Development of a Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration of Imaging Features.

BACKGROUND: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems. METHODS: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created. RESULTS: We identified 383 patients with HCC with imaging and survival outcomes, n = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems. CONCLUSIONS: Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC.

Position statement of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) on APC I1307K and cancer risk.

While constitutional pathogenic variants in the APC gene cause familial adenomatous polyposis, APC c.3920T>A; p.Ile1307Lys (I1307K) has been associated with a moderate increased risk of colorectal cancer (CRC), particularly in individuals of Ashkenazi Jewish descent. However, published data include relatively small sample sizes, generating inconclusive results regarding cancer risk, particularly in non-Ashkenazi populations. This has led to different country/continental-specific guidelines regarding genetic testing, clinical management and surveillance recommendations for I1307K. A multidisciplinary international expert group endorsed by the International Society for Gastrointestinal Hereditary Tumours (InSiGHT), has generated a position statement on the APC I1307K allele and its association with cancer predisposition. Based on a systematic review and meta-analysis of the evidence published, the aim of this document is to summarise the prevalence of the APC I1307K allele and analysed the evidence of the associated cancer risk in different populations. Here we provide recommendations on the laboratory classification of the variant, define the role of predictive testing for I1307K, suggest recommendations for cancer screening in I1307K heterozygous and homozygous individuals and identify knowledge gaps to be addressed in future research studies. Briefly, I1307K, classified as pathogenic, low penetrance, is a risk factor for CRC in individuals of Ashkenazi Jewish origin and should be tested in this population, offering carriers specific clinical surveillance. There is not enough evidence to support an increased risk of cancer in other populations/subpopulations. Therefore, until/unless future evidence indicates otherwise, individuals of non-Ashkenazi Jewish descent harbouring I1307K should be enrolled in national CRC screening programmes for average-risk individuals.

Decision-making and regret in patients with germline CDH1 variants undergoing prophylactic total gastrectomy.

INTRODUCTION: Prophylactic total gastrectomy (PTG) can eliminate gastric cancer risk and is recommended in carriers of a germline CDH1 pathogenic variant. PTG has established risks and potential life-long morbidity. Decision-making regarding PTG is complex and not well-understood. METHODS: Individuals with germline CDH1 pathogenic or likely pathogenic variants who underwent surveillance endoscopy and recommended for PTG were evaluated. Factors associated with decision to pursue PTG (PTGpos) or not (PTGneg) were queried. A decision-regret survey was administered to patients who elected PTG. RESULTS: Decision-making was assessed in 120 patients. PTGpos patients (63%, 76/120) were younger than PTGneg (median 45 vs 58 years) and more often had a strong family history of gastric cancer (80.3% vs 34.1%). PTGpos patients reported decision-making based on family history more often and decided soon after diagnosis (8 vs 27 months) compared with PTGneg. Negative endoscopic surveillance results were more common among PTGneg patients. Age >60 years, male sex and longer time to decision were associated with deferring PTG. Strong family history, a family member who died of gastric cancer and carcinoma on endoscopic biopsies were associated with decision to pursue PTG. In the PTGpos group, 30 patients (43%) reported regret which was associated with occurrence of a postoperative complication and no carcinoma detected on final pathology. CONCLUSION: The decision to undergo PTG is influenced by family cancer history and surveillance endoscopy results. Regret is associated with surgical complications and pathological absence of cancer. Individual cancer-risk assessment is necessary to improve pre-operative counselling and inform the decision-making process. TRIAL REGISTRATION NUMBER: NCT03030404.

Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome.

BACKGROUND: Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS. METHODS: 1465 individuals with LS (557 MLH1, 517 MSH2/EPCAM, 299 MSH6 and 92 PMS2) and 5656 CRC-free population-based controls from two independent cohorts were included. A 91-SNP PRS was applied. A Cox proportional hazard regression model with 'family' as a random effect and a logistic regression analysis, followed by a meta-analysis combining both cohorts were conducted. RESULTS: Overall, we did not observe a statistically significant association between PRS and CRC risk in the entire cohort. Nevertheless, PRS was significantly associated with a slightly increased risk of CRC or advanced adenoma (AA), in those with CRC diagnosed <50 years and in individuals with multiple CRCs or AAs diagnosed <60 years. CONCLUSION: The PRS may slightly influence CRC risk in individuals with LS in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS.

First-in-human CLDN18.2 functional diagnostic pet imaging of digestive system neoplasms enables whole-body target mapping and lesion detection.

PURPOSE: Claudin 18.2 (CLDN18.2) is a reliable target for lesion detection and could have clinical implications for epithelial tumors, especially digestive system neoplasms. However, there is no predictive technology for accurate whole-body mapping of CLDN18.2 expression in patients. This study assessed the safety of the 124I-18B10(10L) tracer and the feasibility of mapping whole-body CLDN18.2 expression using PET functional imaging. METHODS: The 124I-18B10(10L) probe was synthesized manually, and preclinical experiments including binding affinity and specific targeting ability were conducted after testing in vitro model cells. Patients with pathologically confirmed digestive system neoplasms were enrolled in an ongoing, open-label, single-arm, first-in-human (FiH) phase 0 trial (NCT04883970). 124I-18B10(10L) PET/CT or PET/MR and 18F-FDG PET were performed within one week. RESULTS: 124I-18B10(10L) was successfully constructed with an over 95% radiochemical yield. The results of preclinical experiments showed that it had high stability in saline and high affinity in CLDN18.2 overexpressing cells (Kd = 4.11 nM). Seventeen patients, including 12 with gastric cancers, 4 with pancreatic cancers, and 1 with cholangiocarcinoma were enrolled. 124I-18B10(10L) displayed high uptake in the spleen and liver, and slight uptake in the bone marrow, lung, stomach and pancreas. The tracer uptake SUVmax in tumor lesions ranged from 0.4 to 19.5. Compared with that in lesions that had been treated with CLDN18.2-targeted therapy, 124I-18B10(10L) uptake was significantly higher in lesions that had not. Regional 124I-18B10(10L) PET/MR in two patients showed high tracer uptake in metastatic lymph nodes. CONCLUSIONS: 124I-18B10(10L) was successfully prepared and exhibited a high binding affinity and CLDN18.2 specificity in preclinical studies. As an FiH CLDN18.2 PET tracer, 124I-18B10(10L) was shown to be safe with acceptable dosimetry and to clearly reveal most lesions overexpressing CLDN18.2. TRIAL REGISTRATION: NCT04883970; URL: https://register. CLINICALTRIALS: gov/ . Registered 07 May 2021.

Dynapenia in digestive cancer outpatients: association with markers of functional and nutritional status (the FIGHTDIGO study).

BACKGROUND: The FIGHTDIGO study determined the feasibility and acceptability of handgrip strength (HGS) measurement in digestive cancer outpatients. PURPOSE: To assess the relationship between muscle strength and markers of functional and nutritional status in this population. DESIGN: 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) < 18 kg/m2 in patients > 70 years old, and BMI < 16 kg/m2 in those < 70 years old. Dynapenia was defined as HGS < 30 kg (men) and < 20 kg (women). Mixed logistic regressions and mixed linear regressions were performed to study factors associated with dynapenia and HGS value, respectively. RESULTS: A total of 879 HGS measurements were analyzed. Dynapenia occurred in 177 measurements (20.1%). BMI and HGS were significantly associated in univariate analysis (p = 0.001). In multivariate analysis, mGPS score (ß = - 0.54 ± 0.31; p = 0.06) and severe malnutrition (ß = - 2.8 ± 1.4; p = 0.08) tended to be associated with HGS. Dynapenia was only associated with functional status impairment in univariate analysis (n = 140/803, 17.4% in ECOG 0 and 1 versus n = 37/76, 58.7% in ECOG 2 and 3; p = 0.002). CONCLUSIONS: Identification of dynapenia using HGS measurement may be useful to predict nutritional vulnerability in digestive cancer outpatients undergoing chemotherapy. Patients could then benefit from nutritional support, adapted physical activity programs, and early therapeutic adjustments. Trial registration ClinicalTrials.gov, NCT02797197.

[Clinical characteristics of digestive system cancers metastatic to the heart].

Objective: To investigate the clinical features of patients with cardiac metastases from digestive system tumors. Methods: This retrospective study collected and analyzed the medical records of patients with cardiac metastases from digestive system tumors who received treatments in the Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and January 2021. Kaplan-Meier method was used for survival analysis. Results: A total of 19 patients were identified. The primary tumors were esophageal squamous cell carcinoma (n=7), gastric or gastroesophageal junction adenocarcinoma (n=6), hepatobiliary cancers (n=3) and colorectal cancers (n=3). 16 patients had pericardial metastases, 2 patients had right atrium metastases, and 1 patient had left ventricle metastasis. The most common symptom was dyspnea, which was present in 8 cases. 7 patients received locoregional treatment, while 11 patients underwent systemic therapies. The median overall survival from diagnosis of primary cancer was 31.4 months, and the median overall survival time from diagnosis of cardiac metastasis was 4.7 months. Conclusion: Cardiac metastasis from digestive system tumors is associated with low incidence and a poor prognosis. Systemic treatment remains the cornerstone of management, while novel anti-tumor drugs may improve therapeutic efficacy.

The Increasing Proportion of Early-Stage Pancreatic Cancer between 2004-2013: A SEER Analysis.

Pancreatic cancer will become the second leading cause of cancer-related death in the United States by 2030. Survival improves when it is identified at an early-stage and resected. Increasing public attention and cross-section imaging may shift detection to earlier stages. We found a small total increase in the proportion of stage-I cancer relative to all stages and a significant increase compared to distant disease in the Surveillance, Epidemiology, and End Results (SEER) database. Despite this, our ability to screen and identify early-stage disease is still lacking. Additional research and population-based interventions are necessary to improve early detection.

Mixed adenoneuroendocrine carcinomas of stomach and ampulla of vater after curative-intent resection: a single center cases series.

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.

The predicted impact and cost-effectiveness of systematic testing of people with incident colorectal cancer for Lynch syndrome.

OBJECTIVES: To evaluate the health impact and cost-effectiveness of systematic testing for Lynch syndrome (LS) in people with incident colorectal cancer (CRC) in Australia. DESIGN, SETTING, PARTICIPANTS: We investigated the impact of LS testing strategies in a micro-simulation model (Policy1-Lynch), explicitly modelling the cost of testing all patients diagnosed with incident CRC during 2017, with detailed modelling of outcomes for patients identified as LS carriers (probands) and their at-risk relatives throughout their lifetimes. For people with confirmed LS, we modelled ongoing colonoscopic surveillance. MAIN OUTCOME MEASURES: Cost-effectiveness of six universal tumour testing strategies (testing for DNA mismatch repair deficiencies) and of universal germline gene panel testing of patients with incident CRC; impact on cost-effectiveness of restricting testing by age at CRC diagnosis (all ages, under 50/60/70 years) and of colonoscopic surveillance interval (one, two years). RESULTS: The cost-effectiveness ratio of universal tumour testing strategies (annual colonoscopic surveillance, no testing age limit) compared with no testing ranged from $28 915 to $31 904/life-year saved (LYS) (indicative willingness-to-pay threshold: $30 000-$50 000/LYS). These strategies could avert 184-189 CRC deaths with an additional 30 597-31 084 colonoscopies over the lifetimes of 1000 patients with incident CRC with LS and 1420 confirmed LS carrier relatives (164-166 additional colonoscopies/death averted). The most cost-effective strategy was immunohistochemistry and BRAF V600E testing (incremental cost-effectiveness ratio [ICER], $28 915/LYS). Universal germline gene panel testing was not cost-effective compared with universal tumour testing strategies (ICER, $2.4 million/LYS). Immunohistochemistry and BRAF V600E testing was cost-effective at all age limits when paired with 2-yearly colonoscopic surveillance (ICER, $11 525-$32 153/LYS), and required 4778-15 860 additional colonoscopies to avert 46-181 CRC deaths (88-103 additional colonoscopies/death averted). CONCLUSIONS: Universal tumour testing strategies for guiding germline genetic testing of people with incident CRC for LS in Australia are likely to be cost-effective compared with no testing. Universal germline gene panel testing would not currently be cost-effective.

Feasibility of systematic handgrip strength testing in digestive cancer patients treated with chemotherapy: The FIGHTDIGO study.

BACKGROUND: Handgrip strength (HGS) is a widely studied noninvasive test. Weak strength (dynapenia) seems to be associated with high morbidity and mortality in different populations, notably oncology populations. Despite this, HGS testing is not used in daily practice in oncology. The study was aimed at evaluating the feasibility and acceptability of HGS testing in patients with digestive cancer treated with ambulatory chemotherapy. METHODS: In this prospective, single-center study, enrolled patients were followed for 6 months. Two consecutive bilateral measures were performed with a Jamar dynamometer during each patient's appointments in the unit for intravenous treatment. A questionnaire was completed by patients and medical team members. RESULTS: There were 203 consecutive patients, and 201 were recruited. In all, 1704 of 1716 measurements (99.3%) were performed, and 201 patients (99.0%) performed at least 1 measure; 190 (94.5%) performed all expected measures. One hundred sixty-four of 171 participating patients (95.9%) found the test easy to perform, and 167 (97.7%) did not find the test restrictive. All of the 14 medical team members found the test easy to perform, unrestrictive, and undisruptive in their daily practice. CONCLUSIONS: HGS testing is routinely feasible, inexpensive, and well accepted by patients and medical teams in an ambulatory digestive cancer unit. Cancer 2018;124:1501-6. © 2017 American Cancer Society.

Dynapenia could predict chemotherapy-induced dose-limiting neurotoxicity in digestive cancer patients.

BACKGROUND: FIGHTDIGO study showed the feasibility and acceptability of handgrip strength (HGS) measure in routine in 201 consecutive patients with digestive cancer treated with ambulatory chemotherapy. The present study focuses on the second aim of FIGHTDIGO study: the relationships between pre-therapeutic dynapenia and chemotherapy-induced Dose-Limiting Toxicities (DLT). METHODS: In this ancillary prospective study, DLT were analyzed in a sub-group of 45 chemotherapy-naive patients. Two bilateral consecutive measures of HGS were performed with a Jamar dynamometer before the first cycle of chemotherapy. Dynapenia was defined as HGS < 30 kg (men) and < 20 kg (women). DLT and/or Dose-Limiting Neurotoxicity (DLN) were defined as any toxicity leading to dose reduction, treatment delays or permanent treatment discontinuation. RESULTS: Two-thirds of chemotherapies were potentially neurotoxic (n = 31 [68.7%]) and 22 patients (48.9%) received FOLFOX (5FU, leucovorin plus oxaliplatin) regimen chemotherapy. Eleven patients (24.4%) had pre-therapeutic dynapenia. The median number of chemotherapy cycles was 10 with a median follow-up of 167 days. Twenty-two patients experienced DLT (48.9%). There was no significant association between pre-therapeutic dynapenia and DLT (p = 0.62). Nineteen patients (42.2%) experienced DLN. In multivariate analysis, dynapenia and tumoral location (stomach, biliary tract or small intestine) were independent risk factors for DLN (HR = 3.5 [1.3; 9.8]; p = 0.02 and HR = 3.6 [1.3; 10.0]; p = 0.01, respectively). CONCLUSIONS: Digestive cancer patients with pre-therapeutic dynapenia seemed to experience more DLN. HGS routine measurement may be a way to screen patients with frailty marker (dynapenia) who would require chemotherapy dose adjustment and adapted physical activity programs. TRIAL REGISTRATION: NCT02797197 June 13, 2016 retrospectively registered.

A nurse-led model at public academic hospitals maintains high adherence to colorectal cancer surveillance guidelines.

OBJECTIVE: To examine the compliance of colorectal cancer surveillance decisions for individuals at greater risk with current evidence-based guidelines and to determine whether compliance differs between surveillance models. DESIGN: Prospective auditing of compliance of surveillance decisions with evidence-based guidelines (NHMRC) in two decision-making models: nurse coordinator-led decision making in public academic hospitals and physician-led decision making in private non-academic hospitals. SETTING: Selected South Australian hospitals participating in the Southern Co-operative Program for the Prevention of Colorectal Cancer (SCOOP). MAIN OUTCOME MEASURES: Proportions of recall recommendations that matched NHMRC guideline recommendations (March-May 2015); numbers of surveillance colonoscopies undertaken more than 6 months ahead of schedule (January-December 2015); proportions of significant neoplasia findings during the 15 years of SCOOP operation (2000-2015). RESULTS: For the nurse-led/public academic hospital model, the recall interval recommendation following 398 of 410 colonoscopies (97%) with findings covered by NHMRC guidelines corresponded to the guideline recommendations; for the physician-led/private non-academic hospital model, this applied to 257 of 310 colonoscopies (83%) (P < 0.001). During 2015, 27% of colonoscopies in public academic hospitals (mean, 27 months; SD, 13 months) and 20% of those in private non-academic hospitals (mean, 23 months; SD, 12 months) were performed more than 6 months earlier than scheduled, in most cases because of patient-related factors (symptoms, faecal occult blood test results). The ratio of the numbers of high risk adenomas to cancers increased from 6.6:1 during 2001-2005 to 16:1 during 2011-2015. CONCLUSION: The nurse-led/public academic hospital model for decisions about colorectal cancer surveillance intervals achieves a high degree of compliance with guideline recommendations, which should relieve burdening of colonoscopy resources.

[Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P<0.05). Conclusions: The second primary cancers of MPC cases initially diagnosed of digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

[Clinical characteristics and outcomes of patients with lung cancer, gastrointestinal cancer and urologic cancer with venous thromboembolism].

Objective: To compare the clinical characteristics and outcomes of patients with lung cancer, gastrointestinal (GI) cancer and urologic cancer with venous thromboembolism (VTE). Methods: From January 2003 to January 2013, 192 lung cancer, GI cancer and urologic cancer patients with VTE were retrospectively evaluated for the clinical characteristics and outcomes. Results: Among 192 patients, 82 cases of lung cancer, 78 cases of GI cancer, 32 cases of urologic cancer were involved. The Eastern Cooperative oncology Group Performance Status score of GI cancer group was significantly higher than those of the lung cancer and urologic cancer groups[(2.4±1.1) vs (2.0±1.4), (1.8±1.0), both P<0.05]. The proportion of smoking patients in lung cancer group was significantly higher than that in GI cancer and urologic cancer groups (79.3% vs 30.8%, 53.1%, both P<0.05), while the proportion of operation was significantly lower than that in the latter two groups (35.4% vs 53.8%, 68.8%, both P<0.05). Pathological types of cancer were mostly adenocarcinoma, and the proportion of adenocarcinoma in lung cancer and GI cancer groups was significantly higher than that in urologic cancer group (76.9%, 73.8% vs 37.9%, both P<0.001). The proportion of moderately and/or poorly differentiated histodifferentiation in the first two groups was significantly higher than that of urologic cancer group (90.0%, 95.7% vs 40.0%, both P<0.001). The proportion of patients with TNM stage Ⅲ-Ⅳ in lung cancer group was significantly higher than that of the urological cancer group (87.0% vs 64.3%, P<0.05). The incidence of VTE in lung cancer group was significantly higher than those of GI cancer and urologic cancer groups within 6 months after tumor diagnosis, chemotherapy and operation (79.3% vs 60.3%, 46.9%; 76.5% vs 48.6%, 36.4%; 92.3% vs 57.9%, 59.1%; all P<0.05). The case fatality rate within one year in lung cancer and GI cancer groups was significantly higher than that in urologic cancer group (51.2%, 52.6% vs 18.8%, both P<0.01). The median survival time of the lung cancer and GI cancer groups was significantly shorter than that of the urological cancer group (P=0.001, 0.010, respectively). Conclusions: Adenocarcinoma, advanced cancer, and poor histodifferentiation are risk factors of VTE in cancer patients. Most events of VTE occur within 6 months after a diagnosis of cancer. The prognosis of lung cancer and GI cancer complicated with VTE is worse than that of urologic cancer with VTE.

Clinical value of octamer-binding transcription factor 4 as a prognostic marker in patients with digestive system cancers: A systematic review and meta-analysis.

BACKGROUND AND AIM: The role of octamer-binding transcription factor 4 (Oct4) has been implicated in the clinical prognosis of various kinds of digestive system cancers, but the results remain controversial. The purpose of this meta-analysis is to assess the potential role of Oct4 as a prognostic marker in digestive system tumors. METHODS: Relevant articles were retrieved from Pubmed, Web of Science, and Cochrane Library up to July 2016. The software Stata 12.0 was used to analyze the outcomes, including overall survival (OS), disease-free survival, recurrence-free survival, and clinicopathological characteristics. RESULTS: A total of 13 eligible studies with 1538 patients were included. Elevated Oct4 expression was significantly associated with poor OS (pooled hazard ratio [HR] = 2.183, 95% confidence interval [CI]: 1.824-2.612), disease-free survival (pooled HR = 1.973, 95% CI: 1.538-2.532), and recurrence-free survival (pooled HR = 2.209, 95% CI: 1.461-3.338) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection method did not alter the significant prognostic value of Oct4. Additionally, Oct4 expression was found to be an independent predictive factor for OS (HR = 2.068, 95% CI: 1.633-2.619). No significant association was found between Oct4 and clinicopathological features of digestive system malignancies. CONCLUSION: This study provided evidence of Oct4 and/or its closely related homolog protein as a predictive factor for patients with digestive system cancers. More large-scale clinical studies on the prognostic value of Oct4 are warranted.

Patterns of health care utilization preceding a colorectal cancer diagnosis are strong predictors of dying quickly following diagnosis.

BACKGROUND: Understanding the predictors of a quick death following diagnosis may improve timely access to palliative care. The objective of this study was to explore whether factors in the 24 months prior to a colorectal cancer (CRC) diagnosis predict a quick death post-diagnosis. METHODS: Data were from a longitudinal study of all adult persons diagnosed with CRC in Nova Scotia, Canada, from 01Jan2001-31Dec2005. This study included all persons who died of any cause by 31Dec2010, except those who died within 30 days of CRC surgery (n = 1885 decedents). Classification and regression tree models were used to explore predictors of time from diagnosis to death for the following time intervals: 2, 4, 6, 8, 12, and 26 weeks from diagnosis to death. All models were performed with and without stage at diagnosis as a predictor variable. Clinico-demographic and health service utilization data in the 24 months pre-diagnosis were provided via linked administrative databases. RESULTS: The strongest, most consistent predictors of dying within 2, 4, 6, and 8 weeks of CRC diagnosis were related to health services utilization in the 24 months prior to diagnosis: i.e., number of specialist visits, number of days spent in hospital, and number of family physician visits. Stage at diagnosis was the strongest predictor of dying within 12 and 26 weeks of diagnosis. CONCLUSIONS: Identifying potential predictors of a short timeframe between cancer diagnosis and death may aid in the development of strategies to facilitate timely and appropriate referral to palliative care upon a cancer diagnosis.

Autophagy-related ncRNAs: Regulatory Roles and Potential Therapeutic Effects in Digestive System Neoplasms.

Among all cancers in the world, the incidence rate of digestive system neoplasms accounts for about 25%, while the mortality rate accounts for about 35%. Difficulty in detecting early digestive system cancers and its poor prognosis are the two main reasons for the high mortality rate. Understanding of the basic cellular processes is of significance and autophagy is one of these processes. Considering the importance of autophagy in pathological state functions, the mechanism of autophagy was initially carried out. In this paper, we will review the molecular mechanisms and biological functions of autophagy-associated ncRNAs in different types of digestive system cancers. Autophagy is a process that supports nutrient cycling and metabolic adaptation accomplished through multi-step lysosomal degradation. It has been suggested that autophagy has a dual role in cancer, which limits tumorigenesis in some stages but promotes tumor progression in others. NcRNAs are also shown to modulate cellular autophagy and thus affect the development of digestive system neoplasms. More and more evidence suggests that the regulation of autophagy by ncRNAs plays a complex role in cancer initiation, progression, metastasis, recurrence, and treatment resistance, which might make ncRNAs therapeutic targets for digestive system neoplasms. While miRNAs participate mainly in post-transcriptional regulation, lncRNAs, and circRNAs usually serve as molecular sponges that have more diverse regulatory functions.