Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for ...observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.
Acute pancreatitis may be a risk factor for pancreatic cancer; however, findings from studies on this association are conflicting. We investigated the association between acute pancreatitis and ...increased risk of pancreatic cancer.
We conducted a nationwide, population-based, matched cohort study of all patients admitted to a hospital in Denmark with a diagnosis of acute pancreatitis from January 1, 1980, through October 31, 2012. As many as 5 individuals from the general population without acute pancreatitis were matched for age and sex to each patient with acute pancreatitis. Pancreatic cancer risk was expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), calculated using the Cox proportional hazards model. Cox models were stratified by age, sex, and year of pancreatitis diagnosis and adjusted for alcohol- and smoking-related conditions, and Charlson Comorbidity Index score.
We included 41,669 patients diagnosed with incident acute pancreatitis and 208,340 comparison individuals. Patients with acute pancreatitis had an increased risk of pancreatic cancer compared with the age- and sex-matched general population throughout the follow-up period. The risk decreased over time but remained high after more than 5 years of follow-up (adjusted HR 2.02; 95% CI 1.57–2.61). Two- and 5-year absolute risks of pancreatic cancer among patients with acute pancreatitis were 0.70% (95% CI 0.62%–0.78%) and 0.87% (95% CI 0.78%–0.97), respectively.
In a nationwide, population-based, matched cohort study, we observed an association between a diagnosis of acute pancreatitis and long-term risk of pancreatic cancer.
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Purpose
To compare the diagnostic performance of contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI) and combined fluorodeoxyglucose/positron emission tomography/computed ...tomography (FDG-PET/CT) for detection of colorectal liver metastases (CRLM) in patients eligible for local treatment.
Materials and methods
This health-research ethics-committee-approved prospective consecutive diagnostic accuracy study, with written informed consent, included 80 cases (76 patients, four participating twice) between 29 June 2015 and 7 February 2017. Prior chemotherapy or local treatment did not exclude participation. Combined FDG-PET/CT including CE-CT and MRI was performed within 0–3 days shortly before local treatment. CE-CT and MRI images were read independently by two readers for each modality. The combined FDG-PET/CT images were read independently by two pairs of readers. A composite reference standard was used. Sensitivities, specificities and area under the receiver operating characteristic curves (AUC
ROC
) were calculated and compared.
Results
In total, 260 CRLMs were confirmed. The MRI readers had significantly higher per-lesion sensitivity (85.9% and 83.8%) than both CE-CT readers (69.1% and 62.3%) and both PET/CT reader pairs (72.0% and 72.1%) (
p
<0.001). There were no significant differences in per-lesion specificity. MRI readers had significantly higher AUC
ROC
(0.92 and 0.88) than both CE-CT readers (0.80 and 0.82) (
p
≤0.001). AUC
ROC
for MR reader 1 was higher than that of both PET/CT reader pairs (0.83 and 0.84) (
p
≤0.0001).
Conclusion
MRI performed significantly better than both CE-CT and combined FDG-PET/CT for detection of CRLM in consecutive patients eligible for local treatment irrespective of prior chemotherapy or local treatment.
Key Points
• Patients eligible for local treatment of colorectal liver-metastases require optimal imaging.
• In 80 consecutive patients, MRI had superior per lesion diagnostic performance.
• Findings were independent of prior treatment and type of planned local treatment.
• Equally, MRI had superior diagnostic performance on per segment basis.
It is unknown whether urban versus rural residency affects pancreatic cancer survival in a universal tax-financed healthcare system. We conducted a nationwide, population-based cohort study of all ...patients diagnosed with pancreatic cancer in Denmark from 2004-2015. We used nationwide registries to collect information on characteristics, comorbidity, cancer-directed treatment, and vital status. We followed the patients from pancreatic cancer diagnosis until death, emigration, or 1 October 2017, whichever occurred first. We truncated at five years of follow up. We stratified patients into calendar periods according to year of diagnosis (2004-2007, 2008-2011, and 2012-2015). We used Cox proportional hazards model to compute hazard ratios (HRs) with associated 95% confidence intervals (CIs) of death, comparing patients in urban and rural areas. HRs were adjusted for age, sex, comorbidity, tumor stage, and localization. In a sub-analysis, we also adjusted for cancer-directed treatment. We included 10,594 patients diagnosed with pancreatic cancer. Median age was 71 years (inter-quartile range: 63-78 years), and half were men. The majority (61.7%) lived in an urban area at the time of diagnosis. When adjusting for potential confounders, we observed a better survival rate among pancreatic cancer patients residing in urban areas compared with rural areas (adjusted HR: 0.92; 95% CI: 0.87-0.98). When taking treatment into account, the association was unclear (adjusted HR: 0.96; 95% CI: 0.88-1.04). Pancreatic cancer patients residing in urban areas had a slightly better survival rate compared with patients in rural areas.
Objective
The objective of this study is to investigate the impact of ketorolac and other nonsteroidal anti-inflammatory drugs on anastomotic leakage after surgery for gastro-esophageal-junction ...cancer.
Summary Background Data
Within the last two decades, the incidence of gastro-esophageal-junction cancer has increased in the western world and surgery is the curative treatment modality of choice. Anastomotic leakage is a feared complication of gastro-esophageal surgery, as it increases recurrence, morbidity, and mortality. Nonsteroidal anti-inflammatory drugs are widely used for postoperative pain relief. Nonsteroidal anti-inflammatory drugs have, however, in colorectal surgery, been shown to increase the risk of anastomotic leakage.
Method
In a historical cohort study, we investigated the impact of nonsteroidal anti-inflammatory drugs on anastomotic leakage in 557 patients undergoing surgery for gastro-esophageal-junction cancer. Data were collected from a prospective maintained database, the Danish National Patient Registry, and patient medical records. Data were analyzed using univariate and multivariate statistical models and were stratified for theoretical confounders.
Results
In univariate analysis, we did not observe any difference in age, gender, tobacco exposure, or comorbidity status between patients experiencing anastomotic leakage and those without. In multivariate analysis, gender, histology, and type of anastomosis proved to affect odds ratios for anastomotic leakage. After adjustment for possible confounders, we found an odds ratio of 6.05 (95% confidence interval 2.71; 13.5) for ketorolac use and of 5.24 (95% confidence interval 1.85; 14.8) for use of other nonsteroidal anti-inflammatory drugs for anastomotic leakage during the first seven postoperative days.
Conclusion
In the present study, we found a strong association between the postoperative use of ketorolac and other nonsteroidal anti-inflammatory drugs and the risk for anastomotic leakage after surgery for gastro-esophageal-junction cancers.
The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats ...were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.
About 10–20% of patients with metastatic colorectal cancer (mCRC) are candidates for metastasis directed therapies such as surgical resection, ablation and stereotactic radiotherapy. We examined the ...temporal changes in use of metastasis directed therapies and established prognostic factors for survival in a nationwide cohort study. The Danish nationwide medical registries were used to retrieve data on treatment for liver and/or lung metastasis in patients with metastatic colorectal cancer in the period 2000–2013. Overall survival through 2014 was calculated from the time of treatment of metastases by Kaplan–Meier method and mortality between groups was assessed using Cox regression. We report 2,912 patients undergoing a total of 3,602 procedures with an increased use of all modalities during 14 calendar years. Median survival was 3.7 years (interquartile range (IQR) 2.0–9.7 years). In the multivariate analysis, the nodal stage of the primary tumor had the most pronounced association with survival with a hazard ratio for mortality of 1.56 (95% CI: 1.33–1.83) for N2 stage with reference to N0. Furthermore, female gender, age, comorbidity, surgical treatment, administration of chemotherapy, and left‐sided primary tumors were associated with improved prognosis in the multivariate analysis.
What's new?
The treatment of metastatic colorectal cancer (mCRC) centers primarily on surgical resection, ablative therapy, and stereotactic radiotherapy. Little is known, however, about recent trends in the use of these treatments for mCRC. Here, analyses of data from nationwide medical registries in Denmark reveal temporal changes in the use of metastasis‐directed therapies over the period 2000–2013. Specifically, the use of all three modalities—resection, ablation, and stereotactic radiotherapy—increased for liver and lung metastases from mCRC. Median survival was 3.7 years for patients undergoing metastasis‐directed therapy, indicating an improvement in long‐term survival for this patient subset.
Normal liver tissue is highly vulnerable towards irradiation, which remains a challenge in radiotherapy of hepatic tumours. Here, we examined the effects of radiation-induced liver injury on two ...specific liver functions and hepatocellular regeneration in a minipig model. Five Göttingen minipigs were exposed to whole-liver stereotactic body radiation therapy (SBRT) in one fraction (14 Gy) and examined 4-5 weeks after; five pigs were used as controls. All pigs underwent in vivo positron emission tomography (PET) studies of the liver using the conjugated bile acid tracer N-methyl-
Ccholylsarcosine (
CCSar) and the galactose-analogue tracer
Ffluoro-2-deoxy-D-galactose (
FFDGal). Liver tissue samples were evaluated histopathologically and by immunohistochemical assessment of hepatocellular mitosis, proliferation and apoptosis. Compared with controls, both the rate constant for secretion of
CCSar from hepatocytes into intrahepatic bile ducts as well as back into blood were doubled in irradiated pigs, which resulted in reduced residence time of
CCSar inside the hepatocytes. Also, the hepatic systemic clearance of
FFDGal in irradiated pigs was slightly increased, and hepatocellular regeneration was increased by a threefold. In conclusion, parenchymal injury and increased regeneration after whole-liver irradiation was associated with enhanced hepatobiliary secretion of bile acids. Whole-liver SBRT in minipigs ultimately represents a potential large animal model of radiation-induced liver injury and for testing of normal tissue protection methods.
Background: Adjuvant chemotherapy following curative resection is the standard treatment for pancreatic adenocarcinoma (PC). Randomized clinical trials using gemcitabine have shown a median overall ...survival (mOS) of 2 years and a 5-year survival rate of 15-20%. However, the effect of gemcitabine outside these trials is less clear. We examined the effect of postoperative gemcitabine on survival in an unselected cohort of patients receiving curative resection for PC in Denmark during a five-year period.
Material and methods: From 1 May 2011 to 30 April 2016, 731 patients treated with curative resection were identified in the Danish Pancreatic Cancer Database (DPCD). Thirty patients died within 10 weeks postoperatively; 78 received other regimens or preoperative chemotherapy and were excluded. Of the remaining 623 patients, the chemotherapy (CT) group (n = 409, 66%) received gemcitabine within 10 weeks after resection, whereas the non-chemotherapy (NCT) group (n = 214, 34%) did not receive CT within 10 weeks.
Results: CT patients were slightly younger than NCT patients but did not otherwise differ in baseline characteristics. The CT group showed a mOS of 24 months (95% CI; 21-27) and a 5-year survival rate of 22% (95% CI; 17-27); the NCT group had a mOS of 22 months (95% CI; 16-26, p = .27) and a 5-year survival rate of 26% (95% CI; 19-34, p = .66). Most patients (415/623) had lymph node metastases. Of these patients, those in the CT group (n = 280) had significantly longer mOS 20 months (95% CI; 18-24) than those in the NCT group (n = 135) 14 months (95% CI; 11-17).
Conclusions: In this national Danish cohort of PC patients undergoing resection between 2011 and 2016, the survival after postoperative gemcitabine was similar to that reported in previous clinical trials. However, the survival advantage of postoperative gemcitabine was limited to patients with lymph node metastases.
Background
Parasympathetic neuropathy is a key feature in many common disorders, including diabetes, neurological disorders, and cancers, but few objective methods exist for assessing damage to the ...parasympathetic nervous system, particularly in the gastrointestinal system. This study aimed to validate the use of 11C‐donepezil positron emission tomography (PET) to assess parasympathetic integrity in a group of vagotomized patients.
Methods
Sixteen healthy controls and 12 patients, vagotomized due to esophagectomy, underwent 11C‐donepezil PET, measurement of colonic transit time, quantification of plasma pancreatic polypeptide (PP), and assessment of subjective long‐term symptoms.
Key Results
Vagotomized patients had significantly decreased PET signal in the small intestine and colon compared with healthy controls (5.7 4.4‐7.9 vs 7.4 4.5‐11.3, P = .01 and 1.4 1.1‐2.1 vs 1.6 1.4‐2.4, P < .01, respectively). Vagotomized patients also displayed a significantly increased colonic transit time (2.9 ± 0.9 h vs 1.9 ± 0.8 h), P < .01 and increased volumes of the small intestine and colon (715 ccm 544‐1177 vs 443 ccm 307‐613, P < .01 and 971 ccm 713‐1389 vs 711 ccm 486‐1394, P = .01, respectively). Patients and controls did not differ in PP ratio levels after sham feeding, but PP ratio at 10 minutes. after sham feeding and PET signal intensity in the small intestine was positively correlated (P = .03).
Conclusions and Inferences
We found significantly decreased 11C‐donepezil signal in the intestine of vagotomized patients, supporting that 11C‐donepezil PET is a valid measure of intestinal parasympathetic denervation.
We have conducted the first PET/CT study of cholinergic innervation of the gut in patients with esophagus cancer, who received radical surgical esophagectomy including vagotomy with comparison to healthy matched controls. We detected significantly decreased 11C‐donepezil PET signal in the small intestine and colon of vagotomized patients treated for esophagus cancer, suggesting that 11C‐donepezil PET can be used to assess damage to the parasympathetic nervous system in the GI‐tract.
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