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.

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.

Cancer Risks in Attenuated and Classical Familial Adenomatous Polyposis: A Nationwide Cohort with Matched, Non-Exposed Individuals: Cancer and surgery in AFAP and FAP patients.

INTRODUCTION: Familial adenomatous polyposis (FAP) is caused by pathogenic variants in the APC gene. FAP is usually categorized according to phenotype: classical FAP (CFAP) and attenuated FAP (AFAP); the latter is considered to have a milder disease course. We aimed to assess the risk of overall and specific cancers in CFAP and AFAP patients compared to matched, non-exposed individuals. METHODS: All known Danish FAP patients were classified as either CFAP or AFAP and assigned four matched, non-exposed individuals. The risk of overall and specific cancers, and mortality were analyzed. RESULTS: The analysis included 311 CFAP patients, 134 AFAP patients, and 1,600 non-exposed individuals. The overall cancer risk was significantly higher for both CFAP and AFAP patients than for non-exposed individuals, with hazard ratios (HR) of 4.77 (95% confidence interval (CI), 3.61-6.32; P<0.001) for CFAP and 3.22 (95% CI, 2.16-4.80; P<0.001) for AFAP. No significant difference was observed when comparing CFAP and AFAP (HR=1.48; 95% CI, 0.98-2.25; P=0.0646). The HR of colonic cancer was 2.16 (95% CI, 0.99-7.72; P=0.0522) and 2.72 (95% CI, 1.19-6.22; P=0.0177 for CFAP and AFAP), respectively compared to non-exposed and did not differ between CFAP and AFAP patients (HR=0.80; 95% CI, 0.32-2.00; P=0.6278). Mortality was significantly higher in CFAP (HR=2.96; 95% CI, 2.04-4.28; P<0.001), but not in AFAP (HR=1.40; 95% CI, 0.73-2.69; P=0.311). CONCLUSION: Nationwide data reveal differing risk profiles for specific cancers and mortality in AFAP and CFAP compared to non-exposed individuals. The cancer burden of AFAP necessitates consistent monitoring of these patients.

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.

Laparoscopic ablation for liver malignancies: initial experience at a Scandinavian high volume HPB center.

BACKGROUND: Ablation is an effective, parenchymal-sparing treatment for primary liver cancer and liver metastases. The purpose of this study was to report our initial experience with laparoscopic microwave ablation regarding postoperative complications, rate of conversions to open procedure, and technical efficacy. METHODS: This was a quality improvement project carried out at a tertiary care center in Denmark. Patients ≥ 18 years old with liver malignancies, not available for percutaneous ablation, and treated with ultrasound-guided laparoscopic ablation were included. RESULTS: From March 2023 to December 2023, 39 patients were referred for laparoscopic ablation after a multidisciplinary team conference. Of these, two procedures were converted to open procedures due to adhesion and tumor progression. Three patients rejected the sharing of medical information, two procedures were canceled and in one case the strategy was changed perioperatively. Therefore, 32 procedures in 31 patients were available for analysis. Complete ablation was evaluated after 1 month and was achieved in 100% of the procedures. None of the patients died, and no complications were reported in 21 cases (65.6%). Most patients with complications had a grade 1 complication based on the Clavien-Dindo classification, which among others included abdominal and shoulder pain, atrial fibrillation, and subcutaneous hematoma. Two patients had a complication grade 2 (wound infection and decompensated cirrhosis) and one had a grade 4b (sepsis due to pneumonia and urinary tract infection). The median Comprehensive Complication Index was 12.2 (interquartile range 8.7-24.2). Furthermore, univariable logistic regression showed that ≥ 2 tumors treated were associated with a higher risk of complications (odds ratio 6.37, 95% confidence interval [1.20;33.85], p-value = 0.0297). CONCLUSION: Ultrasound-guided laparoscopic microwave ablation of liver malignancies is feasible and safe with little risk for complications, a high technical efficacy, and a low rate of conversions to open procedures.

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.

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.

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.

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.

Colorectal Cancer in Individuals With Familial Adenomatous Polyposis, Based on Analysis of the Danish Polyposis Registry.

BACKGROUND & AIMS: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder that increases risk for colorectal cancer (CRC). We assessed changes in the incidence and prevalence of CRC, and survival times, of patients with FAP participating in the Danish follow-up study. METHODS: We collected data from the Danish Polyposis Registry, a nationwide, complete registry of patients with FAP that includes clinical information, surgical procedures, follow-up findings, and pathology reports. We compared data between the periods of 1990-1999 and 2000-2017. In 2017, the registry contained 226 families with 721 individuals with FAP. Probands were defined as patients diagnosed based on bowel symptoms, without any knowledge of hereditary bowel disease. Call-up patients were defined as those found to have FAP during screening and due to a diagnosis of FAP in first-degree relatives. RESULTS: Although the mean incidence rate of FAP was stable from 1990-1999 (0.19/100,000/year) to 2000-2017 (0.32/100,000/year) (P = .91), the point prevalence increased from 4.86/100,000 in 1999 to 6.11/100,000 by the end of 2017 (P = .005). During 2000-2017, 25 of 72,218 CRC cases were associated with FAP (0.03%)-this was a significant decrease from 1990-1999 (26/30,005 cases; 0.09%) (P = .001). The risk of CRC was significantly higher for probands (n = 191; 61.6%) than call-up cases (n = 5; 1.9%) (P < .001). All CRCs in call-up patients were detected at the diagnosis of FAP (no cases were identified in the follow-up program). The median life expectancy for call-up patients was 72.0 years (95% CI, 63.3-80.7), compared to 55.0 years for probands (95% CI, 51.2-58.8) (P < .001). Therefore, the tracing and follow-up program increased life expectancy by 17.0 years for first-degree family members. CONCLUSION: The Danish Polyposis Registry enables close monitoring of patients with FAP, reducing risk of CRC and prolonging life.

Locoregional treatments before liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry.

Locoregional treatment while on the waiting list for liver transplantation (Ltx) for hepatocellular carcinoma (HCC) has been shown to improve survival. However, the effect of treatment type has not been investigated. We investigate the effect of locoregional treatment type on survival after Ltx for HCC. We investigated patients registered in the European Liver Transplant Registry database using multivariate Cox regression survival analysis. Information on locoregional therapy was registered for 4978 of 23 124 patients and was associated with improved overall survival [hazard ratio (HR) 0.84 (0.73-0.96)] and HCC-specific survival [HR 0.76 (0.59-0.98)]. Radiofrequency ablation (RFA) was the one monotherapy associated with improved overall survival [HR 0.51 (0.40-0.65)]. In addition, the combination of RFA and transarterial chemoembolization also improved survival [HR 0.74 (0.55-0.99)]. Adjusting for factors related to prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial for overall and HCC-specific survival. The effect may represent a selection of patients with favorable tumor biology; however, the treatment may be effective per se by halting tumor progression. Clinicaltrials.gov number: NCT02995096.

Long-term mortality and recurrence in patients treated for colonic diverticulitis with abscess formation: a nationwide register-based cohort study.

PURPOSE: The study aimed to investigate long-term mortality, recurrence, and death related to recurrence for patients admitted with acute diverticulitis with abscess formation (Hinchey stage Ib-II). METHODS: The cohort was identified by linking administrative registers for all Danish citizens in years 2000-2012. Patients were identified from ICD-10 discharge codes and stratified according to treatment (antibiotics, percutaneous abscess drainage, or surgery). RESULTS: From 6,641,672 persons, 3148 patients were identified with acute diverticulitis with abscess formation. Survival was comparable between treatment groups with a 1-year survival of 81-83% and a 5-year survival of 66-67% (p = 0.66). Glucocorticoid usage prior to admission increased risk of mortality with hazard ratio 1.64 (95%CI 1.39-1.93), 1.77 (1.20-2.63), and 1.92 (1.07-3.44) for the antibiotics, drainage, and operative treatment group, respectively. Drainage treatment increased risk of recurrence with sub-distribution hazard (SDH) of 1.52 (1.19-1.95) and operative treatment decreased risk with a SDH of 0.55 (0.32-0.93), both compared with antibiotic treatment (p = 0.0001). Recurrence occurred in 23.6% (18.5-30.1%) of patients in the drainage group, 15.5% (13.9-17.3%) in the antibiotics group, and 9.1% (5.1-16.1%) in the operative group. Recurrence-related mortality was 2.0% (0.9-4.4%) for the drainage group, 1.1% (0.7-1.8%) for the antibiotics group, and 0.6% (0.1-4.3%) for the operative group (p = 0.24). Most recurrences and recurrence-related mortality occurred within the first year after primary admission. CONCLUSIONS: This study with complete national data revealed a high mortality and recurrence rate after diverticular abscesses. Survival was comparable between treatment groups, but patients treated with drainage had significantly higher risk of recurrence.

Emergency admissions for complicated colonic diverticulitis are increasing: a nationwide register-based cohort study.

BACKGROUND: Acute colonic diverticulitis is common in the Western world representing a growing burden on health care. We aimed to report the factual epidemiological and demographic characteristics in patients with acute diverticulitis in a large nationwide population. METHOD: We conducted a population-based cohort study from 2000 to 2012 on the complete Danish population, which included all patients with acute colonic diverticulitis. Data were composed through two national longitudinal registries. The study main outcomes were demographic development regarding hospital admission, age, gender, geographical residency, and seasonal information. RESULTS: A total of 101,963 acute hospital contacts were identified from 2000 to 2012, of these 44,160 were due to acute diverticulitis. From 2000 to 2012, overall admission rates for complicated diverticulitis increased significantly with 42.7%. There was a small increase in hospital admissions due to acute diverticulitis, and uncomplicated diverticulitis accounted for 83-88% of all admissions. No significant development was seen in cases of uncomplicated diverticulitis. The majority of patients were older than 50 years (85%) and 60% were women. The male gender dominated in patients younger than 50 years (58%), whereas women dominated above 50 years (63%). Mean age and dominating age group decreased significantly from 2000 to 2012 for both genders. A significantly larger proportion of male patients had complicated diverticulitis than uncomplicated diverticulitis. Most admissions were seen during autumn. CONCLUSION: We found that acute colonic diverticulitis has been progressing over the last decade with more severe cases of disease. Our findings underline the need for further research to identify the relevant risk factors and causal circumstances.

Use of Ultrasound Contrast Agents in Relation to Percutaneous Interventional Procedures: A Systematic Review and Pictorial Essay.

The aim of this article is to provide an inventory of the use of contrast-enhanced ultrasound (CEUS) in relation to percutaneous interventional procedures. The article is structured into a systematic literature review followed by a clinical part relating to percutaneous CEUS-guided procedures. A literature search identified 3109 records. After abstract screening, 55 articles were analyzed and supplemented with pictorial material to explain the techniques. In conclusion, the best-evidenced indications for CEUS-guided interventions are biopsy and ablation of inconspicuous or B-mode-invisible tumors, intraprocedural ablation control and follow-up, as well as percutaneous transhepatic cholangiography and drainage procedures.

Postoperative complications as a predictor for survival after liver transplantation - proposition of a prognostic score.

BACKGROUND: Liver transplantation is major surgery with a high risk of complications. Existing scoring systems for evaluating complications after surgery are not specific for liver transplantation. Nor are they designed to evaluate the relation to recipient survival or graft loss. We wished to uncover the relation between postoperative complications and one-year risk of death or retransplantation, and to develop a prognostic score for complications based on our findings. METHOD: The study was a retrospective cohort study including 253 adult liver recipients. Thirty-days postoperative complications were registered using the Clavien-Dindo classification. A prognostic score was developed based on types, severity, and quantity of complications. RESULTS: A total of 1113 complications occurred in 233 (92.1%) of the patients. One-year mortality or graft loss was associated with graft, biliary, surgical, systemic, pulmonary, cardiovascular, renal, and infectious complication but not with neurologic or gastrointestinal complications. The developed score was more accurate in predicting the outcome than both the modified Clavien-Dindo score and the Comprehensive Complication Index. CONCLUSION: Types, severity, and quantity of different postoperative complications after liver transplantation are not equally important. The proposed score may focus attention on treating or preventing complications with strong relation to recipient mortality or graft loss.

Vascular invasion and survival after liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry.

BACKGROUND: Studies suggest that vascular invasion may be a superior prognostic marker compared with traditional selection criteria, e.g. Milan criteria. This study aimed to investigate the prognostic value of micro and macrovascular invasion in a large database material. METHODS: Patients liver transplanted for HCC and cirrhosis registered in the European Liver Transplant Registry (ELTR) database were included. The association between the Milan criteria, Up-to-seven criteria and vascular invasion with overall survival and HCC specific survival was investigated with univariate and multivariate Cox regression analyses. RESULTS: Of 23,124 patients transplanted for HCC, 9324 had cirrhosis and data on explant pathology. Patients without microvascular invasion, regardless of number and size of HCC nodules, had a five-year overall survival of 73.2%, which was comparable with patients inside both Milan and Up-to-seven criteria. Patients without macrovascular invasion had an only marginally reduced survival of 70.7% after five years. Patients outside both Milan and Up-to-seven criteria without micro or macrovascular invasion still had a five-year overall survival of 65.8%. CONCLUSION: Vascular invasion as a prognostic indicator remains superior to criteria based on size and number of nodules. With continuously improving imaging studies, microvascular invasion may be used for selecting patients for transplantation in the future.

An 18-Year Nationwide Cohort Study on The Association Between Diverticulitis and Colon Cancer.

OBJECTIVE: To investigate the association between diverticulitis and colon cancer in a large, nationwide cohort study. BACKGROUND: Diverticulitis is a common disease, especially in the Western world. Previous articles have investigated the association between diverticulitis and colon cancer with inconclusive results. METHODS: We conducted a population-based cohort study based on longitudinal Danish national registers with data from the period 1995 to 2012. Data were extracted from comprehensive Danish national registers containing information from both public and private hospitals. Patients with diverticulitis were identified from the registers and matched by sex and age (± 1 year) with a ratio of 1:10 to people who did not have a registration of diverticulitis or diverticulosis. Main outcome was the event of colon cancer. Subgroup analyses were performed to investigate the effect of colonoscopies and treatment on the colon cancer rate after diverticulitis. RESULTS: A total of 445,456 people were included, of whom 40,496 had a diagnosis of diverticulitis. The incidence of colon cancer in the group with diverticulitis (4.3%) and the group without diverticulitis (2.3%) differed significantly (P < 0.001) with an incidence rate ratio of 1.86 (95% confidence interval, CI, 1.77-1.96). When adjusted for possible confounders, the association between diverticulitis and cancer remained significant with an odds ratio (OR) of 2.20 (95% CI 2.08-2.32) (P < 0.001). Those with diverticulitis, who had no colonoscopy, had an increased risk of colon cancer compared with those without both diverticulitis and colonoscopy with an OR of 2.72 (95% CI 2.64-2.94) (P < 0.001). CONCLUSIONS: We found a strong association between development of diverticulitis and colon cancer. This raises several questions regarding the possible causal association and warrants further studies. Patients with diverticulitis should undergo endoscopic surveillance for colon cancer.

Aspirin, Calcitriol, and Calcium Do Not Prevent Adenoma Recurrence in a Randomized Controlled Trial.

BACKGROUND & AIMS: Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of colorectal cancer. We performed a randomized, double-blind, placebo-controlled trial to determine whether a combination of acetylsalicylic acid (aspirin), calcitriol, and calcium carbonate could prevent colorectal adenoma recurrence. METHODS: We included 1107 patients with 1 or more sporadic adenoma(s) removed from the colon or rectum at centers in Europe, Russia, or the United States, from 2004 through 2010. Inclusion criteria were 1 adenoma greater than 1 cm in diameter, more than 1 adenoma of any size, or an adenoma of any size and first-degree relatives with colorectal cancer. Subjects were assigned randomly to groups given 0.5 µg calcitriol, 75 mg acetylsalicylic acid, and 1250 mg calcium carbonate (n = 209), or placebo (n = 218), each day for 3 years. The primary outcome was adenoma recurrence assessed by colonoscopy after 3 years. Secondary outcomes were the proportion of patients with advanced adenomas, the total number of colorectal adenomas, and adenoma size and features. RESULTS: The trial was stopped in October 2010 because of futility. In this analysis, we found no differences between groups in the rate of recurrence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.61-1.48), adverse effects, or secondary outcomes. Subgroup analyses indicated that the treatment effects may be influenced by smoking status (nonsmokers OR, 0.65; 95% CI, 0.26-1.22 vs current smokers OR, 1.70; 95% CI, 0.70-4.09; P value interaction < .05). However, the overall interaction was not significant. CONCLUSIONS: In a prospective study, the combination of calcitriol, aspirin, and calcium carbonate did not prevent recurrence of colorectal adenomas over a 3-year period. The negative results might be owing to the effects of smoking or low doses of the tested agents. Clinicaltrials.gov number: NCT00486512.

The association between location, age and advanced colorectal adenoma characteristics: a propensity-matched analysis.

PURPOSE: Evidence supports an association between certain colorectal adenoma characteristics and predisposition to cancer. The association between anatomical location of colorectal adenoma, age and advanced adenomas needs attention. The objective of this study was to evaluate the possible association between occurrence of sporadic advanced adenomas with location and age. MATERIALS AND METHODS: A cross-sectional study using baseline data from index colonoscopy from a randomized controlled trial evaluating chemopreventive treatment against recurrence of colorectal adenomas was performed. Inclusion criteria for patients were one adenoma of >1 cm in diameter or multiple adenomas of any size, or an adenoma of any size and familial disposition for colorectal cancer. Multivariate regression and propensity score-matched analyses were used to correlate location of adenomas and age with advanced adenoma features. RESULTS: In this study, 2149 adenomas were removed in 1215 patients. Advanced colorectal adenomas primarily occurred in the anal part of the colon. Older age was associated with more adenomas and more oral occurrence of adenomas, as well as a higher risk of advanced adenomas. Surprisingly, specifically for the oral adenomas the risk of advanced adenoma seems to be lower for older patients compared with younger. CONCLUSIONS: This study presents new results with regard to association between age, location of adenomas and risk of advanced adenomas. The results indicate that sigmoidoscopy for screening purposes may be obsolete, and add to the existing literature on which future guidelines for screening may be based.

Risk factors for recurrence after acute colonic diverticulitis: a systematic review.

PURPOSE: Several factors may influence the risk of recurrence after an episode of acute colonic diverticulitis. Until now, a comprehensive systematic overview and evaluation of relevant risk factors have not been presented. This review aimed at assembling and evaluating current evidence on risk factors for recurrence after conservatively treated acute colonic diverticulitis. METHODS: PubMed, Embase, and Cochrane databases were searched for studies evaluating risk factors for recurrence after acute diverticulitis treated non-surgically defined as antibiotic treatment, percutaneous abscess drainage, or by observation. Randomized clinical trials and observational studies were included. Analyzed outcome variables were extracted and grouped. No meta-analysis was performed due to low inter-study comparability. Variables were rated according to their likelihood of causing recurrence (no/low, medium, high). RESULTS: Of 1153 screened records, 35 studies were included, enrolling 396,676 patients with acute diverticulitis. A total of 50,555 patients experienced recurrences. Primary diverticulitis with abscess formation and young age increased the risk of recurrence. Readmission risk was higher within the first year after remission. In addition, the risk of subsequent diverticulitis more than doubled after two earlier episodes of diverticulitis and the risk increased further for every episode. CONCLUSIONS: The best treatment strategy for recurrent diverticulitis is undetermined. However, the risk of a new recurrence seemed to increase after each recurrence making elective resection a viable option at some point after multiple recurrences depending on patient risk factors and preferences.