’ Inpatient Database, Nationwide Readmissions Database, Surveillance, Epidemiology, and End Results program, National Vital Statistics System, Centers for Disease Control Wide-ranging Online Data for Epidemiologic Research, MarketScan Commercial Claims and Encounters data, MarketScan Medicare Supplemental data, United Network for Organ Sharing registry, Medical Expenditure Panel Survey, and National Institutes of Health. Results Gastrointestinal health care expenditures totaled $119.6 billion dollars in 2018. Annually, there were more than 36.8 million ambulatory visits for gastrointestinal symptoms and 43.4 million ambulatory visits with a primary gastrointestinal diagnosis. Hospitalizations for a principal gastrointestinal diagnosis accounted for more than 3.8 million admissions with 403,699 readmissions. A total of 22.2 million gastrointestinal endoscopies were performed and 284,844 new gastrointestinal cancers diagnosed. Gastrointestinal diseases and cancers caused 255,407 deaths. The National Institutes of Health supported $3.1 billion dollars (7.5% of the NIH budget) for gastrointestinal research in 2020. Conclusion Gastrointestinal diseases are responsible for millions of health care encounters and hundreds of thousands of deaths which annually costs billions of dollars in the US. To reduce the high burden of gastrointestinal diseases, focused clinical and public health efforts, supported by additional research funding, are warranted.

Hypoxia is prominent in solid tumors and a recognized driver of malignancy. Thus far, targeting tumor hypoxia has remained unsuccessful. Myo-inositol trispyrophosphate (ITPP) is a re-oxygenating compound without apparent toxicity. In preclinical models, ITPP potentiates the efficacy of subsequent chemotherapy through vascular normalization. Here, we report the results of an unrandomized, open-labeled, 3 + 3 dose-escalation phase Ib study (NCT02528526) including 28 patients with advanced primary hepatopancreatobiliary malignancies and liver metastases of colorectal cancer receiving nine 8h-infusions of ITPP over three weeks across eight dose levels (1'866-14'500 mg/m2/dose), followed by standard chemotherapy. Primary objectives are assessment of the safety and tolerability and establishment of the maximum tolerated dose, while secondary objectives include assessment of pharmacokinetics, antitumor activity via radiological evaluation and assessment of circulatory tumor-specific and angiogenic markers. The maximum tolerated dose is 12,390 mg/m2, and ITPP treatment results in 32 treatment-related toxicities (mostly hypercalcemia) that require little or no intervention. 52% of patients have morphological disease stabilization under ITPP monotherapy. Following subsequent chemotherapy, 10% show partial responses while 60% have stable disease. Decreases in angiogenic markers are noted in ∼60% of patients after ITPP and tend to correlate with responses and survival after chemotherapy., Restoring oxygenation in hypoxic tumors might lead to favorable oncological outcome of patients if combined with standard multimodal therapy regimens. Here the authors report a phase Ib clinical trial of anti-hypoxic myo-inositol trispyrophosphate (ITPP) in hepato-pancreato-biliary neoplasms.

The impact of myosteatosis on the outcomes of digestive malignancies has gained great attention recently. However, studies on the impact of myosteatosis show inconsistent results. We conducted a meta-analysis to clarify the relationship between myosteatosis and the overall survival of digestive cancer patients. The systematic literature search was conducted on PubMed/MEDLINE, Web of Science, and Embase from inception through March 27, 2021. Meta-analysis was performed using the random-effects model. Out of 3451 studies screened, 47 studies including 21,194 patients passed the screening criteria. The average prevalence of myosteatosis was 46.4%. Patients with myosteatosis had 44% increased mortality risk compared with non-myosteatosis patients (HR: 1.44, 95% CI: 1.33-1.55, P.05). The predictive value of myosteatosis held regardless of country zone, study design, statistical model, Newcastle-Ottawa Scale (NOS) scores, treatment, sample size, and tumor stage. Nevertheless, the predictive value of myosteatosis was only evident for patients with esophagogastric cancers, cholangiocarcinoma/pancreatic cancers, or colorectal cancers. Overall, the results of this meta-analysis were robust based on sensitivity, subgroup, meta-regression, and trial sequential analyses and suggested that myosteatosis predicted worse overall survival (OS) in digestive malignancies patients.