Search

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.

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 (P

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.

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.

BackgroundEvidence 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.ObjectiveWe generated a metabolite profile for adherence to MedDiet and evaluated its cross-sectional association with aspects of cognitive performance.MethodsA total of 1,250 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.ResultsWe 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.ConclusionsA 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.

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.

Georgios Polychronidis,1 Jincheng Feng,2 Anastasia Murtha-Lemekhova,1 Ulrike Heger,1 Arianeb Mehrabi,1 Katrin Hoffmann1 1Department of General, Visceral and Transplant Surgery, Heidelberg University Clinic, Heidelberg, Germany; 2Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Katrin HoffmannDepartment of General, Visceral and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 420, Heidelberg, 69120, GermanyEmail katrin.hoffmann@med.uni-heidelberg.deBackground: 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.Keywords: fibrolamellar, hepatocellular, carcinoma, SEER

Background: Individuals with polypectomy are still at higher risk of developing colorectal cancer than general population and are thus recommended to undergo colonoscopy surveillance for timely detection and prevention of subsequent colorectal cancer. The current clinical guidelines regarding the interval of surveillance are based on weak evidence. There is substantial overuse of surveillance colonoscopy in low-risk individuals and underuse in high-risk individuals. Effective risk stratification tools for post-polypectomy colorectal cancer (PPCRC) are lacking. Methods: Leveraging the integrated endoscopic, histopathologic and epidemiologic data in 3 population-based cohorts (Nurses’ Health Study (NHS) I, II and Health Professionals Follow-up Study (HPFS)), we developed a risk score to predict incident PPCRC among 26,744 patients with a polypectomy between 1986 and 2017. We validated the risk score in the Mass General Brigham (MGB) colonoscopy cohort of 76,603 individuals with a polypectomy between 2005 and 2017. In the MGB cohort, we used the validated natural language processing algorithms to extract detailed histopathologic data and merged them with the endoscopic and other clinical data from the electronic health record systems. The detailed protocol for the cohort development has been published (PMID: 33590405). We used Cox regression to calculate the hazard ratios (HRs) and assessed the discrimination using C-statistics and reclassification using the Net Reclassification Improvement (NRI). Results: During a median follow-up of 12.8 (IQR: 9.3, 16.7) and 5.1 (IQR: 2.7, 7.8) years in the NHS I, II/HPFS and MGB colonoscopy cohorts, we documented 220 and 241 PPCRC cases, respectively. We identified a PPCRC risk score based on 11 predictors. In the validation cohort, the risk score showed a strong association with higher risk of PPCRC (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 of patients (C-statistic, 0.73 and 0.71, respectively) defined by the current colonoscopy surveillance guidelines, leading to a NRI of 45% for PPCRC patients. Conclusion: We developed and validated a risk stratification model for PPCRC that can be used to guide tailored colonoscopy surveillance. Citation Format: Markus Dines Knudsen, Liang Wang, Kai Wang, Georgios Polychronidis, Paula Berstad, Kana Wu, Xiaosheng He, Dong Hang, Zhe Fang, Shuji Ogino, Andrew T. Chan, Edward L. Giovannucci, Molin Wang, Mingyang Song. Development and validation of a risk prediction model for post-polypectomy colorectal cancer in 4 prospective US cohorts [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr PR002.

Background: There is little population-based data on hepatocellular carcinoma (HCC) with brain metastases at initial diagnosis published. This study aimed to estimate incidence of brain metastases in initial metastatic HCC and its impact on prognosis.Methods: Newly diagnosed HCC cases from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were screened for the presence of brain metastases. Data were stratified by age and ethnicity. Multivariable logistic and Cox regression were used to identify factors associated with brain metastases and factors associated with overall survival (OS) and cancer-specific survival (CSS), respectively. Kaplan-Meier method and log-rank test were used for survival analysis.Results: 141 cases presenting with brain metastases were identified, accounting for 0.35% of all HCC cases and 2.37% of cases with metastatic HCC disease. The incidence rate was highest among cases with age 50-59 (2.74%), respectively. Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African American patients presented significantly lower disease-specific survival (median time: 1month; 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%CI 8.40-18.97), but not associated with worse OS and CSS among brain metastases cases. Conclusions: The study shows population-based incidence and survival of brain metastases at diagnosis of HCC. Brain metastases are most prevalent in initial metastatic HCC patients with lung or bone metastasis. The results may contribute to consider screening of the brain among HCC with initial lung or bone metastasis.

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

We read with great interest the study by Coker et al 1 that provided supportive evidence for the role of oral microbiota in gastric cancer. A few studies also highlighted the possible link with oesophageal cancer.2–4 However, there is a lack of robust epidemiologic data on whether periodontal disease and tooth loss, indicators of oral microbial dysbiosis, are associated with these two cancers. Here, we prospectively examined the association of history of periodontal disease and tooth loss with the risk of oesophageal and gastric adenocarcinoma in 98 459 women from the Nurses’ Health Study (1992–2014) and 49 685 men from the Health Professionals Follow-up Study (1988–2016). Dental measures, demographics, lifestyle, and diet were assessed using validated follow-up questionnaires. Self-reported cancer diagnosis was confirmed by review of medical records. We used Cox proportional hazards models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). We also examined the independent association of history of periodontal disease and tooth loss in a joint analysis. Over 22–28 years of follow-up, we documented 199 cases of oesophageal adenocarcinoma and 238 cases of gastric adenocarcinoma. History of periodontal disease was associated with a 43% and 52% increased risk of oesophageal adenocarcinoma (multivariable-adjusted HR (aHR) 1.43, 95% CI 1.05 to 1.96) and gastric adenocarcinoma (aHR 1.52, 95% CI 1.13 to 2.04) (table …

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.

SummaryPancreatic 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.

Background Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal neoplastic process, largely due to the presence of disseminated disease at presentation. As such, evidence-based management of metastatic disease is integral to patient care in such circumstances. This review aimed to summarize the current state of knowledge regarding the potential effectiveness of liver metastasectomy in the setting of PDAC. Methods A structured review of the literature was performed from April to May 2016, using the PubMed database. Relevant original research articles and systematic reviews/meta-analyses published between 1990 and 2015 were considered eligible. The primary endpoint was overall survival in patients undergoing resection for PDAC and liver metastasectomy. Studies reporting on fewer than 10 patients were excluded. Results Ultimately, eight studies met our inclusion criteria. Their results suggest that hepatic metastasectomy for PDAC is a safe procedure, with a potential survival benefit for carefully selected patients, particularly those with metachronous metastases. Nonetheless, small sample sizes and inconsistent use of appropriate controls preclude generalization of these findings. Conclusion Multi-institutional prospective studies are required to fully delineate the potential therapeutic utility and operative indications of liver metastasectomy in the setting of modern interdisciplinary management of PDAC.

Um eine Transplantatabstosung zu vermeiden, ist nach Organtransplantation eine Immunsuppression unumganglich – jedoch mit teils erheblichen Nebenwirkungen. Eine Kombinationstherapie kann die Nebenwirkungen begrenzen, ohne das Transplantat zu gefahrden.

Background: Tacrolimus-based immunosuppression has resulted in enormous improvements on liver transplantation (LTx) outcomes. However, dose adjustment and medication adherence play a key role in post-transplant treatment success. The aim of the present study is to assess the trough levels and the need for adaptation of therapeutic doses in de novo LTx patients treated with Tacrolimus in the clinical routine, without any intervention to the treatment regimen. Methods and analysis: This is a pilot, prospective, exploratory, monocentric, non-interventional and non-randomized investigator-initiated study. Prospectively maintained data of 100 patients treated with various oral Tacrolimus-based immunosuppressants (Prograf or Envarsus) will be analyzed. The number of required dose adjustments of Tacrolimus formulations used in clinical routine for achieving the target trough level, Tacrolimus trough level, Tacrolimus dosing, concentration/dose ratio, routine laboratory tests, efficacy data (incl. survival, acute rejection, re-transplantation), patients therapy adherence, and infections requiring the need to reduce individual immunosuppressant dosing will be evaluated for each patient. Result: This study will evaluate the trough levels and the need for adaptation of therapeutic doses in de novo LTx patients treated with Tacrolimus in the clinical routine, without any intervention to the treatment regimen. Conclusion: The HDTACRO study will be the first study to systematically and prospectively evaluate various oral Tacrolimus-based immunosuppressants in de novo liver transplanted patients. If a difference between the therapy-subgroups is evident at the end of the trial, a randomized control trial will eventually be designed. Registration number: ClinicalTrials.gov: NCT04444817.

Background Hand-assisted laparoscopic living donor nephrectomy (HALDN) using a periumbilical or Pfannenstiel incision was developed to improve donor outcome after a kidney transplant. The aim of this study was to investigate two methods of hand assistance and kidney removal during HALDN and their effect on the time it takes for the donor to return to normal physical activity. Methods/design This study was initiated in November 2017 and is expected to last for 2 years. To be eligible for the study, donors must be more than 20 years of age and must not be receiving permanent pain therapy. Only donors with a single artery and vein in the graft are being enrolled in this trial. Donors with infections or scars in the periumbilical or hypogastric area, bleeding disorders, chronic use of immunosuppressive agents, or active infection will be excluded. Donors will be randomly allocated to either a control arm (periumbilical incision) or an intervention arm (Pfannenstiel incision). The sample size was calculated as 26 organ donors in each group. The primary endpoint is the number of days it takes the donor to return to normal physical activity (up to 4 weeks after the operation). Secondary endpoints are intraoperative outcomes, including estimated blood loss, warm ischemia time, and duration of the operation. Postoperative pain will be assessed using the visual analog scale, rescue analgesic use, and peak expiratory flow rate. Length of hospital stay, physical activity score, time to return to work, donor satisfaction, cosmetic score, postoperative complications, and all-cause mortality in living donors will also be reported. Delayed graft function, primary non-function, serum creatinine levels, and glomerular filtration rate will also be assessed in the recipients after transplantation. Discussion This is the first randomized controlled trial to compare the time it takes the living donor to return to normal physical activity after HALDN using two different types of incision. The comprehensive findings of this study will help decide which nephrectomy procedure is best for living donors with regard to patient comfort and satisfaction as well as graft function in the recipient after transplantation. Trial registration ClinicalTrials.gov, NCT03317184. Registered on 23 October 2017. Electronic supplementary material The online version of this article (10.1186/s13063-018-2775-4) contains supplementary material, which is available to authorized users.

Background The objective of this study was to investigate the potential benefit of local haemostatic agents for the prevention of postoperative bleeding after thyroidectomy. Methods A systematic literature search was performed, and RCTs involving adult patients who underwent thyroid surgery using either active (AHA) or passive (PHA) haemostatic agents were included in the review. The main outcome was the rate of cervical haematoma that required reoperation. A Bayesian random-effects model was used for network meta-analysis with minimally informative prior distributions. Results Thirteen RCTs were included. The rate of cervical haematoma requiring reoperation ranged from 0 to 9·1 per cent, and was not reduced by haemostatic agents: AHA versus control (odds ratio (OR) 1·53, 95 per cent credibility interval 0·21 to 10·77); PHA versus control (OR 2·74, 0·41 to 16·62) and AHA versus PHA (OR 1·77, 0·12 to 25·06). No difference was observed in the time required for drain removal, duration of hospital stay, and the rate of postoperative hypocalcaemia or recurrent nerve palsy. AHA led to a significantly lower total postoperative blood loss and reduced operating time in comparison with both the control and PHA groups. Conclusion The general use of local haemostatic agents has not been shown to reduce the rate of clinically relevant bleeding.

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.

The maximal liver function capacity (LiMAx) test, a novel

Background Margin status with resection of colorectal liver metastasis (CRLM) was an important prognostic factor in the years before the introduction of biological chemotherapy. This study examined outcomes following CRLM resection in patients who received neoadjuvant chemotherapy with or without the monoclonal antiangiogenic antibody bevacizumab. Methods Patients who underwent surgery for CRLM at the Johns Hopkins Hospital between 2000 and 2015 were identified from an institutional database. Data regarding surgical margin status, preoperative bevacizumab administration and overall survival (OS) were assessed using multivariable analyses. Results Of 630 patients who underwent CRLM resection, 417 (66·2 per cent) received neoadjuvant chemotherapy with (214, 34·0 per cent) or without (203, 32·2 per cent) bevacizumab. The remaining 213 (33·8 per cent) did not receive neoadjuvant chemotherapy. Univariable analysis found that positive margins were associated with worse 5-year OS than R0 resection (36·2 versus 54·9 per cent; P = 0·005). After dichotomizing by the receipt of preoperative bevacizumab versus chemotherapy alone, the prognostic value of pathological margin persisted among patients who did not receive preoperative bevacizumab (5-year OS 53·0 versus 37 per cent after R0versus R1 resection; P = 0·010). OS was not significantly associated with margin status in bevacizumab-treated patients (5-year OS 46·8 versus 33 per cent after R0versus R1 resection; P = 0·081), in whom 5-year survival was slightly worse (presumably reflecting more advanced disease) than among patients treated with cytotoxic agents alone. Pathological margin status was not significantly associated with 5-year OS in patients with a complete or near-complete response to chemotherapy and bevacizumab (43 versus 30 per cent after R0versus R1 resection; P = 0·917), but this may be due to a type II error. Conclusion The impact of margin status varied according to the receipt of bevacizumab. Bevacizumab may have a role to play in improving outcomes among patients with more advanced disease.

Pancreatic ductal adenocarcinoma (PDAC) is an extremely lethal neoplastic process, largely due to the presence of disseminated disease at presentation. As such, evidence-based management of metastatic disease is integral to patient care in such circumstances. This review aimed to summarize the current state of knowledge regarding the potential effectiveness of liver metastasectomy in the setting of PDAC.A structured review of the literature was performed from April to May 2016, using the PubMed database. Relevant original research articles and systematic reviews/meta-analyses published between 1990 and 2015 were considered eligible. The primary endpoint was overall survival in patients undergoing resection for PDAC and liver metastasectomy. Studies reporting on fewer than 10 patients were excluded.Ultimately, eight studies met our inclusion criteria. Their results suggest that hepatic metastasectomy for PDAC is a safe procedure, with a potential survival benefit for carefully selected patients, particularly those with metachronous metastases. Nonetheless, small sample sizes and inconsistent use of appropriate controls preclude generalization of these findings.Multi-institutional prospective studies are required to fully delineate the potential therapeutic utility and operative indications of liver metastasectomy in the setting of modern interdisciplinary management of PDAC.

The maximal liver function capacity (LiMAx) test, a novel 13C-methacetin breath test, has proven clinical validity in determining hepatic metabolic capacity. In contrast to prior 13C-methacetin breath test protocols, the LiMAx test is performed by intravenous body-weight-adjusted substrate administration. Furthermore, the DOB kinetics (delta over baseline of the time-dependent exhaled 13CO2/12CO2 ratio) are measured online at the bedside with a high time resolution in order to determine the maximum DOB. The aim of this study was to analyze the recorded DOB kinetics in a large population for further refinement of the test protocol. Two new methods of kinetic analysis are proposed in this article: the time dependency of the DOB kinetics and the time interval until half of the DOB maximum. A total of 10 100 LiMAx tests on 8483 patients performed during routine clinics at eight centers were available. The kinetic analysis revealed a specific pattern of DOB kinetics depending upon LiMAx result. In addition, potential co-factors for DOB kinetics, such as weight, height, gender and age, were analyzed, yielding a potential influence of gender and smoking behavior. Both the specific patterns and the proposed kinetic analysis have the potential to further improve the sensitivity and specificity of the test and its clinical applicability by shortening its duration.