Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach.

BACKGROUND & AIMS: Relatives of patients with pancreatic cancer and persons with certain inherited syndromes are at increased risk for developing pancreatic cancer. We prospectively evaluated the feasibility of screening for pancreatic neoplasia in high-risk individuals. METHODS: Individuals from familial pancreatic cancer kindreds and a patient with Peutz-Jeghers syndrome underwent screening endoscopic ultrasound (EUS). If the EUS was abnormal, EUS-guided fine-needle aspiration, endoscopic retrograde cholangiopancreatography (ERCP), and spiral computed tomography (CT) were performed. Patients with abnormalities suggesting neoplasia had surgery. RESULTS: Thirty-eight patients were studied; 31 (mean age, 58 yr; 42% men) from kindreds with > or =3 affected with pancreatic cancer; 6 from kindreds with 2 affected relatives, 1 was a patient with Peutz-Jeghers syndrome. None had symptoms referable to the pancreas or suggestive of malignancy. Six pancreatic masses were found by EUS: 1 invasive ductal adenocarcinoma, 1 benign intraductal papillary mucinous neoplasm, 2 serous cystadenomas, and 2 nonneoplastic masses. Hence, the diagnostic yield for detecting clinically significant pancreatic neoplasms was 5.3% (2 of 38). The 1 patient with pancreatic cancer was treated and still is alive and disease-free >5 years after surgery. EUS changes similar to those associated with chronic pancreatitis were found, which were more common in patients with a history of regular alcohol intake (P = 0.02), but also occurred in patients who did not consume alcohol. Screening also led to a new diagnosis and treatment of symptomatic upper-gastrointestinal conditions in 18.4% of patients. CONCLUSIONS: EUS-based screening of asymptomatic high-risk individuals can detect prevalent resectable pancreatic neoplasia but false-positive diagnoses also occur.     

Screening for pancreatic cancer in familial high-risk individuals: A systematic review

AIM: To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals (HRIs).METHODS: Studies were identified by searching PubMed, EBSCO, ClinicalTrials.gov and the Cochrane database from database inception to June 2014. We also obtained papers from the reference lists of pertinent studies and systematic reviews. English-language trials and observational studies were searched. The key words used as search terms were “screening” and “surveillance”. Cost-effectiveness, diagnostic rate, survival rate, mortality and adverse events were the outcomes of interest. Age, sex, lifestyle and other confounding factors were also considered. However, anticipating only a few of these studies, we also included observational studies with or without control groups. We also included studies concerning the anxiety associated with pancreatic cancer risk and other psychological changes in familial HRIs. We extracted details on study design, objectives, population characteristics, inclusion criteria, year of enrollment, method of screening, adjusted and unadjusted mortality, cost-effectiveness and adverse events from the included studies. Studies were assessed using the Reporting of Observational studies in Epidemiology (STROBE) checklist.RESULTS: Sixteen studies on pancreatic cancer screening were included. Five studies included control groups, nine were observational studies without control groups, and the other two studies investigated the worry associated with pancreatic cancer risk. We found that pancreatic cancer screening resulted in a high curative resection rate (60% vs 25%, P = 0.011), longer median survival time (14.5 mo vs 4 mo, P < 0.001), and higher 3-year survival rate (20% vs 15.0%, P = 0.624). We also found that familial HRIs had a higher diagnostic rate of pancreatic tumors than controls (34% vs 7.2%, P < 0.001). In patients who underwent regular physical examinations, more stage I pancreatic cancers were observed (19% vs 2.6%, P = 0.001). In addition, endoscopic ultrasonography, which was the main means of detection, diagnosed 64.3% of pancreatic cancers. In comparison, endoscopic retrograde cannulation of the pancreas, magnetic resonance imaging, and computed tomography diagnosed 28.6%, 42.9%, and 21.4%, respectively. For mass lesions, instant surgery was recommended because of the beneficial effects of post-operative chemotherapy. However, in patients with intraductal papillary mucinous neoplasms, we did not find a significant difference in outcome between surgery and follow-up without treatment. Moreover, pancreatic cancer screening in familial HRIs had a greater perceived risk of pancreatic cancer (P < 0.0001), higher levels of anxiety regarding pancreatic cancer (P < 0.0001), and increased economic burden.CONCLUSION: Pancreatic cancer screening in familial HRIs is associated with a higher detection rate and longer survival, although screening may influence psychological function and increase the economic burden.     

Screening for hepatocellular carcinoma in high-risk individuals. A clinical review

Hepatocellular carcinoma occurs primarily in individuals with chronic hepatitis B infection and cirrhosis. This tumor is curable only when diagnosed at an early stage and then surgically resected. Therefore, screening tests have been used to identify small tumors in high-risk patients. Currently, the most sensitive and specific tests available involve measurement of serum alpha-fetoprotein levels and high-resolution ultrasonography. The results of these tests are often complementary in making a diagnosis. To be most cost-effective, the frequency of screening can be adjusted to the degree of risk of hepatocellular carcinoma.     

Baseline osteocalcin levels and incident diabetes in a 3-year prospective study of high-risk individuals

AimExperimental evidence suggests that osteocalcin is a key messenger that affects both adipocytes and insulin-producing β cells. Epidemiological cross-sectional studies have shown a negative association between plasma levels of osteocalcin and glucose. For this reason, the hypothesis that lower baseline osteocalcin plasma levels are associated with diabetes was prospectively tested.MethodsThe study population consisted of individuals at high risk for type 2 diabetes who were screened for participation in the Greek arm of a European type 2 diabetes prevention study (the DE-PLAN study). All participants were free of diabetes at baseline and underwent a second evaluation 3 years later. Diabetes status was defined according to an oral glucose tolerance test.ResultsA total of 307 subjects were included in the present analysis. The population, including 154 men (50.3%), was middle-aged (54.4 ± 10.2 years) and overweight (BMI: 29.5 ± 4.9 kg/m²). At baseline, mean total plasma osteocalcin was lower in those with impaired fasting glucose and/or impaired glucose tolerance compared with those with normal glucose tolerance (6.0 ± 3.1 ng/mL vs. 7.3 ± 4.0 ng/mL, respectively; P = 0.01). After 3 years, 36 subjects had developed diabetes. In the prospective evaluation, there was no association between baseline osteocalcin levels and diabetes (OR: 1.04 per 1 ng/mL, 95% CI: 0.93–1.15; P = 0.49) on multivariable logistic regression analysis, nor was there any correlation with changes in plasma glucose after 3 years (r = 0.09, P = 0.38).ConclusionOur prospective results show that lower levels of circulating osteocalcin do not predict future diabetes development and, in contrast to most cross-sectional published data so far, suggest that this molecule may not be playing a major role in glucose homoeostasis in humans.     

Familial pancreatic cancer and hereditary syndromes: screening strategy for high-risk individuals

Globally, and almost evenly across nations, a familial disposition can be found in 4–10% of patients with pancreatic cancer (PC). A family history of PC is a risk for this disease and the risk level changes in correlation with the number of affected relatives. Several hereditary syndromes with potential germline mutation also have a high risk for PC; however, little is yet known regarding the genes responsible for familial pancreatic cancer (FPC). Characteristics of FPC cases are similar to those of other familial tumors, including younger onset than in sporadic cases and an ethnic difference (Ashkenazi Jewish > other Caucasian). Other risks resemble those of sporadic cases and include smoking and diabetes mellitus. People with several genetic syndromes, including Peutz–Jeghers syndrome, hereditary pancreatitis, breast-ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer, and familial adenomatous polyposis also have an increased risk of PC. In many countries, but not yet in Japan, screening of these high-risk individuals is now ongoing for the detection of early PC under established familial pancreatic cancer registries. In addition to the ordinary risk factors, such as smoking, diabetes, pancreatitis, cysts, duct ectasia, and intraductal papillary mucinous neoplasm (IPMN), individuals with a family history of PC and hereditary syndromes are expected to be entered into the screening protocol.     

Methods and outcomes of screening for pancreatic adenocarcinoma in high-risk individuals

Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasia, for which secondary prevention (i.e., screening) is advisable for high-risk individuals with “familiar pancreatic cancer” and with other specific genetic syndromes (Peutz-Jeghers, p16, BRCA2, PALB and mismatch repair gene mutation carriers). There is limited evidence regarding the accuracy of screening tests, their acceptability, costs and availability, and agreement on whom to treat. Successful target of screening are small resectable PDAC, intraductal papillary mucinous neoplasms with high-grade dysplasia and advanced pancreatic intraepithelial neoplasia. Both magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS) are employed for screening, and the overall yield for pre-malignant or malignant pancreatic lesions is of about 20% with EUS and 14% with MRI/magnetic resonance colangiopancreatography. EUS performs better for solid and MRI for cystic lesions. However, only 2% of these detected lesions can be considered a successful target, and there are insufficient data demonstrating that resection of benign or low grade lesions improves survival. Many patients in the published studies therefore seemed to have received an overtreatment by undergoing surgery. It is crucial to better stratify the risk of malignancy individually, and to better define optimal screening intervals and methods either with computerized tools or molecular biomarkers, possibly in large multicentre studies. At the moment, screening should be carefully performed within research protocols at experienced centres, offering involved individuals medical and psychological advice.     

Screening/surveillance programs for pancreatic cancer in familial high-risk individuals: A systematic review and proportion meta-analysis of screening results

Background/Objectives

Screening/surveillance programs for pancreatic cancer (PC) in familial high-risk individuals (FPC-HRI) have been widely reported, but their merits remain unclear. The data reported so far are heterogeneous—especially in terms of screening yield. We performed a systematic review and meta-analysis of currently available data coming from screening/surveillance programs to evaluate the proportion of screening goal achievement (SGA), overall surgery and unnecessary surgery.

内镜下胰管括约肌切开术后早期并发症的前瞻性研究

目的评价内镜下胰管括约肌切开术后早期并发症的发生率及相关危险因素。方法前瞻性观察2006年5月至2007年4月行ERCP的住院患者,将ERCP下行胰管括约肌切开术的患者纳入研究。在ERCP术前及术中分别将患者和操作相关情况记录在统一的观察表上;术后随访并发症的发生情况直至出院;有关数据进行统计学分析。结果在纳入观察的165例行胰管括约肌切开术的患者中,25例发生并发症（15．2％）,其中急性胰腺炎22例（13．3％,轻度15例、中度6例、重度1例）,出血1例（0．6％）,急性胆管炎2例（1．2％）,无穿孔或操作相关的死亡发生。多变量分析提示术后急性胰腺炎危险因素是：女性（OR=3．8,95％CI1．4～10．8）、复发性胰腺炎（OR=3．1,95％CI1．0-9．9）、副乳头切开术（OR=5．9,95％CI1．2—28．8）。结论与常规ERCP操作比较,内镜下胰管括约肌切开术后急性胰腺炎的发生率较高。特别是女性、复发性胰腺炎、行副乳头切开术的患者,术后更易发生急性胰腺炎。     

Pheochromocytoma in multiple endocrine neoplasia type 2: a prospective study

OBJECTIVE: The aim of this prospective study is to update our knowledge of the chronology of pheochromocytoma occurrence in multiple endocrine neoplasia type 2 (MEN 2), and to better manage MEN 2 patients after the genetic diagnosis. DESIGN: Eighty-seven non-index gene carrier MEN 2 patients were included in this prospective study: 84 patients with MEN 2A (from 52 families) and 3 with MEN 2B (from 3 families). METHODS: Medullary thyroid carcinoma (MTC) was diagnosed by measuring plasma calcitonin in basal conditions or after pentagastrin stimulation. The search for pheochromocytoma consisted of clinical evaluation, 24 h determination of urinary catecholamines and adrenal imaging. The mean age at genetic diagnosis of MEN 2 was 14.0+/-7.0 years, the mean duration for the follow-up was 7.6+/-2.8 years. RESULTS: All 87 patients had a MTC detected at the same time as the genetic diagnosis was made. Urinary catecholamine measurements led to the diagnosis of pheochromocytoma and a combination of imaging techniques enabled the correct localization of both unilateral or bilateral adrenal involvement. Pheochromocytoma was detected simultaneously with MTC in only seven patients, and seven others were detected throughout the follow-up. Of the 14 patients with pheochromocytoma, 11 had bilateral involvement: nine were initially bilateral and two became so during follow-up. CONCLUSION: This study demonstrates that in MEN 2, MTC is the lesion which appears earliest. Pheochromocytoma develops later during the evolution of the disease, and necessitates regular clinical and biological monitoring throughout follow-up. Determination of urinary and/or plasma catecholamines and metanephrines should be performed to detect pheochromocytoma. Imaging techniques lead to the detection of both unilateral and bilateral pheochromocytoma, thus making video-assisted laparoscopic adrenalectomy possible.     

Stepwise radical endoscopic resection is effective for complete removal of Barrett's esophagus with early neoplasia: a prospective study

OBJECTIVES: Endoscopic therapy for early neoplasia in Barrett's esophagus (BE) is evolving rapidly. Aim of this study was to prospectively evaluate safety and efficacy of stepwise radical endoscopic resection (ER) of BE containing early neoplasia. METHODS: Patients with early neoplasia (i.e., high-grade intraepithelial neoplasia or early cancer) in BE < or = 5 cm, without signs of submucosal infiltration or lymph node/distant metastases, were included. Patients underwent resection sessions (cap technique after submucosal lifting) with intervals of 6 wk. RESULTS: Between January 2003 and December 2004, 39 consecutive patients were included. Therapy was discontinued in two patients due to unrelated comorbidity. Complete eradication of early neoplasia was achieved in all 37 treated patients in a median number of three sessions. Complete removal of all Barrett's mucosa was achieved in 33 (89%) patients: 4 patients (all had undergone APC [argon plasma coagulation]) were found to have small isles of Barrett's mucosa underneath neosquamous mucosa. Complications occurred in two out of 88 (2%) ER procedures: one asymptomatic perforation, one delayed bleeding. Symptomatic stenosis occurred in 10 of 39 (26%) patients and was effectively treated by endoscopic bougienage. During a median follow-up of 11 months, no patients died and none had recurrence of neoplasia or Barrett's mucosa. CONCLUSIONS: Stepwise radical ER is effective for selected patients with early neoplasia in BE; provides optimal histopathological diagnosis; and may reduce recurrence rate, since all mucosa at risk is effectively removed. Use of APC should be limited to prevent buried Barrett's mucosa. Methods for prevention of stenosis should be developed.     

Natural course of asymptomatic pancreatic pseudocyst: a prospective study.

AIM: To study the natural course of asymptomatic pseudocysts of the pancreas. METHODS: Thirty patients (age range 18-68 years, mean 44; 24 men) with asymptomatic pseudocysts of the pancreas were enrolled between December 2001 and December 2003, and were followed up every month. Those who developed symptoms due to pseudocyst (increasing pain or features of obstruction such as vomiting or jaundice) were subjected to an endoscopic or surgical drainage procedure. End point of the study was either spontaneous resolution of pseudocyst or drainage procedure. RESULTS: Eighteen (60%) of 30 patients had resolution of the pseudocyst over an average duration of 5 months. Maximum diameter of less than 7.5 cm and cyst volume less than 250 mL were significantly more frequent in patients with resolution of pseudocyst than in those without (14/18 vs 2/12 [p=0.001] and 15/18 vs 2/12 [p=0.0003], respectively). Presence of internal debris was associated with non-resolution (9/12 vs 2/18; p=0.001). CONCLUSION: Pseudocysts with less than 7.5 cm diameter, volume less than 250 mL, and absence of internal debris were associated with spontaneous resolution within an average duration of 5 months.     

Total costs and predictors of costs in individuals with early inflammatory polyarthritis: a community-based prospective study

OBJECTIVE: To estimate the health service, non-health service and total costs and predictors of costs in individuals with early inflammatory polyarthritis (IP). METHODS: We conducted a prospective longitudinal study over a 6-month period. The participants were a random sample of 133 individuals who had enrolled with the community-based Norfolk Arthritis Register (NOAR) database between 1994 and 1999. The main outcome measures were the mean (per person) 6-month health service cost, non-health-service cost and total cost associated with IP. RESULTS: One hundred and fifteen of the 133 individuals who were recruited into the study completed 6 months of follow-up. The mean 6-month total cost was estimated to be 2800 pounds sterling per person, of which 14% was health service costs and the remainder non-health-service costs. Higher total costs were associated with lower health status and rheumatoid factor positivity. CONCLUSIONS: Early IP has a considerable impact on both the health-care system and, more importantly, society. Non-health-service costs (i.e. costs incurred by the individual with the disease, their family and friends) account for a substantial proportion (86%) of the total costs associated with early IP.     

Safety of propofol for conscious sedation during endoscopic procedures in high-risk patients-a prospective,controlled study

OBJECTIVES: Propofol, a rapidly-acting hypnotic agent, is increasingly being used for endoscopic sedation. Serious adverse effects, including respiratory and cardiovascular depression, make many endoscopists reluctant to use propofol in critically ill patients. This study characterizes propofol's safety profile in consecutive high-risk patients (American Society of Anesthesiologists [ASA] classes III and IV) compared with matched subjects (ASA classes I and II). METHODS: During a 19-month period, 1370 at risk-patients were sedated with propofol, of whom 47% (614 ASA III, 28 ASA IV) were age matched with 642 consecutive patients of the same gender and age assigned to ASA classes I and II and undergoing the same endoscopic procedures (395 gastroscopies, 201 colonoscopies, 14 combined). Registered nurses performed all sedations by propofol dose titration while carefully monitoring arterial oxygen saturation, heart rate, and blood pressure. RESULTS: No major complications occurred among the critically ill patients. There was, however, an increased risk for a short relevant oxygen desaturation (<90%) of 3.6% for ASA III and IV versus 1.7% for ASA I and II (p = 0.036). In four versus one case, short mask ventilation was necessary. Also, a greater proportion of patients showed a > or =5% oxygen saturation decrease. There was no pronounced influence on arterial pressure or heart rate and no perforations in 336 colonoscopies. CONCLUSIONS: With careful monitoring, propofol sedation during GI endoscopies is safe, even for high-risk patients. Considering their higher comorbidity and tendency toward oxygen desaturation, they need particularly careful monitoring, and the required dose is, on mean, 10-20% lower than in ASA classes I and II.     

Surveillance of high-risk individuals for pancreatic cancer with EUS and MRI: A meta-analysis

Background/objectivesConsensus guidelines recommend surveillance of high-risk individuals (HRIs) for pancreatic cancer (PC) using endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI). This study aims to assess the yield of PC surveillance programs of HRIs and compare the detection of high-grade dysplasia or T1N0M0 adenocarcinoma by EUS and MRI.MethodsThe MEDLINE and Embase (Ovid) databases were searched for prospective studies published up to April 11, 2019 using EUS and/or MRI to screen HRIs for PC. Baseline detection of focal pancreatic abnormalities, cystic lesions, solid lesions, high-grade dysplasia or T1N0M0 adenocarcinoma, and all pancreatic adenocarcinoma were recorded. Weighted pooled proportions of outcomes detected were compared between EUS and MRI using random effects modeling.ResultsA total of 1097 studies were reviewed and 24 were included, representing 2112 HRIs who underwent imaging. The weighted pooled proportion of focal pancreatic abnormalities detected by baseline EUS (0.34, 95% CI 0.30–0.37) was significantly higher (p = 0.006) than by MRI (0.31, 95% CI 0.28–0.33). There were no significant differences between EUS and MRI in detection of other outcomes. The overall weighted pooled proportion of patients with high-grade dysplasia or T1N0M0 adenocarcinoma detected at baseline (regardless of imaging modality) was 0.0090 (95% CI 0.0022–0.016), corresponding to a number-needed-to-screen (NNS) of 111 patients to detect one high-grade dysplasia or T1N0M0 adenocarcinoma.ConclusionsSurveillance programs are successful in detecting high-risk precursor lesions. No differences between EUS and MRI were noted in the detection of high-grade dysplasia or T1N0M0 adenocarcinoma, supporting the use of either imaging modality.     

Screening for early detection of cardiovascular disease in asymptomatic individuals

Objective

Primary prevention of cardiovascular disease has been aimed at risk factor identification and treatment without efforts to document early cardiovascular disease. The objective of the current study is to screen individuals with vascular and cardiac tests aimed at identifying early abnormalities likely to progress and to measure risk contributors susceptible to therapy.

Methods

A center was established for comprehensive screening of an asymptomatic population with 10 tests designed to detect early vascular and cardiac abnormalities and blood tests to identify potential targets for risk contributor intervention. The first 396 individuals screened in the center have been analyzed.

Results

Using a scoring system from 0 (no disease) to 20 (advanced disease), 49% of the population exhibited scores of ≥5 and 39% exhibited scores of ≥6. These scores appear indicative of early disease mandating initiation of or change in medical therapy, which was recommended to the individuals screened and to their primary care physicians.

Conclusion

The screening tests utilized are effective in uncovering unsuspected early cardiovascular disease in which targeted treatment could be effective in reducing the incidence of cardiovascular events in susceptible individuals. Documentation of the sensitivity and specificity of this approach requires longitudinal study.     

Fever of unknown origin in uremic patients: a controlled prospective study.

Twenty-nine uremic patients with fever of unknown origin (FUO) admitted to our clinic between 1994 and 1998 were evaluated prospectively. A group of 50 consecutive non-uremic patients with FUO followed up during the same period was used for comparison. The causes of FUO found in the uremic and non-uremic groups, respectively were as follows: infectious diseases, 69 vs. 44% (p = 0.03); collagen vascular diseases, 6.9 vs. 6%; neoplasms, 3.4 vs. 26%; miscellaneous causes, 3.4 vs. 16%; and undiagnosed, 17.2 vs. 8%. Tuberculosis was the most common cause of FUO in both groups. The spectrum of underlying conditions for FUO in our uremic patients differed from that in the non-uremic patients and the uremic patients had a very high propensity for infectious diseases, especially tuberculosis.