Assessing Patient Radiation Exposure in Endoscopic Retrograde Cholangiopancreatography: A Multicenter Retrospective Analysis of Procedural Complexity and Clinical Factors.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) procedures can result in significant patient radiation exposure. This retrospective multicenter study aimed to assess the influence of procedural complexity and other clinical factors on radiation exposure in ERCP. METHODS: Data on kerma-area product (KAP), air-kerma at the reference point (Ka,r), fluoroscopy time, and the number of exposures, and relevant patient, procedure, and operator factors were collected from 2641 ERCP procedures performed at four university hospitals. The influence of procedural complexity, assessed using the American Society for Gastrointestinal Endoscopy (ASGE) and HOUSE complexity grading scales, on radiation exposure quantities was analyzed within each center. The procedures were categorized into two groups based on ERCP indications: primary sclerosing cholangitis (PSC) and other ERCPs. RESULTS: Both the ASGE and HOUSE complexity grading scales had a significant impact on radiation exposure quantities. Remarkably, there was up to a 50-fold difference in dose quantities observed across the participating centers. For non-PSC ERCP procedures, the median KAP ranged from 0.9 to 64.4 Gy·cm2 among the centers. The individual endoscopist also had a substantial influence on radiation dose. CONCLUSIONS: Procedural complexity grading in ERCP significantly affects radiation exposure. Higher procedural complexity is typically associated with increased patient radiation dose. The ASGE complexity grading scale demonstrated greater sensitivity to changes in radiation exposure compared to the HOUSE grading scale. Additionally, significant variations in dose indices, fluoroscopy times, and number of exposures were observed across the participating centers.

Endoscopic papillectomy for ampullary lesions of minor papilla.

BACKGROUND AND AIMS: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. METHODS: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. RESULTS: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). CONCLUSIONS: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.

Clinical characteristics and long-term outcomes following pancreatic injury - An international multicenter cohort study.

Background: Trauma to the pancreas is rare but associated with significant morbidity. Currently available management guidelines are based on low-quality evidence and data on long-term outcomes is lacking. This study aimed to evaluate clinical characteristics and patient-reported long-term outcomes for pancreatic injury. Methods: A retrospective cohort study evaluating treatment for pancreatic injury in 11 centers across 5 European nations over >10 years was performed. Data relating to pancreatic injury and treatment were collected from hospital records. Patients reported quality of life (QoL), changes to employment and new or ongoing therapy due to index injury. Results: In all, 165 patients were included. The majority were male (70.9%), median age was 27 years (range: 6-93) and mechanism of injury predominantly blunt (87.9%). A quarter of cases were treated conservatively; higher injury severity score (ISS) and American Association for the Surgery of Trauma (AAST) pancreatic injury scores increased the likelihood for surgical, endoscopic and/or radiologic intervention. Isolated, blunt pancreatic injury was associated with younger age and pancreatic duct involvement; this cohort appeared to benefit from non-operative management. In the long term (median follow-up 93; range 8-214 months), exocrine and endocrine pancreatic insufficiency were reported by 9.3% of respondents. Long-term analgesic use also affected 9.3% of respondents, with many reported quality of life problems (QoL) potentially attributable to side-effects of opiate therapy. Overall, impaired QoL correlated with higher ISS scores, surgical therapy and opioid analgesia on discharge. Conclusions: Pancreatic trauma is rare but can lead to substantial short- and long-term morbidity. Near complete recovery of QoL indicators and pancreatic function can occur despite significant injury, especially in isolated, blunt pancreatic injury managed conservatively and when early weaning off opiate analgesia is achieved.

Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

Long-Term Follow-up and Risk of Recurrence of Internal Herniation after Roux-en-Y Gastric Bypass.

PURPOSE: Internal herniation (IH) is the most common complication after Roux-en-Y gastric bypass surgery (RYGB). Although primary closure has reduced the incidence, recurrences are a continued problem. This study aimed to investigate long-term follow-up and recurrence risk of IH surgery. METHODS: A retrospective cohort study of laparoscopic RYGB operated patients operated for a first IH between April 2012 and April 2015 at Skåne University Hospital in Malmö, Sweden. Status of primary closure of mesenteric gaps, time since RYGB, and findings at IH surgery were retrieved from medical records. Follow-up until December 31st, 2019, included recurrences of IH, number of computed tomography (CT) scans, emergency visits, readmissions, and other acute surgeries. RESULTS: IH (n = 44) occurred almost equally in Petersen's space (n = 24) and beneath the jejunojejunostomy (n = 20). Long-term follow-up (median 75 months) of 43 patients registered an IH recurrence rate of 14% (n = 6). All recurrences occurred in the other mesenteric gap. One patient suffered a third IH, and one patient had four IH events. During follow-up, 56% (n = 24) had ER visits for abdominal pain, 47% (n = 20) had ≥ 1 abdominal CT scan, and 40% (n = 17) were readmitted. A third of readmitted (6/17) patients suffered a recurrence of internal herniation. Two other patients were readmitted ≥ 10 times for chronic abdominal pain. CONCLUSION: Surgery for IH had a low risk of recurrence at the treated mesenteric gap, but a 14% recurrence risk at the other mesenteric gap, emphasizing the importance of carefully investigating weaknesses or gaps at the other mesenteric defect during surgery for IH.

Postoperative three-dimensional endoanal ultrasound findings and relation to anal fistula plug failure.

OBJECTIVES: To explore the utilization of three-dimensional (3D) endoanal ultrasound (EAUS) for the follow-up of the anal fistula plug (AFP), describe morphological findings in postoperative 3D EAUS, and evaluate if postoperative 3D EAUS combined with clinical symptoms can predict AFP failure. MATERIALS AND METHODS: A retrospective analysis of 3D EAUS examinations performed during a single-centre study of prospectively included consecutive patients treated with the AFP between May 2006 and October 2009. Postoperative assessment by clinical examination and 3D EAUS was performed at 2 weeks, 3 months and 6-12 months ("late control"). Long-term follow-up was carried out in 2017. The 3D EAUS examinations were blinded and analysed by two observers using a protocol with defined relevant findings for different follow-up time points. RESULTS: A total of 95 patients with a total of 151 AFP procedures were included. Long-term follow-up was completed in 90 (95%) patients. Inflammation at 3 months, gas in fistula and visible fistula at 3 months and at late control, were statistically significant 3D EAUS findings for AFP failure. The combination of gas in fistula and clinical finding of fluid discharge through the external fistula opening 3 months postoperatively was statistically significant (p < 0.001) for AFP failure with 91% sensitivity and 79% specificity. The positive predictive value was 91%, while the negative predictive value was 79%. CONCLUSIONS: 3D EAUS may be utilized for the follow-up of AFP treatment. Postoperative 3D EAUS at 3 months or later, especially if combined with clinical symptoms, can be used to predict long-term AFP failure.ClinicalTrials.gov identifier NCT03961984.

Laparoscopic transcystic common bile duct exploration versus transgastric endoscopic retrograde cholangiography during cholecystectomy after Roux-en-Y gastric bypass.

BACKGROUND: Treatment of common bile duct (CBD) stones after Roux-en-Y gastric bypass (RYGB) poses a particular challenge given the altered anatomy and inability to perform a standard endoscopic retrograde cholangiogram (ERC). The optimal treatment strategy for intraoperatively encountered CBD stones in post-RYGB patients has not been established. OBJECTIVES: To compare outcomes following laparoscopic transcystic common bile duct exploration (LTCBDE) and laparoscopy-assisted transgastric ERC for CBDs during cholecystectomy in RYGB-operated patients. SETTING: Swedish nationwide multi-registry study. METHODS: The Swedish Registry for Gallstone Surgery and ERCs, GallRiks (n = 215,670), and the Scandinavian Obesity Surgery Registry (SOReg) (n = 60,479) were cross-matched for cholecystectomies with intraoperatively encountered CBD stones in patients with previous RYGB surgery between 2011 and 2020. RESULTS: Registry cross-matching found 550 patients. Both LTCBDE (n = 132) and transgastric ERC (n = 145) were comparable in terms of low rates of intraoperative adverse events (1% versus 2%) and postoperative adverse events within 30 days (16% versus 18%). LTCBDE required significantly shorter operating time (P = .005) by on average 31 minutes, 95% confidence interval (CI) [10.3-52.6], and was more often used for smaller stones <4 mm in size (30% versus 17%, P = .010). However, transgastric ERC was more often used in acute surgery (78% versus 63%, P = .006) and for larger stones >8 mm in size (25% versus 8%, P < .001). CONCLUSIONS: LTCBDE and transgastric ERC have similarly low complication rates for clearance of intraoperatively encountered CBD stones in RYGB-operated patients, but LTCBDE is faster while transgastric ERC is more often used in conjunction with larger bile duct stones.

Endoscopic papillectomy for ampullary lesions in patients with familial adenomatous polyposis compared with sporadic lesions: a propensity score-matched cohort.

BACKGROUND: Familial adenomatous polyposis (FAP) is a rare inherited syndrome that predisposes the patient to cancer. Treatment of FAP-related ampullary lesions is challenging and the role of endoscopic papillectomy has not been elucidated. We retrospectively analyzed the outcomes of endoscopic papillectomy in matched cohorts of FAP-related and sporadic ampullary lesions (SALs). METHODS: This retrospective multicenter study included 1422 endoscopic papillectomy procedures. Propensity score matching including age, sex, comorbidity, histologic subtype, and size was performed. Main outcomes were complete resection (R0), technical success, complications, and recurrence. RESULTS: Propensity score matching identified 202 patients (101 FAP, 101 SAL) with comparable baseline characteristics. FAP patients were mainly asymptomatic (79.2 % [95 %CI 71.2-87.3] vs. 46.5 % [95 %CI 36.6-56.4]); P < 0.001). The initial R0 rate was significantly lower in FAP patients (63.4 % [95 %CI 53.8-72.9] vs. 83.2 % [95 %CI 75.8-90.6]; P = 0.001). After repeated interventions (mean 1.30 per patient), R0 was comparable (FAP 93.1 % [95 %CI 88.0-98.1] vs. SAL 97.0 % [95 %CI 93.7-100]; P = 0.19). Adverse events occurred in 28.7 %. Pancreatitis and bleeding were the most common adverse events in both groups. Severe adverse events were rare (3.5 %). Overall, 21 FAP patients (20.8 % [95 %CI 12.7-28.8]) and 16 SAL patients (15.8 % [95 %CI 8.6-23.1]; P = 0.36) had recurrence. Recurrences occurred later in FAP patients (25 [95 %CI 18.3-31.7] vs. 2 [95 %CI CI 0.06-3.9] months). CONCLUSIONS: Endoscopic papillectomy was safe and effective in FAP-related ampullary lesions. Criteria for endoscopic resection of ampullary lesions can be extended to FAP patients. FAP patients have a lifetime risk of relapse even after complete resection, and require long-time surveillance.

Outcomes of rescue procedures in the management of locally recurrent ampullary tumors: A Pancreas 2000/EPC study.

BACKGROUND: Ampullary lesions are rare and can be locally treated either with endoscopic papillectomy or transduodenal surgical ampullectomy. Management of local recurrence after a first-line treatment has been poorly studied. METHODS: Patients with a local recurrence of an ampullary lesion initially treated with endoscopic papillectomy or transduodenal surgical ampullectomy were retrospectively included from a multi-institutional database (58 centers) between 2005 and 2018. RESULTS: A total of 103 patients were included, 21 (20.4%) treated with redo endoscopic papillectomy, 14 (13.6%) with transduodenal surgical ampullectomy, and 68 (66%) with pancreaticoduodenectomy. Redo endoscopic papillectomy had low morbidity with 4.8% (n = 1) severe to fatal complications and a R0 rate of 81% (n = 17). Transduodenal surgical ampullectomy and pancreaticoduodenectomy after a first procedure had a higher morbidity with Clavien III and more complications, respectively, 28.6% (n = 4) and 25% (n = 17); R0 resection rates were 85.7% (n = 12) and 92.6% (n = 63), both without statistically significant difference compared to endoscopic papillectomy (P = .1 and 0.2). Pancreaticoduodenectomy had 4.4% (n = 2) mortality. No deaths were registered after transduodenal surgical ampullectomy or endoscopic papillectomy. Recurrences treated with pancreaticoduodenectomy were more likely to be adenocarcinomas (79.4%, n = 54 vs 21.4%, n = 3 for transduodenal surgical ampullectomy and 4.8%, n = 1 for endoscopic papillectomy, P < .0001). Three-year overall survival and disease-free survival were comparable. CONCLUSION: Endoscopy is appropriate for noninvasive recurrences, with resection rate and survival outcomes comparable to surgery. Surgery applies more to invasive recurrences, with transduodenal surgical ampullectomy rather for carcinoma in situ and early cancers and pancreaticoduodenectomy for more advanced tumors.

Intussusception After Roux-en-Y Gastric Bypass: Correlation Between Radiological and Operative Findings.

INTRODUCTION: Intussusceptions diagnosed on computed tomography (CT) scans in Roux-en-Y gastric bypass (RYGB) patients could cause serious small bowel obstruction (SBO) or be an incidental finding. The objective of this study was to correlate radiological findings with clinical outcomes to differentiate intussusceptions requiring emergent surgery for SBO. METHODS: A search for acute abdominal CT scans reporting intussusceptions in RYGB patients between 2012 and 2019 at Skåne University Hospital, Malmö, Sweden, retrieved 35 scans. These were independently reevaluated by two radiologists for the length and location of the intussusception, whether oral contrast passed through, proximal bowel dilatation, and signs of internal herniation. Clinical outcome in terms of emergency surgery and the diagnosis was determined through chart review. RESULTS: Out of 35 acute patients, 9 patients required emergency surgery within 24 h. Intussusception caused SBO in five patients, and one patient had an internal herniation, while three patients had unremarkable findings. Eight patients were evaluated for intermittent pain with five unremarkable laparoscopies, while 18 patients had intussusceptions as incidental findings. Intussusception length on CT as measured by radiologists O.E. and D.L. predicted acute bowel obstruction (p = .014 and p < .001). A 100 mm threshold predicted bowel obstruction with a sensitivity of 80% and 100% and a specificity of 93% and 86% by radiologists O.E. and D.L., respectively. Proximal bowel dilatation predicted SBOs of any cause as well as SBO caused by an intussusception (all p < .05). CONCLUSION: Intussusception length > 100 mm on CT in RYGB patients is an easy and valuable sign indicating SBO that may require emergent surgery.

The role of citrulline, intestinal fatty acid-binding protein, and D-dimer as potential biomarkers in the diagnosis of internal herniation after Roux-en-Y gastric bypass.

BACKGROUND: Diagnosing internal herniation (IH) in Roux-en-Y gastric bypass (RYGB) patients with acute abdominal pain poses a diagnostic challenge. Diagnostic laparoscopy is often required for a definitive diagnosis. We hypothesized that intestinal ischemia biomarkers would aid in the diagnosing of IH. OBJECTIVES: To explore intestinal ischemia biomarkers in diagnosing IH. SETTING: University Hospital, Sweden. METHODS: Prospective inclusion of 46 RYGB patients admitted for acute abdominal pain between June 2015 and December 2017. Blood samples for analysis of citrulline, intestinal fatty acid-binding protein (I-FABP), and D-dimer were drawn <72 hours from admission and compared between patients with IH (n = 8), small bowel obstruction (SBO) (n = 5), other specified diagnoses (n = 12), or unspecified abdominal pain (n = 21). Levels of white blood cell count (WBC), C-reactive protein (CRP), and lactate at admission were compared. A prospective pain questionnaire for time of pain onset and level of pain at onset and at admission was analyzed. RESULTS: None of the investigated biomarkers differed significantly between diagnosis categories. Most patients with IH had normal CRP, WBC, and D-dimer levels while their lactate levels were significantly lower (P = .029) compared with the rest of the cohort. Neither pain level nor pain duration differed between the groups. CONCLUSION: This study shows that citrulline, I-FABP, and D-dimer cannot be used to diagnose IH and indicates that CRP, D-dimer, and lactate are rarely elevated by an IH. Furthermore, pain intensity and duration cannot differentiate patients with IH. A diagnostic laparoscopy remains the gold standard to diagnose and rule out an IH.

Differences in Health-Related Quality of Life After Gastric Bypass Surgery: a Cross-Sectional Study.

BACKGROUND: Gastric bypass (GBP) is a surgical method with good evidence of sustainable weight loss, reduced obesity-related comorbidities, and improved health-related quality of life (HRQoL). However, long-term data post-GBP is scarce on HRQoL related to other factors than weight loss, such as impact of socio-economic, age, and gender. AIM: To investigate long-term HRQoL in GBP patients. METHODS: The study was conducted as a cross-sectional study covering 3 to 9 years post-GBP measuring HRQoL using RAND-36. Association to weight loss, time since surgery, gender, educational level, occupation, and age was analyzed. The participants were included on the basis that they had received a GBP that was performed by Region Skåne, the southernmost administrative healthcare region in Sweden. Recruitment to the study was by mail invitation for an online survey. RESULTS: Of the total population of 5310 persons receiving the questionnaire, 1339 of the 1372 responders fulfilled the inclusion criteria. Those with low educational level, unemployed, persons on sick leave or disability support, and those with less weight loss reported the lowest HRQoL. The longer time since surgery, the lower the HRQoL. CONCLUSION: Less weight loss, longer time since GBP, lower educational level, and lower degree of employment all affect HRQoL negatively after GBP surgery.

The Initial Course of IL1ß, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α with Regard to Severity Grade in Acute Pancreatitis.

Clinical reports on early immune dysregulation in acute pancreatitis (AP) are scarce. Herein we investigate the initial temporal development of selected biomarkers. Blood samples were taken at 0-24 and 25-48 h after onsets of AP were acquired. Mean values and temporal intermediate difference (delta-values) of IL-1ß, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were calculated. Differences between severity groups, predictive capacity of the biomarkers and association with severe disease were analyzed. Paired comparison of samples (n = 115) taken at 0-24 and 25-48 h after onsets of AP showed a change over time for IL-1ß, IL-6, IL-8 and IL-10 (p < 0.05) and a significant difference between severity groups after 24 h. In ROC-analysis an IL-6 cut-off level of 196.6 pg/mL could differentiate severe AP (sensitivity 81.9, specificity 91.3). The delta-values of IL-1ß and IL-6 were significantly associated with severe outcomes (odds ratios 1.085 and 1.002, respectively). Data of this work demonstrate a distinct change in IL-1ß, IL-8, IL-10 and IL-6 over the first 48 h after onset of AP. The temporal development of biomarkers can assist in the early stratification of the disease. Herein IL-1ß and IL-6 were associated with severe disease, however the prognostic capacity of investigated biomarkers is low.

[Short report of Swedish guidelines for Acute Pancreatitis]. / Nya nationella riktlinjer för handläggning av akut pankreatit.

This is a short report of the recently published Swedish guidelines for acute pancreatitis, which are based on international guidelines as well as original publications. The report covers diagnosis, classification, treatment and follow up for patients with acute pancreatitis. Early rehydration and goal-based fluid therapy is recommended as well as oral intake of food on demand. Risk factors for development of severe disease and organ failure should be considered already in the emergency unit. Abdominal computer tomography is generally not recommended the first 5-7 days from onset of symptoms. Antibiotic therapy is only recommended when there is suspicion of or a confirmed infection. If intervention is needed for patients with moderate or severe disease a minimal-invasive step-up approach is recommended. Endoscopic Retrograde Cholangiography is generally not recommended as a treatment in the acute phase of the disease. Identification and treatment of the etiology causing acute pancreatitis is essential to prevent new episodes of the disease.

Abdominal pain after gastric bypass in the acute general surgical care setting.

BACKGROUND: Managing acute abdominal pain in the large and growing population of Roux-en-Y gastric bypass (RYGB)-operated patients poses a challenge to general surgeons, because of diagnostic limitations and the risk of internal herniation. OBJECTIVE: To investigate the diagnoses, management, and outcome of RYGB patients admitted for acute abdominal pain. SETTING: University Hospital, Sweden. METHODS: Prospective inclusion of 280 consecutive RYGB patients admitted for acute abdominal pain between April 2012 and June 2015. Readmissions, surgical procedures, and overall mortality were recorded until October 2018. Medical records were retrospectively reviewed for anthropometric measures, medical history, time from RYGB surgery, and previous closure of mesenteric gaps. Admissions were separated into early (≤30 d) or late (>30 d) after RYGB. Procedures performed were categorized as follows: RYGB complication, other surgery, or unremarkable laparoscopy. Patients discharged with diagnosis of unspecified abdominal pain were separately analyzed. Diagnostic investigations, bariatric competency, on call surgery, surgical complications, and length of stay were registered. RESULTS: In late admissions, the cause of the abdominal complaints remained unexplained in 127 of 262 (48%) patients despite 95 abdominal computed tomographies and 28 diagnostic laparoscopies. Emergency surgery was performed in 128 of 262 (49%) patients. RYGB complications (n = 66), mainly internal herniation (n = 42), were >2 times more frequent than other surgical procedures (n = 32), such as cholecystectomies (n = 23). Internal herniation could occur at any time interval from RYGB surgery and regardless of previously closed mesenteric gaps. CONCLUSION: Better tools for evaluation of acute abdominal pain in RYGB patients are needed to reduce the number of unremarkable laparoscopies and admissions of patients with unspecified abdominal pain.

Study Protocol of the ESAP Study: Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodenectomy for Ampullary Neoplasm-A Pancreas2000/EPC Study.

Background: Lesions of the Ampulla of Vater are a rare condition and represent <10% of peri-ampullary neoplasms. Nevertheless, ampullary adenomas have the potential for malignant transformation to ampullary carcinomas by an adenoma-to-carcinoma sequence. Thus, adequate patient selection and complete resection (R0) of non-invasive ampullary lesions either by endoscopic papillectomy (EP), surgical ampullectomy (SA), or pancreaticoduodenectomy (PD) is essential. Although PD was traditionally performed, recent studies reported considerable efficacy and fewer complications following EP and SA. Since consistent comparative data are lacking, the Endoscopic Papillectomy vs. Surgical Ampullectomy vs. Pancreaticoduodectomy (ESAP) study will provide evidence for a therapeutic standard and post procedure morbidity in ampullary lesions. Methods: International multicenter retrospective study. Adult patients (>18 years of age) who underwent SA or PD for ampullary neoplasm between 2004 and 2018 or EP between 2007 and 2018 will be evaluated. Main inclusion criteria are ampullary lesions strictly located to the ampulla. This includes adenoma, adenocarcinoma (T1 and T2), neuroendocrine tumors, gastrointestinal stroma tumors and other rare conditions. Exclusion criteria are peri-ampullary lesions, e.g., from the duodenal wall or the head of the pancreas, and interventions for tumor stages higher than T2. The main objective of this study is to analyze rates of complete resection (R0), recurrence and necessity for complementary interventions following EP, SA, and PD. Treatment-quality for each procedure will be defined by morbidity, mortality and complication rates and will be compared between EP, SA, and PD. Secondary objectives include outcome for patients with incomplete resection or initially understated tumors, lesions of the minor papilla, hereditary syndromes, neuroendocrine tumors, mesenchymal lesions, and other rare conditions. Additionally, we will analyze therapy by argon plasma coagulation and radiofrequency ablation. Furthermore, outcome in curative and palliative interventions can be distinguished. Conclusion: The ESAP study will provide evidence for therapeutic algorithms and data for the implementation of guidelines in the treatment of different types of ampullary tumors, including recurrent, or incomplete resected lesions.

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5-25 kg/m2 : HR = 1.94, 95% CI: 1.25-3.03) and women (HR = 2.66, 95% CI: 1.15-6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99-6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52-4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35-14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76-18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14-0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32-0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04-3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

Healthy lifestyle and the risk of pancreatic cancer in the EPIC study.

Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants' shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e-09) and 0.77 (0.72, 0.82; ptrend = 1.7e-15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e-04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.

Socioeconomic Effect of Education on Pancreatic Cancer Risk in Western Europe: An Update on the EPIC Cohorts Study.

BACKGROUND: To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up. METHODS: Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors. RESULTS: A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02-1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05-1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance. CONCLUSIONS: The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems. IMPACT: The results do not support an association between education and risk of pancreatic cancer.

Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study.

The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.