Risk of colorectal neoplasia after removal of conventional adenomas and serrated polyps: a comprehensive evaluation of risk factors and surveillance use.

BACKGROUND: Surveillance colonoscopy after polyp removal is recommended to prevent subsequent colorectal cancer (CRC). It is known that advanced adenomas have a substantially higher risk than non-advanced ones, but optimal intervals for surveillance remain unclear. DESIGN: We prospectively followed 156 699 participants who had undergone a colonoscopy from 2007 to 2017 in a large integrated healthcare system. Using multivariable Cox proportional hazards regression we estimated the subsequent risk of CRC and high-risk polyps, respectively, according to index colonoscopy polyps, colonoscopy quality measures, patient characteristics and the use of surveillance colonoscopy. RESULTS: After a median follow-up of 5.3 years, we documented 309 CRC and 3053 high-risk polyp cases. Compared with participants with no polyps at index colonoscopy, those with high-risk adenomas and high-risk serrated polyps had a consistently higher risk of CRC during follow-up, with the highest risk observed at 3 years after polypectomy (multivariable HR 5.44 (95% CI 3.56 to 8.29) and 8.35 (95% CI 4.20 to 16.59), respectively). Recurrence of high-risk polyps showed a similar risk distribution. The use of surveillance colonoscopy was associated with lower risk of CRC, with an HR of 0.61 (95% CI 0.39 to 0.98) among patients with high-risk polyps and 0.57 (95% CI 0.35 to 0.92) among low-risk polyps. Among 1548 patients who had high-risk polyps at both index and surveillance colonoscopies, 65% had their index polyps in the proximal colon and 30% had index and interval polyps in the same segments. CONCLUSION: Patients with high-risk polyp findings were at higher risk of subsequent CRC and high-risk polyps and may benefit from early surveillance within 3 years. The subsite distribution of the index and recurrent high-risk polyps suggests the contribution of incomplete resection and missed lesions to the development of interval neoplasia.

Post-diagnostic multivitamin supplement use and colorectal cancer survival: A prospective cohort study.

BACKGROUND: Use of multivitamin supplements has been associated with lower incidence of colorectal cancer (CRC). However, its influence on CRC survival remains unknown. METHODS: Among 2424 patients with stage I-III CRC who provided detailed information about multivitamin supplements in the Nurses' Health Study and Health Professionals Follow-up Study, the authors calculated multivariable hazard ratios (HRs) of multivitamin supplements for all-cause and CRC-specific mortality according to post-diagnostic use and dose of multivitamin supplements. RESULTS: During a median follow-up of 11 years, the authors documented 1512 deaths, among which 343 were of CRC. Compared to non-users, post-diagnostic users of multivitamin supplements at a dose of 3-5 tablets/week had lower CRC-specific mortality (HR, 0.55; 95% confidence interval [CI], 0.36-0.83, p = .005), and post-diagnostic users at doses of 3-5 and 6-9 tablets/week had lower all-cause mortality (HR, 0.81; 95% CI, 0.67-0.99, p = .04; HR, 0.79; 95% CI, 0.70-0.88), p < .001). The dose-response analysis showed a curvilinear relationship for both CRC-specific (pnonlinearity < .001) and all-cause mortality (pnonlinearity = .004), with the maximum risk reduction observed at 3-5 tablets/week and no further reduction at higher doses. Compared to non-users in both pre- and post-diagnosis periods, new post-diagnostic users at dose of <10 tablets/week had a lower all-cause mortality (HR, 0.81; 95% CI, 0.71-0.94, p = .005), whereas new users at a dose of ≥10 tablets/week (HR, 1.58; 95% CI, 1.07-2.33) and discontinued users (HR, 1.35; 95% CI, 1.14-1.59) had a higher risk of mortality. CONCLUSIONS: Use of multivitamin supplements at a moderate dose after a diagnosis of nonmetastatic CRC is associated with lower CRC-specific and overall mortality, whereas a high dose (≥10 tablets/week) use is associated with higher CRC-specific mortality.

Use of surveillance colonoscopy among individuals with removal of high-risk polyps according to the US Multi-Society Task Force recommendations.

BACKGROUND: Individuals with colorectal polypectomy are recommended to undergo surveillance colonoscopies at certain intervals to prevent subsequent colorectal cancer. Use of postpolypectomy surveillance according to the 2006 US Multi-Society Task Force (USMSTF) recommendations in an integrated health care system was investigated. METHODS: Use of surveillance colonoscopies was prospectively assessed among 3691 patients with removal of high-risk polyps at a screening colonoscopy during 2007-2012 in the Mass General Brigham Colonoscopy Cohort. With the follow-up up to 2017, the compliance with, overuse, and underuse of postpolypectomy surveillance according to the 2006 USMSTF recommendations was assessed. Surveillance use according to demographic factors was also investigated. RESULTS: During a median follow-up of 4.4 years (5th percentile, 95th percentile, 1.0, 9.9) 2360 (64%) patients had undergone a surveillance colonoscopy, among whom 758 (21%) were considered compliant with the USMSTF recommendations. A substantial underuse of surveillance colonoscopies of 62% was observed. Older age and lower income were associated with a higher incidence of underuse, whereas having a family history of colorectal cancer were associated with lower incidence of underuse. Overuse of surveillance colonoscopies was present in 17% of patients but showed no significant associations with demographic factors. CONCLUSION: Substantial underuse of surveillance in patients with high-risk polyps was observed, particularly those with low income and older age. Efforts are needed to improve delivery and use of surveillance colonoscopy. PLAIN LANGUAGE SUMMARY: The US Multi-Society Task Force recommends follow-up surveillance colonoscopy after polyp removal in the bowel, with intervals depending on the most severe findings. Adherence to surveillance recommendations in a large study with up to 10 years of follow-up among patients with high-risk polyps was investigated. Only 21% of patients adhered to the surveillance recommendations, whereas 62% showed delayed or no use of surveillance. Findings highlight the need for improved use of surveillance colonoscopy among patients at high risk of colorectal cancer.

Adherence to a healthy lifestyle in relation to colorectal cancer incidence and all-cause mortality after endoscopic polypectomy: A prospective study in three U.S. cohorts.

It remains unknown whether maintenance of a healthy lifestyle after endoscopic polypectomy could still confer benefit for colorectal cancer (CRC) incidence and mortality. In this study, we defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption and diet (range, 0-5). We used Cox proportional hazards regression to estimate the hazard ratios (HRs) for the associations of healthy lifestyle score and individual lifestyle factors with CRC incidence and all-cause mortality. During a median of 10 years of follow-up of 24 668 participants who underwent endoscopic polypectomy, we documented 161 CRC cases and 4857 all-cause deaths. A higher healthy lifestyle score after endoscopic polypectomy was associated with lower risk of CRC and all-cause mortality. Compared with individuals with 0 to 1 healthy lifestyle factors, those with 2, 3 and 4 to 5 healthy lifestyle factors had a HR for CRC risk of 0.86 (95% confidence interval [CI], 0.60-1.24), 0.73 (95% CI, 0.47-1.14) and 0.52 (95% CI, 0.27-1.01), respectively (Ptrend  = .03). The corresponding HR (95% CI) for all-cause mortality was 0.83 (95% CI, 0.76-0.90), 0.63 (95% CI, 0.56-0.70) and 0.56 (95% CI, 0.48-0.65), respectively (Ptrend < .0001). In the joint analysis of pre- and postpolypectomy periods, patients with a healthy postpolypectomy lifestyle had a lower incidence of CRC regardless of their prepolypectomy exposure, whereas those with a healthy lifestyle in both periods had a lower mortality than those with an unhealthy lifestyle in either period. In conclusion, adherence to a healthy lifestyle after polypectomy may confer significant benefit for CRC prevention and reduction in all-cause mortality.

Circulating liver function markers and colorectal cancer risk: A prospective cohort study in the UK Biobank.

Evidence links the liver to development of colorectal cancer (CRC). However, it remains unknown how liver function may influence CRC risk in the general population. We conducted a prospective cohort study in the UK Biobank of 375 693 participants who provided blood samples in 2006 to 2010. Circulating levels of liver function markers (alanine transaminase [ALT], aspartate transaminase [AST], total bilirubin [TBIL], gamma glutamyltransferase [GGT], alkaline phosphatase [ALP], total protein [TP] and albumin [ALB]) were measured. Incident cancer cases were identified through linkage to the national cancer registry up to 2019. Repeated biomarker measurements were available from a subset of 11 320 participants who were re-assessed in 2012 to 2013. After a median follow-up of 10.0 years, we documented 2662 cases of CRC. Circulating levels of ALT, AST, TBIL, GGT, TP and ALB at baseline were inversely associated with CRC risk (P < .01), with multivariable hazard ratio (95% confidence interval) comparing decile 10 vs 1 of 0.62 (0.51-0.75), 0.63 (0.53-0.75), 0.85 (0.72-1.02), 0.74 (0.61-0.89), 0.70 (0.59-0.84) and 0.66 (0.55-0.79), respectively. Strengthened associations were found after recalibration for repeated measurements. The associations appeared stronger for proximal colon cancer than distal colon cancer and rectal cancer, but consistent for early-, mid- and late-onset CRC. In a large cohort of general population, the UK Biobank, higher circulating levels of ALT, AST, TBIL, GGT, TP and ALB, largely within the normal range, were associated with a lower risk of CRC. The findings support a link between liver function and CRC, and may spur future research on the gut-microbiota-liver axis.

Broccoli sprout supplementation in patients with advanced pancreatic cancer is difficult despite positive effects-results from the POUDER pilot study.

Pancreatic ductal adenocarcinoma is a highly aggressive malignancy with short survival and limited therapeutic options. Broccoli sulforaphane is a promising new treatment due to the results of recent epidemiological, experimental and patient studies. Upon approval from the ethics committee and registration at ClinicalTrials.gov, 40 patients with palliative chemotherapy were placed into a placebo and treatment group in an unblinded fashion. Fifteen capsules with pulverized broccoli sprouts containing 90 mg/508 µmol sulforaphane and 180 mg/411 µmol glucoraphanin or methylcellulose were administered daily for up to 1 year. Twenty-nine patients were included in the treatment group and 11 patients were in the placebo group; these patients were followed for up to 1 year. The patient characteristics, overall survival and feasibility were assessed. Compared to those of the placebo group, the mean death rate was lower in the treatment group during the first 6 months after intake (day 30: 0%/18%, day 90: 0%/25%, and day 180: 25%/43%), and Kaplan-Meier analysis revealed a higher survival rate. There was a high drop-out rate (72% in the treatment group and 55% in the placebo group) after 1 year. We concluded from the Karnofsky index that the broccoli sprouts did not impact patient's self-care and overall abilities severely. The intake of 15 capsules daily was difficult for some patients, and the broccoli sprouts sometimes increased digestive problems, nausea and emesis. We did not obtain statistically significant results (p = 0.291 for the endpoint at day 180), but the knowledge about the feasibility is the basis for the development of new sulforaphane drugs.

Clinical features and surgical outcomes of fibrolamellar hepatocellular carcinoma: retrospective analysis of a single-center experience.

BACKGROUND: Clinicopathological features and surgical outcomes of patients with fibrolamellar hepatocellular carcinoma (FL-HCC) are underreported. The aim of this study is to describe clinical characteristics and surgical outcomes for patients with this rare tumor to raise awareness among clinicians and surgeons. METHODS: Retrospective review of records of a tertiary referral center and specialized liver unit was performed. Out of 3623 patients who underwent liver resection, 366 patients received surgical treatment for HCC; of them, eight (2.2%) had FL-HCC and were resected between October 2001 and December 2018. RESULTS: Eight patients (3 males and 5 females) with FL-HCC (median age 26 years) underwent primary surgical treatment. All patients presented with unspecific symptoms or were diagnosed as incidental finding. No patient had cirrhosis or other underlying liver diseases. Coincidentally, three patients (37.5%) had a thromboembolic event prior to admission. The majority of patients had BCLC stage C and UICC stage IIIB/IVA; four patients (50%) presented with lymph node metastases. The median follow-up period was 33.5 months. The 1-year survival was 71.4%, and 3-year survival was 57.1%. Median survival was at 36.4 months. Five patients (62.5%) developed recurrent disease after a median disease-free survival of 9 months. Two patients (25.0%) received re-resection. CONCLUSION: FL-HCC is a rare differential diagnosis of liver masses in young patients. Since the prognosis is limited, patients with incidental liver tumors or lesions with suspicious features in an otherwise healthy liver should be presented at a specialized hepatobiliary unit. Thromboembolism might be an early paraneoplastic symptom and needs to be elucidated further in the context of FL-HCC.

HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is sensitive to interferon (IFN)-based therapy, whereas hepatitis B virus (HBV) infection is not. It is unclear whether HBV escapes detection by the IFN-mediated immune response or actively suppresses it. Moreover, little is known on how HBV and HCV influence each other in coinfected cells. We investigated interactions between HBV and the IFN-mediated immune response using HepaRG cells and primary human hepatocytes (PHHs). We analyzed the effects of HBV on HCV replication, and vice versa, at the single-cell level. METHODS: PHHs were isolated from liver resection tissues from HBV-, HCV-, and human immunodeficiency virus-negative patients. Differentiated HepaRG cells overexpressing the HBV receptor sodium taurocholate cotransporting polypeptide (dHepaRGNTCP) and PHHs were infected with HBV. Huh7.5 cells were transfected with circular HBV DNA genomes resembling viral covalently closed circular DNA (cccDNA), and subsequently infected with HCV; this served as a model of HBV and HCV coinfection. Cells were incubated with IFN inducers, or IFNs, and antiviral response and viral replication were analyzed by immune fluorescence, reverse-transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assays, and flow cytometry. RESULTS: HBV infection of dHepaRGNTCP cells and PHHs neither activated nor inhibited signaling via pattern recognition receptors. Incubation of dHepaRGNTCP cells and PHHs with IFN had little effect on HBV replication or levels of cccDNA. HBV infection of these cells did not inhibit JAK-STAT signaling or up-regulation of IFN-stimulated genes. In coinfected cells, HBV did not prevent IFN-induced suppression of HCV replication. CONCLUSIONS: In dHepaRGNTCP cells and PHHs, HBV evades the induction of IFN and IFN-induced antiviral effects. HBV infection does not rescue HCV from the IFN-mediated response.

Use of a hydrophilic coating wire reduces significantly the rate of central vein punctures and the incidence of pneumothorax in totally implantable access port (TIAP) surgery.

BACKGROUND: Insertion of a Totally Implantable Access Port (TIAP) can be performed either via Central Vein Puncture (CVP) or Brachiocephalic Vein Cut-down (venous section-VS). The primary success rate of TIAP implantation using VS rarely ever achieves 100%. The objective of this study was to describe a modified VS approach using a hydrophilic coated wire (TVS). METHODS: From 01.01.2015 to 31.12.2015, all patients receiving TIAP implantations were screened. During this time, all patients in whom the primary VS procedure was found to be unsuccessful were analysed. RESULTS: In 2015, 1152 patients had TIAP implantations performed by 24 different surgeons. Of these, 277 patients needed a second line rescue strategy either by CVP (n = 69) or TVS (n = 208). There were no statistically significant differences regarding demographics or indication for TIAP implantation between CVP and TVS. The operation time and the qualification of the operating surgeon between CVP and TVS did not differ significantly. After the introduction of the guidewire with a hydrophilic coated wire, the need for CVP decreased significantly from 12.7% to 8.8% (p < 0.0001). In patients receiving CVP as a second line rescue strategy, the incidence of pneumothorax (n = 3 patients (4.3%)) was significantly higher compared to patients with TVS as a second line rescue strategy (n = 1 patient (0.48%), p = 0.02). CONCLUSION: The use of a hydrophilic coated wire significantly decreased the number of CVP and the incidence of pneumothorax. TVS is a safe and successful second-line rescue strategy.

Incidence, Risk Factors, and Prognosis of Patients with Hepatocellular Carcinoma and Brain Metastases.

OBJECTIVE: Brain metastases significantly impact the clinical course of patients with hepatocellular carcinoma (HCC). This study aimed to examine the age-related incidence, demographics, and survival of patients with HCC and brain metastases. METHODS: Data of HCC patients from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) Registry were screened for the presence of brain metastases. They were stratified by age and ethnicity. Multivariable logistic and Cox regression analyses were used to identify factors associated with brain metastases and those with overall survival (OS) and liver cancer-specific survival (CSS), respectively. RESULTS: A total of 141 HCC patients presenting with brain metastases were identified, accounting for 0.35% of all HCC patients and 2.37% of patients with metastatic disease. Among all HCC patients, the incidence rate was the highest among patients aged 30-49 years old (0.47%). Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African-American patients presented with a significantly lower disease-specific survival [median time: 1 month; interquartile range (IQR): 0-3.0 months)]. Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases [odds ratio (OR): 12.62, 95% confidence interval (CI): 8.40-18.97] but was not associated with a worse OS or CSS among those with brain metastases. CONCLUSION: This study identified the age-related incidence and risk factors of brain metastases in HCC patients. These results may contribute to the consideration of brain screening among patients with initial metastatic HCC with lung or bone metastases, and influence the counseling of this patient population regarding their prognosis.

Association of gallstone disease with risk of colorectal cancer: a systematic review and meta-analysis of observational studies.

BACKGROUND: Numerous studies have assessed the association of gallstones or cholecystectomy (CE) with risk of colorectal cancer (CRC). However, the findings are mixed. OBJECTIVE: To systematically review and meta-analyse the association between the presence of gallstone disease (GD), or CE and the incidence of CRC. Secondary endpoints were the risk based on type of exposure, study design, tumour subsites and sex. METHODS: PubMed and EMBASE were searched from September 2020 to May 2021. The protocol was registered on the Open Science Foundation Platform. We identified and classified studies according to their design into prospective cohort, population-based case-control, hospital-based case-control and necropsy studies reporting CRC incidence among individuals with diagnosed GD or after CE (or both). Among 2157 retrieved studies, 65 (3%) met the inclusion criteria. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Data were extracted by two independent reviewers. We evaluated the quality of the study according to the Newcastle-Ottawa Scale and only studies with a score of 6 and above were included in the final analyses. We pooled log-transformed odds ratios/risk ratios from the available adjusted models to estimate a summary relative risk (RR) and 95% confidence interval (CI) in a random-effects model. The primary outcome was overall CRC incidence. We also conducted secondary analyses according to sex and CRC subsites (proximal colon, distal colon and rectum). The outcome was measured by RRs with 95% CIs. RESULTS: The overall association of GD and/or CE with CRC was RR = 1.15 (1.08; 1.24), primarily driven by hospital-based case-control studies [RR = 1.61 (1.29; 2.01)], whereas a more modest association was found in population-based case-control and cohort studies [RR = 1.10 (1.02; 1.19)]. Most hospital-based case-control and necropsy studies reported estimates that were adjusted for age and sex only, leaving room for residual confounding; therefore we restricted to population-based case-control and cohort studies for our subsequent analyses. Similar associations were found for women [RR = 1.21 (1.05; 1.4) and men (RR = 1.24 (1.06; 1.44)]. When assessed by CRC subsites, GD and CE were primarily associated with higher risk of proximal colon cancer [RR = 1.16 (1.07; 1.26)] but not distal colon cancer [RR = 0.99 (0.96; 1.03)] or rectal cancer [RR = 0.94 (0.89; 1.00)]. CONCLUSIONS: Gallstones are associated with a modestly increased risk of colon cancer, primarily in the proximal colon.

Continuous versus interrupted abdominal wall closure after emergency midline laparotomy: CONTINT: a randomized controlled trial [NCT00544583].

BACKGROUND: High-level evidence regarding the technique of abdominal wall closure for patients undergoing emergency midline laparotomy is sparse. Therefore, we conducted a randomized controlled trial (RCT) to evaluate the efficacy and safety of two commonly applied abdominal wall closure strategies after primary emergency midline laparotomy. METHODS/DESIGN: CONTINT was a multi-center pragmatic open-label exploratory randomized controlled parallel trial. Two different abdominal wall closure strategies in patients undergoing primary midline laparotomy for an emergency surgical intervention with a suspected septic focus in the abdominal cavity were compared: the continuous, all-layer suture and the interrupted suture technique. The primary composite endpoint was burst abdomen within 30 days after surgery or incisional hernia within 12 months. As reliable data on this composite primary endpoint were not available for patients undergoing emergency surgery, it was planned to initially recruit 80 patients and conduct an interim analysis after these had completed the 12 months follow-up. RESULTS: From August 31, 2009, to June 28, 2012, 124 patients were randomized of whom 119 underwent surgery and were analyzed according to the intention-to-treat (ITT) principal. The primary composite endpoint did not differ between the continuous suture (C: 27.1%) and the interrupted suture group (I: 30.0%). None of the individual components of the primary endpoint (reoperation due to burst abdomen after 30 days (C: 13.5%, I: 15.1%) and reoperation due to incisional hernia (C: 3.0%, I:11.1%)) differed between groups. Time needed for fascial closure was longer in the interrupted suture group (C: 12.8 ± 4.5 min, I: 17.4 ± 6.1 min). BMI was associated with burst abdomen during the first 30 days with an OR of 1.17 (95% CI 1.04-1.32). CONCLUSION: This RCT showed no difference between continuous suture with slowly absorbable suture versus interrupted rapidly absorbable sutures after primary emergency midline laparotomy in rates of postoperative burst abdomen and incisional hernia after one year. However, the trial was stopped after the interim analysis due to futility as there was no chance to show superiority of one suture technique.

Development and validation of a risk prediction model for post-polypectomy colorectal cancer in the USA: a prospective cohort study.

Background: Effective risk stratification tools for post-polypectomy colorectal cancer (PPCRC) are lacking. We aimed to develop an effective risk stratification tool for the prediction of PPCRC in three large population-based cohorts and to validate the tool in a clinical cohort. Methods: Leveraging the integrated endoscopic, histopathologic and epidemiologic data in three U.S population-based cohorts of health professional (the Nurses' Health Study (NHS) I, II and Health Professionals Follow-up Study (HPFS)), we developed a risk score to predict incident PPCRC among 26,741 patients with a polypectomy between 1986 and 2017. We validated the PPCRC score in the Mass General Brigham (MGB) Colonoscopy Cohort (Boston, Massachusetts, U.S) of 76,603 patients with a polypectomy between 2007 and 2018. In all four cohorts, we collected detailed data on patients' demographics, endoscopic history, polyp features, and lifestyle factors at polypectomy. The outcome, incidence of PPCRC, was assessed by biennial follow-up questionnaires in the NHS/HPFS cohorts, and through linkage to the Massachusetts Cancer Registry in the MGB cohort. In all four cohorts, individuals who were diagnosed with CRC or died before baseline or within six months after baseline were excluded. We used Cox regression to calculate the hazard ratio (HR), 95% confidence interval (CI) and assessed the discrimination using C-statistics and reclassification using the Net Reclassification Improvement (NRI). Findings: During a median follow-up of 12.8 years (interquartile range (IQR): 9.3, 16.7) and 5.1 years (IQR: 2.7, 7.8) in the NHS/HPFS and MGB cohorts, we documented 220 and 241 PPCRC cases, respectively. We identified a PPCRC risk score based on 11 predictors. In the validation cohort, the PPCRC risk score showed a strong association with PPCRC risk (HR for high vs. low, 3.55, 95% CI, 2.59-4.88) and demonstrated a C-statistic (95% CI) of 0.75 (0.70-0.79), and was discriminatory even within the low- and high-risk polyp groups (C-statistic, 0.73 and 0.71, respectively) defined by the current colonoscopy surveillance recommendations, leading to a NRI of 45% (95% CI, 36-54%) for patients with PPCRC. Interpretation: We developed and validated a risk stratification model for PPCRC that may be useful to guide tailored colonoscopy surveillance. Further work is needed to determine the optimal surveillance interval and test the added value of other predictors of PPCRC beyond those included in the current study, along with implementation studies. Funding: US National Institutes of Health, the American Cancer Society, the South-Eastern Norway Regional Health Authority, the Deutsche Forschungsgemeinschaft.

Mediterranean diet related metabolite profiles and cognitive performance.

BACKGROUND & AIMS: Evidence suggests that adherence to the Mediterranean diet (MedDiet) affects human metabolism and may contribute to better cognitive performance. However, the underlying mechanisms are not clear. OBJECTIVE: We generated a metabolite profile for adherence to MedDiet and evaluated its cross-sectional association with aspects of cognitive performance. METHODS: A total of 1250 healthy Greek middle-aged adults from the Epirus Health Study cohort were included in the analysis. Adherence to the MedDiet was assessed using the 14-point Mediterranean Diet Adherence Screener (MEDAS); cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. A targeted metabolite profiling (n = 250 metabolites) approach was applied, using a high-throughput nuclear magnetic resonance platform. We used elastic net regularized regressions, with a 10-fold cross-validation procedure, to identify a metabolite profile for MEDAS. We evaluated the associations of the identified metabolite profile and MEDAS with cognitive tests, using multivariable linear regression models. RESULTS: We identified a metabolite profile composed of 42 metabolites, mainly lipoprotein subclasses and fatty acids, significantly correlated with MedDiet adherence (Pearson r = 0.35, P-value = 5.5 × 10-37). After adjusting for known risk factors and accounting for multiple testing, the metabolite profile and MEDAS were not associated with the cognitive tests. CONCLUSIONS: A plasma metabolite profile related to better adherence to the MedDiet was not associated with the tested aspects of cognitive performance, in a middle-aged Mediterranean population.

A Multidisciplinary Approach to the Management of Fibrolamellar Carcinoma: Current Perspectives and Future Prospects.

Fibrolamellar carcinoma (FLC) is a rare primary liver tumor affecting predominantly younger and otherwise healthy patients. Typically, FLC presents with advanced disease due to the paucity of typical symptoms and no history of underlying liver disease. Depending on tumor characteristics and the patient's general condition, surgical treatment is the most promising treatment modality. Aggressive resection and liver transplantation have been utilized and are presently indispensable curative treatment options. Under certain circumstances surgical resection is also possible for metachronous metastases or local recurrence. Recent tumor biology discoveries have contributed to improved diagnostic specificity and systemic treatment options.

Factors Influencing Overall Survival for Patients with Fibrolamellar Hepatocellular Carcinoma: Analysis of the Surveillance, Epidemiology, and End Results Database.

BACKGROUND: The study aimed to develop a nomogram to predict overall survival (OS) for patients with FLC using a national database. METHODS: The Surveillance, Epidemiology, and End Results database of the National Cancer Institute was reviewed to identify FLC cases with histological confirmation between 2004 and 2014. Cox proportional hazards models were used to identify factors associated with OS. The validation of the nomogram was performed using concordance index (C-index) and calibration curves. RESULTS: Out of 170 cases with complete follow-up, 87 received surgery/ablation and 12 received transplantation with significantly higher OS than chemotherapy alone while transplantation combined with chemotherapy showed better survival than solely transplantation. The combination of surgery and chemotherapy showed worse OS than surgery alone. Survival was negatively influenced by T4 stadium (HR = 5.91), while young age and surgery were positive predictive factors. There was no influence of gender, ethnicity or nodal status on survival. The rate of AFP positivity was comparable with and without the presence of distal metastases. CONCLUSION: FLC survival is greatly dependent upon appropriate surgical management irrespective of tumor stadium.

Immune-Mediated Diseases Associated With Cancer Risks.

IMPORTANCE: Immune regulation is important for carcinogenesis; however, the cancer risk profiles associated with immune-mediated diseases need further characterization. OBJECTIVE: To assess the prospective association of 48 immune-mediated diseases with the risk of total and individual cancers and the prospective association of organ-specific immune-mediated diseases with the risk of local and extralocal cancers. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used data from the UK Biobank cohort study on adults aged 37 to 73 years who were recruited at 22 assessment centers throughout the UK between January 1, 2006, and December 31, 2010, with follow-up through February 28, 2019. EXPOSURES: Immune-mediated diseases. MAIN OUTCOMES AND MEASURES: The association of immune-mediated diseases with risk of cancer was assessed with multivariable hazard ratios (HRs) and 95% CIs after adjusting for various potential confounders using time-varying Cox proportional hazards regression. Heterogeneity in the associations of organ-specific immune-mediated diseases with local and extralocal cancers was assessed using the contrast test method. RESULTS: A total of 478 753 participants (mean [SD] age, 56.4 [8.1] years; 54% female) were included in the study. During 4 600 460 person-years of follow-up, a total of 2834 cases of cancer were documented in 61 496 patients with immune-mediated diseases and 26 817 cases of cancer in 417 257 patients without any immune-mediated diseases (multivariable HR, 1.08; 95% CI, 1.04-1.12). Five of the organ-specific immune-mediated diseases were significantly associated with higher risk of local but not extralocal cancers: asthma (HR, 1.34; 95% CI, 1.14-1.56), celiac disease (HR, 6.89; 95% CI, 2.18-21.75), idiopathic thrombocytopenic purpura (HR, 6.94; 95% CI, 3.94-12.25), primary biliary cholangitis (HR, 42.12; 95% CI, 20.76-85.44), and autoimmune hepatitis (HR, 21.26; 95% CI, 6.79-66.61) (P < .002 for heterogeneity). Nine immune-mediated diseases were associated with an increased risk of cancers in the involved organs (eg, asthma with lung cancer [HR, 1.34; 95% CI, 1.14-1.57; P < .001] and celiac disease with small intestine cancer [HR, 6.89; 95% CI, 2.18-21.75; P = .001]); 13 immune-mediated diseases were associated with an increased risk of cancer in the near organs (eg, Crohn disease with liver cancer: [HR, 4.01; 95% CI, 1.65-9.72; P = .002]) or distant organs (eg, autoimmune hepatitis with tongue cancer [HR, 27.75; 95% CI, 3.82-199.91; P = .001]) or in different systems (eg, idiopathic thrombocytopenic purpura with liver cancer [HR, 11.96; 95% CI, 3.82-37.42; P < .001]). CONCLUSIONS AND RELEVANCE: In this cohort study, immune-mediated diseases were associated with an increased risk of total cancer. Organ-specific immune-mediated diseases had stronger associations with risk of local cancers than extralocal cancers. The associations for individual immune-mediated diseases were largely organ specific but were also observed for some cancers in the near and distant organs or different systems. Our findings support the role of local and systemic immunoregulation in cancer development.

Gallstone Disease and Risk of Conventional Adenomas and Serrated Polyps: A Prospective Study.

BACKGROUND: Gallstone disease has been associated with colorectal cancer and some form of polyps, although the findings are inconclusive. It remains unknown whether gallstone disease influences the initiation of colorectal cancer. METHODS: We prospectively assessed the association of gallstone disease with risk of colorectal cancer precursors, including conventional adenomas and serrated polyps, in the Nurses' Health Study (1992-2012), the Nurses' Health Study II (1991-2011), and the Health Professionals Follow-up Study (1992-2012). Gallstone diseases were assessed using biennial follow-up questionnaires. Self-reported polyp diagnosis was confirmed by review of medical records. Logistic regression models were used to calculate the ORs with adjustment for smoking and other potential confounders. RESULTS: Among participants who had undergone a total of 323,832 endoscopies, 16.5% had gallstone disease and 11.3% received cholecystectomy. We documented 1,724, 1,212, and 1,943 cases of conventional adenomas and 1,470, 1,090, and 1,643 serrated polyps in patients with gallstones, cholecystectomy, and either of them, respectively. The OR for adenomas was 1.00 [95% confidence interval (CI): 0.95-1.06] for gallstones, 0.99 (95% CI, 0.93-1.06) for cholecystectomy, and 1.00 (95% CI, 0.95-1.05) for either exposure. The corresponding ORs for serrated polyps were 0.98 (95% CI, 0.92-1.04), 0.99 (95% CI, 0.93-1.06), and 0.97 (95% CI, 0.92-1.03), respectively. CONCLUSIONS: Gallstone disease is not associated with colorectal polyps. IMPACT: Patients with gallstones appear to have similar risk of colorectal polyps compared with those without and may therefore follow average-risk colorectal cancer screening guidelines.

Prospective study to evaluate the prognostic value of different nutritional assessment scores in liver surgery: NURIMAS Liver (DRKS00006340).

BACKGROUND: Malnutrition is recognised as a preoperative risk factor for patients undergoing hepatic resection. It is important to identify malnourished patients and take preventive therapeutic action before surgery. However, there is no evidence regarding which existing nutritional assessment score (NAS) is best suited to predict outcomes of liver surgery. METHODS: All patients scheduled for elective liver resection at the surgical department of the University Hospital of Heidelberg and the Municipal Hospital of Karlsruhe were screened for eligibility. Twelve NASs were calculated before operation, and patients were categorised according to each score as being either at risk or not at risk for malnutrition. The association of malnutrition according to each score and occurrence of at least one major complication was the primary endpoint, which was achieved using a multivariate logistic regression analysis including established risk factors in liver surgery as covariates. RESULTS: The population consisted of 182 patients. The percentage of patients deemed malnourished by the NAS varied among the different scores, with the lowest being 2.20% (Mini Nutritional Assessment) and the highest 52.20% (Nutritional Risk Classification). Forty patients (22.0%) had a major complication. None of the scores were significantly associated with major complications. CONCLUSIONS: None of the twelve investigated NAS defined a state of malnutrition that was independently associated with postoperative complications. Other means of measuring malnutrition in liver surgery should be investigated prospectively.