Diverticulitis Is Associated with Increased Risk of Colon Cancer-A Nationwide Register-Based Cohort Study.

Background: An association between diverticulitis and colon cancer has been proposed. The evidence is conflicting, and the guidelines differ regarding recommended follow-up with colonoscopy after an episode of diverticulitis. To guide regimes for follow-up, this study aimed to investigate if patients with diverticulitis have an increased risk of colon cancer. Methods: This study is reported according to the RECORD statement. We performed a cohort study with linked data from nationwide Danish registers. The inclusion period was 1997-2009, and the complete study period was 1995-2013. The primary outcome was the risk of developing colon cancer estimated using a Cox regression analysis with time-varying covariates. We performed a sensitivity analysis on a cohort of people with prior colonoscopies, comparing the risk of colon cancer between the diverticulitis group and the control group. Results: We included 29,173 adult males and females with diverticulitis and 145,865 controls matched for sex and age. The incidence proportion of colon cancer was 2.1% (95% confidence interval (CI) 1.9-2.3) in the diverticulitis group and 1.5% (95% CI 1.4-1.5) in the matched control group (hazard ratio 1.6; 95% CI 1.5-1.8). The risk of having a colon cancer diagnosis was significantly increased in the first six months after inclusion (hazard ratio 1.7; 95% CI 1.5-1.8), and hereafter there was a lower risk in the diverticulitis group compared with controls (hazard ratio 0.8; 95% CI 0.7-0.9). This protective effect lasted eight years. The increased risk of colon cancer during the first six months after diverticulitis was also found in the cohort with prior colonoscopies. Conclusions: The risk of a colon cancer diagnosis was significantly increased for patients with diverticulitis 0-6 months after the diagnosis of diverticulitis. Hereafter, we found a protective effect of diverticulitis until eight years later, possibly due to a screening effect. We recommend a follow-up colonoscopy after the first diagnosis of diverticulitis.

Technique efficacy and complications after ablation as first surgical intervention for hepatocellular carcinoma: A nationwide database study.

INTRODUCTION: Despite limited evidence, technique efficacy and complications may be important short-term outcomes after ablation for hepatocellular carcinoma (HCC). We aimed to report these outcomes after ablation as the first surgical intervention for HCC. METHODS: This nationwide cohort study was based on data from the Danish Liver and Biliary Duct Cancer Database and medical records. Variables associated with outcomes were investigated using logistic regression. RESULTS: From 2013 to 2023, 433 patients were included of which 79% were male, 73% had one tumor, and 90% had cirrhosis. Complete ablation was achieved after percutaneous, laparoscopic, and open approach in 84%, 100%, and 96% of the procedures, respectively. Most patients did not experience complications (76%). Open ablation compared with percutaneous was associated with higher risk of complications in multivariable adjusted analysis (Clavien-Dindo grade 2-5 (odds ratio 5.34, 95% confidence interval [2.36; 12.08]) and 3B-5 (5.70, [2.03; 16.01]), and lower risk of incomplete ablation (0.19 [0.05; 0.65]). Number of tumors ≥3 was associated with a higher risk of incomplete ablation (3.88, [1.45; 10.41]). Tumor diameter ≥3 cm was associated with increased risk of complications grade 2-5 (2.84, [1.29; 6.26]) and 3B-5 (4.44, [1.62; 12.13]). Performance status ≥2 was associated with risk of complications grade 3B-5 (5.98, [1.58; 22.69]). Tumor diameter was not associated with technique efficacy. CONCLUSION: Open ablation had a higher rate of complete ablation compared with percutaneous but was associated with a higher risk of complications. Tumor diameter ≥3 cm and performance status ≥2 were associated with a higher risk of complications.

Prognostic genomic alterations in patients undergoing liver resection for hepatocellular carcinoma.

INTRODUCTION: Genetic mutations and amplifications found in hepatocellular carcinoma (HCC) have a potentially prognostic impact. The aim of this study was to investigate the prognostic value of mutations and amplifications in HCC from patients that were liver resected. METHODS: Patients liver resected for HCC at Copenhagen University Hospital Rigshospitalet between May 2014 and January 2018 were included. DNA from freshly frozen tumour tissue was investigated with TruSight Oncology 500. Mutations and amplifications were correlated with disease-free survival and overall survival using multivariate Cox regression to assess the effect on prognosis. RESULTS: Of the 51 patients included, 88% were male and the median age was 69 years. Most patients had a single tumour (84%) with no vascular invasion (67%) in a non-cirrhotic liver (76% with fibrosis, 24% with cirrhosis). The median follow-up was 37 months. Patients with a MYC amplification (8%) were significantly younger than the remaining patients. Furthermore, they had a significantly shorter overall survival (15 months (95% CI: 0.0-31.6) vs. 59 months (95% CI: 34.4-83.6), p = < 0.001) and disease-free survival (8 months (95% CI: 4.6-11.4) vs. 19 months (95% CI: 12.3-25.7), p = 0.03). However, only overall survival remained statistically significant in the adjusted analysis. Furthermore, all patients with an ARID1A mutation (6%) had microvascular invasion and significantly larger tumours than the patients without ARID1A mutation. CONCLUSION: MYC amplifications had a prognostic influence on survival, whereas ARID1A gene mutations were correlated with microvascular invasion. These may serve as prognostic biomarkers and should be validated in large, independent cohort.

Early Results of a Screening Program for Skin Cancer in Liver Transplant Recipients: A Cohort Study.

(1) Background: Skin cancer is the most common cancer in transplant recipients. Timely and regular screening may reduce advanced disease. The study aimed to determine referral rates to screening, the incidence, and risk factors of skin cancer in a Danish liver transplant recipient cohort. (2) Methods: All first-time liver transplant recipients, >18 years old, attending outpatient care between January 2018 and December 2021 were included. The referral rates and incidence of skin cancer/preneoplastic lesions were calculated. Risk factors were assessed using Cox regression analyses. (3) Results: Of the 246 included recipients, 219 (89.0%) were referred to screening, and 102 skin cancer/preneoplastic lesions were diagnosed in 32 (15.6%) recipients. The IR of any skin cancer/preneoplastic lesion was 103.2 per 1000 person-years. BCC was the most frequent skin cancer followed by SCC, IR: 51.3 vs. 27.1 per 1000 person-years, respectively. No cases of MM were observed. The IR of actinic keratosis and Bowen's Disease were 48.1 vs. 13.2 per 1000 person-years, respectively. Time since transplantation was independently associated with skin cancer/preneoplastic lesions, HR (95%CI) 2.81 (1.64-4.80). (4) Conclusions: The study determined the incidence and risk factors of skin cancer/preneoplastic lesions in liver transplant recipients enrolled in a screening program, while demonstrating a high screening referral rate.

Fraction of exhaled nitric oxide is higher in liver transplant recipients than in controls from the general population: a cohort study.

Background: Fraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population. Methods: FENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders. Results: The median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46-64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10-26) vs. 13 ppb (IQR 8-18.), p < 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p < 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50-5.15, p < 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37-7.20, p = 0.007)]. Conclusion: The liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation.

Psychiatric and Educational Aspects of Familial Adenomatous Polyposis: A Nationwide Danish Cohort Study With Matched Nonexposed Individuals.

INTRODUCTION: Familial adenomatous polyposis (FAP) is an autosomal, dominantly inherited disorder that predisposes to colorectal cancer. An increased risk of cancer may affect mental health, but the magnitude of this effect remains unknown. We assessed the psychosocial functioning, including the educational level attained and risk of psychiatric comorbidity, of patients with FAP by comparing them with matched nonexposed individuals. METHODS: All Danish patients with FAP diagnosed before April 2021 were identified in the Danish Polyposis Register and paired with 4 matched nonexposed individuals. Educational history, psychiatric contacts or diagnoses ( International Classification of Disease, 10th Revision ), and treatment with antidepressants, anxiolytics, or antipsychotics were compared between patients with FAP and nonexposed individuals. RESULTS: The analysis included 445 patients with FAP and 1,538 nonexposed individuals. The highest educational level reached was significantly lower for patients with FAP ( P < 0.001). When comparing patients with FAP and nonexposed and adjusting for a cancer diagnosis, an increased risk was observed for a psychiatric contact (1.69, 95% confidence interval [CI] 1.25-2.29, P < 0.001), any psychiatric prescription (1.39, 95% CI 1.17-1.66, P < 0.001), a psychiatric diagnosis (1.64, 95% CI 1.19-2.26, P = 0.002), and experiencing any psychiatric event (hazard ratio 1.42, 95% CI 1.20-1.68, P < 0.001). An increased risk was specifically seen for mood (affective) disorders (1.76, 95% CI 1.09-2.83, P = 0.02) and behavioral and emotional disorders (2.01, 95% CI 1.10-3.69, P = 0.02) and the need for antidepressants (1.59, 95% CI 1.24-2.03, P < 0.001) and antipsychotics (1.85, 95% CI 1.26-2.70, P = 0.002). DISCUSSION: Compared with nonexposed individuals, patients with had significantly less education and an increased risk of developing mood and behavioral disorders, with an increased likelihood of needing antidepressants and antipsychotics.

Ablation therapy for patients with colorectal liver metastases with and without extrahepatic metastases: evaluation of long-term outcomes and prognostic factors.

PURPOSE: Ablation is a valuable treatment alternative to surgery for colorectal liver metastases. This study reports the long-term clinical outcomes in patients treated with ablation for colorectal liver metastases with or without extrahepatic metastases. METHODS: Patients with colorectal liver metastases treated with ultrasound-guided ablation at Herlev Hospital, Denmark were included in this retrospective study. RESULTS: This study included 284 patients with 582 metastases. Complete ablation was obtained in 258 patients (91%) evaluated within 6 weeks. During follow-up, 94 patients (33%) developed local recurrence. The median survival for all patients was 31 months, with 1-, 3-, and 5-year survival rates of 82%, 45%, and 21%, respectively. The median survival for patients with extrahepatic metastases (n=49, 17%) was 24 months compared with 33 months for patients without (P=0.142). Propensity score-adjusted Cox regression showed that extrahepatic metastases were associated with increased mortality, with a hazard ratio (HR) of 1.45 (95% confidence interval [CI], 1.02 to 2.05; P=0.039). In multivariate Cox regression analysis for all patients, increased mortality risk was found for a diameter ≥2.6 cm (HR, 1.59; 95% CI, 1.23 to 2.05), >1 metastasis (HR, 1.66; 95% CI, 1.28 to 2.16), and extrahepatic metastases (HR, 1.45; 95% CI, 1.04 to 2.03). Male sex (HR, 0.75; 95% CI, 0.58 to 0.98) and receiving chemotherapy (HR, 0.69; 95% CI, 0.52 to 0.92) were associated with decreased mortality. CONCLUSION: Ablation for colorectal liver metastases offers acceptable survival rates, including for patients with extrahepatic metastases. In addition, chemotherapy was associated with improved survival for both patients with and without extrahepatic metastases.

Cancer in Patients With Familial Adenomatous Polyposis: A Nationwide Danish Cohort Study With Matched Controls.

BACKGROUND & AIMS: Familial adenomatous polyposis (FAP) is a hereditary disorder that predisposes patients to colorectal cancer (CRC). Prophylactic colectomy has greatly reduced the risk of CRC. However, new associations between FAP and the risk of other cancers have subsequently emerged. In this study, we assessed the risk of specific primary and secondary cancers among patients with FAP compared with matched controls. METHODS: All known patients with FAP up until April 2021 were identified in the nationwide Danish Polyposis Register and paired with 4 unique controls matched by birth year, sex, and postal code. The risk of overall cancers, specific cancer types, and risk of a second primary cancer was assessed and compared with controls. RESULTS: The analysis included 565 patients with FAP and 1890 controls. The overall risk of cancer was significantly higher for patients with FAP than for controls (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.28-5.17; P < .001). The increased risk was mainly due to CRC (HR, 4.61; 95% CI, 2.58-8.22; P < .001), pancreatic cancer (HR, 6.45; 95% CI, 2.02-20.64; P = .002), and duodenal/small-bowel cancer (HR, 14.49; 95% CI, 1.76-119.47; P = .013), whereas no significant difference was observed for gastric cancer (HR, 3.29; 95% CI, 0.53-20.23; P = .20). Furthermore, the risk of a second primary cancer was significantly higher for patients with FAP (HR, 1.89; 95% CI, 1.02-3.50; P = .042). Between 1980 and 2020, the risk of cancer among patients with FAP decreased by ∼50%. CONCLUSIONS: Despite an absolute reduction in the risk of developing cancer among patients with FAP, the risk remained significantly higher than for the background population due to colorectal, pancreatic, and duodenal/small-bowel cancers.

Characteristics of de novo cancer in liver transplant recipients.

Liver transplant recipients receive immunosuppressive treatment to avoid organ rejection, increasing the risk of developing de novo cancer after transplantation. We investigated the cumulative incidence of de novo cancer in a cohort of Danish liver transplant recipients. The study was a retrospective cohort study of adult liver transplant recipients transplanted at Rigshospitalet, Copenhagen, Denmark, between January 1, 2010, and December 31, 2019. De novo cancer was defined as cancer arising at least 30 days after liver transplantation, excluding relapses from prior cancers and donor-derived cancers. We determined the incidence of de novo cancer in the cohort using the Aalen-Johansen estimator, with death and retransplantation as competing risks. We included 389 liver transplant recipients and identified 47 recipients (12%) with de novo cancer after liver transplantation, including 25 recipients with non-melanoma skin cancers. The cumulative incidences at 5 years after liver transplantation for all cancers and non-skin cancers were 10.7% and 4.9%, respectively. De novo cancer after liver transplantation is relatively common, with the majority being non-melanoma skin cancer. Future studies of sufficient size are needed to identify risk factors for de novo cancer after liver transplantation.

Surgery in Patients with Gastro-Entero-Pancreatic Neuroendocrine Carcinomas, Neuroendocrine Tumors G3 and High Grade Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.

OPINION STATEMENT: In the 2019 WHO guidelines, the classification of gastro-entero-pancreatic neuroendocrine neoplasms (GEP NEN) has changed from one being based on Ki-67 proliferation index alone to one that also includes tumor differentiation. Consequently, GEP NENs are now classified as well-differentiated neuroendocrine tumor (NET), NET G1 (Ki-67 <3%), NET G2 (Ki-67 3-20%) and NET G3 (Ki-67 >20%), and poorly differentiated neuroendocrine carcinoma (NEC) (Ki-67 >20%). It has been suggested that NET G3 should be treated as NET G2 with respect to surgery, while surgical management of NEC should be expanded from local disease to also include patients with advanced disease where curative surgery is possible. High grade mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) have a neuroendocrine and a non-neuroendocrine component mostly with a poor prognosis. All studies evaluating the effect of surgery in NEC and MiNEN are observational and hold a risk of selection bias, which may overestimate the beneficial effect of surgery. Further, only a few studies on the effect of surgery in MiNEN exist. This review aims to summarize the data on the outcome of surgery in patients with GEP NET G3, GEP NEC and high grade MiNEN. The current evidence suggests that patients with NEN G3 and localized disease and NEN G3 patients with metastatic disease where curative surgery can be achieved may benefit from surgery. In patients with MiNEN, it is currently not possible to evaluate on the potential beneficial effect of surgery due to the low number of studies.

Aldehyde dehydrogenase expression may be a prognostic biomarker and associated with liver cirrhosis in patients resected for hepatocellular carcinoma.

BACKGROUND: Several members of the aldehyde dehydrogenase (ALDH) isoenzyme family have been suggested as prognostic biomarkers in patients with hepatocellular carcinoma (HCC). The aim of the study was to evaluate overall ALDH family member expression by RNA sequencing and hierarchical clustering in tumor and adjacent liver tissue to predict survival and evaluate correlation with liver cirrhosis in patients undergoing liver resection for HCC. METHODS: We included patients having undergone liver resection for HCC between May 2014 and January 2018 at a tertiary referral university hospital (Copenhagen University Hospital, Rigshospitalet, Denmark). ALDH family member expression was evaluated by RNA sequencing of tumor and non-tumor liver tissue. Hierarchical clustering of ALDH genes was used to identify patient groups and correlations were established with overall survival, recurrence and histological features. RESULTS: Fifty-two patients were included with 88.5% males, 84.6% with only one HCC and 73.1% with a non-cirrhotic background liver. Median follow-up was 45.7 months. Patients in one cluster defined by its ALDH expression in the tumor tissue showed significantly worse overall survival (log-rank p = 0.015), also when adjusted for age, cirrhosis, microvascular invasion, resection margins and tumor number (hazard ratio 4.2, 95% confidence interval (CI) 1.5-11.9, p = 0.007). When evaluated individually, the isoenzyme ALDH1L1 may be of particular importance. Several clusters in non-tumor tissue were correlated with cirrhosis. Especially one cluster had a high discriminative ability (area under receiver operating characteristic curve of 0.839) and remained significantly associated with cirrhosis when corrected for age, microvascular invasion, resection margins and tumor number (odds ratio 44.2, 95% CI 5.5-352.0, p < 0.001). The combination of ALDH and a previously identified candidate biomarker (expression signature of the transcriptional targets of the peroxisome proliferator-activated receptors (PPARs)) may add additional prognostic value. CONCLUSION: The expression of ALDH family members in HCC was correlated with overall survival. Moreover, ALDH expression in non-tumor liver tissue was correlated with cirrhosis. Members of the ALDH family of enzymes may serve as a prognostic biomarker as well as potential targets for systemic treatment.

Validation of the Endoscopic Part of the Spigelman Classification for Evaluating Duodenal Adenomatosis in Familial Adenomatous Polyposis: A Prospective Study of Interrater and Intrarater Reliability.

INTRODUCTION: In patients with familial adenomatous polyposis, the Spigelman classification is recommended for staging and risk stratification of duodenal adenomatosis. Although the classification has been used for decades, it has never been formally validated. METHODS: We included consecutive FAP patients undergoing upper gastrointestinal endoscopic surveillance and evaluated the inter- and intrarater reliability of the Spigelman classification. RESULTS: The interrater reliability of the endoscopic parameters and the Spigelman classification was good and excellent, respectively. The intrarater reliability of the endoscopic parameters and the Spigelman classification was moderate and good, respectively. DISCUSSION: The results support continued use of the Spigelman classification as the primary end point for future studies and as key endoscopic performance measure.

Morbidity and mortality after liver surgery for colorectal liver metastases: a cohort study in a high-volume fast-track programme.

BACKGROUND: For colorectal liver metastases, surgery is a high-risk procedure due to perioperative morbidity. The objective was to assess severity of complications after fast-track liver surgery for colorectal liver metastases and their impact on morbidity and mortality. METHODS: All patients were treated according to the same fast-track programme. Complications were graded according to the Clavien-Dindo classification for patients undergoing surgery from 2013 to 2015. Correlation between complications and length of stay was analysed by multivariate linear regression. RESULTS: 564 patient cases were included of which three patients died within 3 months (0.53%, 95% CI: 0.17-1.64%). Complications were common with Grade ≤ 2 in 167 patients (30%) and ≥ Grade 3a in 93 (16%). Patients without complications had a mean length of stay of 4.1 days, which increased with complications: 1.4 days (95% CI: 1.3-1.5) for Grade 2, 1.7 days (1.5-2.0) for Grade 3a, 2.3 days (1.7-3.0) for Grade 3b, 2.6 days (1.6-4.2) for Grade 4a, and 2.9 days (2.8-3.1) for Grade 4b. Following were associated with increased length of stay: complication severity grade, liver insufficiency, ascites, biliary, cardiopulmonary, and infectious complications. CONCLUSIONS: Complications after liver surgery for colorectal liver metastases, in a fast track setting, were associated with low mortality, and even severe complications only prolonged length of stay to a minor degree.

Surgery of the primary tumour in 201 patients with high-grade gastroenteropancreatic neuroendocrine and mixed neuroendocrine-non-neuroendocrine neoplasms.

The benefit of surgery in high-grade gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is uncertain. The present study aimed to investigate outcomes after tumour surgery in patients with high-grade (Ki-67 > 20%) GEP NEN or MiNEN stage I-III or stage IV. We analysed data from patients treated in the period 2007-2015 at eight Nordic university hospitals. Overall survival (OS) and progression-free survival (PFS)/disease-free survival (DFS) were analysed by Kaplan-Meier estimates. Prognostic factors were evaluated using Cox regression. We included 201 surgically resected patients, 143 stage I-III and 58 stage IV, with 68% having neuroendocrine carcinoma, 23% MiNEN, 5% neuroendocrine tumour G3 and 4% uncertain NEN G3. Primary tumours were located in colon/rectum (52%), oesophagus/cardia (19%), pancreas (10%), stomach (7%), jejunum/ileum (5%), duodenum (4%), gallbladder (2%) and anal canal (1%). For patients with stage I-III, median DFS was 12 months (95% confidence interval [CI] = 5.5-18.5) and median OS was 32 months (95% CI = 24.0-40.0). For patients with stage I-III and an R0 resection, median DFS was 21 months (95% CI = 4.9-37.1) and median OS was 39 months (95% CI = 25.0-53.0). For patients with stage IV, median PFS/DFS was 4 months (95% CI = 1.9-6.1) and median OS was 11 months (95% CI = 4.8-17.2). For patients with stage IV and an R0 resection, median DFS was 6 months (95% CI = 0-16.4) and median OS was 32 months (95% CI = 25.5-38.5). Performance status > 1 and colorectal primary were associated with poor prognosis. There was no difference in survival between patients with high-grade GEP NEN and MiNEN. Surgery of the primary tumour in patients with loco-regional high-grade GEP NEN or MiNEN led to good long-term results and should be considered if an R0 resection is considered achievable. Highly selected patients with stage IV disease may also benefit from surgery.

Peroxisome proliferator-activated receptor activity correlates with poor survival in patients resected for hepatocellular carcinoma.

BACKGROUND/PURPOSE: Few clinically useful biomarkers are known to predict prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between PPAR activity and ALDH7A1 expression and their prognostic significance using RNA sequencing in patients undergoing liver resection for HCC. METHODS: We included patients undergoing liver resection for HCC at a tertiary referral center for hepato-pancreato-biliary surgery between May 2014 and January 2018. PPAR activity and ALDH7A1 expression were evaluated by RNA sequencing and correlated with overall survival, recurrence and histological features. RESULTS: We included 52 patients with a median follow-up of 20.9 months, predominantly males (88.5%) with a single tumor (84.6%) in a non-cirrhotic liver (73.1%). Three-year overall survival was 48.6% in patients with a specific PPAR target gene expression profile (cancer cluster 3) compared with 81.7% in controls (P = .04, Log-rank test). This remained significant (odds ratio 14.02, 95% confidence interval 1.92-102.22, P = .009) when adjusted for age, cirrhosis, microvascular invasion, number of tumors and free resection margins. ALDH7A1 expression was not correlated with PPAR or any outcomes. CONCLUSION: PPAR activity in a subset of tumor samples was associated with reduced overall survival indicating that PPAR may be a valuable prognostic biomarker.

Model for end-stage liver disease score predicts complications after liver transplantation.

PURPOSE: Increased model for end-stage liver disease (MELD) score measured in the early postoperative course is associated with one-year mortality and graft loss. However, the correlation with postoperative complications has not been investigated. The aim of this study was to investigate the association between postoperative MELD score and subsequent complications. METHODS: Adult liver transplant recipients transplanted from January 2011 until December 2016 were included. MELD score days 1-5 were correlated with complications day 6-30, subdivided into type and severity according to Clavien-Dindo classification. RESULTS: We included 246 adult liver transplant recipients. Between days 6 and 30, 671 complications occurred in 201 of the patients (82%) corresponding to 64% of all postoperative complications in the whole postoperative period (days 0-30). In multivariate analyses adjusted for recipient gender and age, preoperative MELD score, and Eurotransplant Donor Risk Index, postoperative MELD score was significantly associated with having one or more complications, any type of complication except cardiovascular and renal complications, and complication severity. CONCLUSIONS: Postoperative MELD score days 1-5 were associated with complications arising in the subsequent period 6-30 days after transplantation. An increased MELD score should heighten the clinician's awareness of a possible complication.

Mortality after Transplantation for Hepatocellular Carcinoma: A Study from the European Liver Transplant Registry.

Background and Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients. Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding. Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23-1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99-1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21-3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31-2.00). Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables.

Readmission and reoperation rates following negative diagnostic laparoscopy for clinically suspected appendicitis: The "normal" appendix should not be removed - A retrospective cohort study.

BACKGROUND: In cases with clinically suspected appendicitis, there is controversy regarding the decision to remove a macroscopically normal appearing appendix during laparoscopy when no other intra-abdominal pathology is found. The aim of this study was to examine the rate of appendicitis, along with readmission and reoperation rates following diagnostic laparoscopy of clinically suspected appendicitis in patients where the appendix was not removed. METHODS: We performed a retrospective cohort analysis of patients who underwent a diagnostic laparoscopy due to clinical suspicion of appendicitis where no other pathology was found and the appendix was not removed. The study period was from 2008 to 2013 and involved patients from two university hospitals in the Copenhagen area. RESULTS: Of the 271 patients included (81.6% women, median age 27), 56 (20.7%) were readmitted with right iliac fossa pain after a median time of 10 months (range 1-84). Twenty-two patients (8.1%) underwent a new laparoscopic procedure. Appendix was removed in 18 patients, of which only one showed histological signs of inflammation. The median follow-up time was 5.6 years (range 1-109 months). CONCLUSION: There was a low rate of appendicitis after a previous negative diagnostic laparoscopy. Therefore, based on results from the current study, we do not consider that it is necessary to remove a macroscopic normal appendix during laparoscopy for clinically suspected appendicitis. The high readmission rate warrants the need for further investigation or follow-up.