Current Practices and Novel Techniques in the Diagnosis and Management of Neuroendocrine Tumors of Unknown Primary Neuroendocrine tumors (NETs) comprise a heterogeneous group of neoplasms in which tumor staging/prognosis and response to treatments depend heavily on accurate and timely identification of the anatomic primary site or NET subtype. Despite recent technological advancements and use of multiple diagnostic modalities, 10% to 14% of newly diagnosed NETs are not fully characterized based on subtype or anatomic primary site. Inability to fully characterize NETs of unknown primary may cause delays in surgical intervention and limit potential treatment options. To address this unmet need, clinical validity and utility are being demonstrated for novel approaches that improve NET subtype or anatomic primary site identification. Functional imaging using 68Ga-radiolabeled DOTATATE positron emission tomography/computed tomography has been shown to overcome some false-positive and resolution issues associated with octreotide scanning and computed tomography/magnetic resonance imaging. Using a genomic approach, molecular tumor classification based on differential gene expression has demonstrated high diagnostic accuracy in blinded validation studies of different NET types and subtypes. Given the widespread availability of these technologies, we propose an algorithm for the workup of NETs of unknown primary that integrates these approaches. Including these technologies in the standard workup will lead to better NET subtype identification and improved treatment optimization for patients.

Vasoactive Intestinal Peptide–Secreting Tumors: A Review Vasoactive intestinal peptide–secreting tumors (VIPomas) are a group of rare neuroendocrine tumors, which cause a typical syndrome of watery diarrhea. Most of these tumors are found in the pancreas and are usually detected at a later stage. Although curative resection is not possible in most of these tumors, both symptom and tumor control can be achieved by a multidimensional approach, to enable a long survival of most patients. There are no clear-cut guidelines for the management of VIPomas because of the rarity of this neoplasm and lack of prospective data. In this review, we discuss the available evidence on the clinical features and management of these rare tumors.

Analysis of Real-World Treatment Patterns, Healthcare Resource Utilization, and Costs Between Octreotide and Lanreotide Among Patients With Neuroendocrine Tumors Objective The aim of the study was to assess treatment patterns, healthcare resource utilization, and healthcare costs among patients with neuroendocrine tumors (NETs) receiving long-acting octreotide versus lanreotide, overall and in patients with carcinoid syndrome (CS). Methods A provider-based claims database was used to identify NET patients who first initiated long-acting octreotide or lanreotide (index date) from January 2015 to November 2017. Propensity-score matching 1:1 was used. Patients with CS were identified from the previously mentioned matched cohorts. Time-to-treatment discontinuation (TTD) was estimated using Kaplan-Meier analyses. Per-patient-per-month rates of healthcare resource utilization were compared using rate ratios from multivariable Poisson regression models. Multivariable linear regression models were used to compare mean monthly cost differences. Results The median TTD was similar between the 2 matched cohorts (N = 543 each; long-acting octreotide = 19.2 months, lanreotide = 17.5 months, P = 0.58). Significantly fewer NET-related outpatient visits (rate ratio = 0.95, P = 0.005) and significantly lower total healthcare costs (mean monthly cost difference: all-cause = US −$3701, NET-related = US −$3752, Ps < 0.001) were observed in the long-acting octreotide cohort than lanreotide. Similar results were found in CS patients. Conclusions Patients on first-line long-acting octreotide and lanreotide had similar TTD. Long-acting octreotide was associated with significantly lower total healthcare costs than lanreotide.

Acupuncture for Acute Pancreatitis: A Systematic Review and Meta-analysis Objective The objective of this study was to assess the efficacy and safety of acupuncture plus routine treatment (RT) for acute pancreatitis (AP). Methods Literature searches were performed in 8 databases up to October 31, 2018. Randomized controlled trials comparing acupuncture plus RT with RT alone for AP were included. Results Twelve eligible studies were included finally. The meta-analysis showed that acupuncture plus RT compared with RT alone could significantly improve the total effective rate and gastrointestinal function and reduce the Acute Physiology, Age, Chronic Health Evaluation II score, tumor necrosis factor α count, the time of resuming to diets, and the length of hospital stay. Only 3 of the studies reported adverse events or reactions. Conclusions This study suggested that acupuncture combined with RT may be effective for AP. However, more rigorously designed randomized controlled trials are warranted to confirm the current findings.

Parecoxib Improves the Outcomes of Acute Mild and Moderate Pancreatitis: A 3-Year Matched Cohort Study Based on a Prospective Database Objectives The aim of this study was to evaluate the role of parecoxib in patients with different severities of acute pancreatitis (AP). Methods A total of 772 eligible patients with AP were divided into 4 groups: mild and moderately AP (MAP) treated with parecoxib (group A, n = 236), MAP without parecoxib treatment (group B, n = 453), severe AP (SAP) treated with parecoxib (group C, n = 28), and SAP without parecoxib treatment (group D, n = 55). Patients in group A were exactly matched with patients in group B by propensity score matching, similar to the matching between group C and group D. Results The morbidity of abdominal infection in group A was significantly lower as compared with that in group B (P < 0.050). The progression of MAP to SAP significantly decreased in group A than group B (P < 0.050). No significant differences were observed between group C and group D. The risk factors independently related to the progression of MAP included alcoholic/high-fat dietary (P = 0.028) and parecoxib administration (P = 0.011). Conclusions Early administration of parecoxib could reduce the morbidity of complications among patients with MAP. Parecoxib may prevent the progression of MAP to SAP and improve its outcomes.

Secondhand Smoke Exposure and Serum Trypsinogen in Cystic Fibrosis Carriers Objective The objective of this study was to determine if infants carrying 1 cystic fibrosis transmembrane receptor (CFTR) mutation demonstrate pancreatic inflammation in response to tobacco exposure. Methods Cystic fibrosis carrier infants aged 4 to 16 weeks were prospectively enrolled. Tobacco exposure was assessed by survey and maternal hair nicotine analysis. Serum immunoreactive trypsinogen (IRT) levels at birth and at the time of recruitment were analyzed relative to the presence or absence of tobacco exposure. The effect of the severity of the CFTR mutation carried by the infant on the tobacco-IRT relationship was also analyzed. Results Forty-eight infants completed the study. Newborn screen and follow-up IRT levels were not different between exposed infants (19 by hair analysis) and nonexposed infants (29 by hair analysis). Follow-up IRT levels were lower in infants with more severe CFTR mutations (P = 0.005). There was no difference in follow-up IRT based on CFTR mutation severity in exposed infants. Nonexposed infants with milder CFTR mutations had higher median IRT values on follow-up testing than those with more severe CFTR mutations (P < 0.05). Conclusions The pancreas of cystic fibrosis carrier infants is affected by tobacco exposure, and those carrying less severe CFTR mutations may be more susceptible to tobacco effects.

Risk Factors Associated With Progression Toward Endocrine Insufficiency in Chronic Pancreatitis Objective Little data exist describing the change over time in islet function and glycemic control in patients with chronic pancreatitis (CP). Methods In 325 CP patients who underwent 2 mixed meal tolerance tests and/or glycated hemoglobin (HbA1c) levels, we estimated the rate of change in metabolic measures per 6 months and assessed the association between potential risk factors for diabetes and rate of change using multivariate regression models. Results Per 6-month time, HbA1c increased by 0.062% with a standard error of 0.029% (P = 0.037) and the ratio (area under the curve (AUC) C-peptide to AUC glucose from mixed meal tolerance testing) decreased by 0.0028 with a standard error of 0.0011 (P = 0.014). We observed more rapid decline in smokers (AUC C-peptide, P = 0.043) and patients with surgical drainage (AUC glucose, P = 0.001; ratio, P = 0.03) or with calcific pancreatitis (HbA1c, P = 0.003). In multivariate models, AUC C-peptide and ratio declined at a greater rate in smokers and HbA1c in those with pancreatic calcifications (both P < 0.05). Conclusions We observed a measurable decline in β-cell function and glycemic control in patients with CP. Patients with a history of tobacco smoking, surgical drainage, or pancreatic calcification may be at highest risk.

What is the Outcome of Patients Affected by Intraductal Papillary Mucinous Neoplasms Without High-Risk Stigmata?: A Single-Center Retrospective Study Objectives The objectives of the study were to define the natural history of intraductal papillary mucinous neoplasms (IPMNs) without high-risk stigmata (HRS) and to identify factors capable of influencing outcome and management. Methods This is a retrospective study of patients affected by IPMNs without HRS. Survival analyses included overall survival, disease-specific survival, and years of life lost. Uni- and multivariate analyses were carried out to identify factors capable of predicting years of life lost. Results Three hundred fifty-six patients were analyzed. Fifty-three patients (14.9%) died: no postoperative mortality, 6 (1.7%) patients from pancreatic cancer and 47 (13.2%) from reasons not related to the disease. Mean overall survival and disease-specific survival were 199.4 (SD, 16.6) and 281 months (SD, 6.9), respectively. The years of life lost of the sample observed with respect to the general population were 2 years and 3 months (15 years and 3 months vs 17 years and 6 months). Younger age, length of follow-up more than 3 years, and surgery significantly increased the years of life lost. Conclusions The patients affected by IPMNs without HRS rarely died from the disease. Young age (<65 years) and follow-up more than 3 years seemed to be the only factors capable of influencing the outcome and management.

Lowest Case Fatality Rate for Patients With Acute Pancreatitis Admitted in Gastroenterology Units in Veneto Region, Italy Objectives This study aimed to evaluate trends in hospitalizations and outcomes of acute pancreatitis (AP) according to first admitting hospital unit and hospital volumes. Methods Hospital discharge records of patients with AP admitted in the Veneto Region (Northeast Italy) during the period 2001–2015 were examined. Results A total of 23,389 patients (54% males; mean age, 62.2 years; standard deviation, 19.3 years) were admitted for AP. Both hospitalization (32.4 to 29.5/100,000 inhabitants per year; P < 0.05) and in-hospital mortality (1.41 to 0.79/100,000 inhabitants per year; P < 0.05) decreased over the study period. Case fatality rate was altogether 3.2%. The percentages of patients admitted in surgery, nongastroenterology medical units, gastroenterology, and intensive care were 52%, 30%, 16%, and 2%, respectively. Fewer fatalities were observed in gastroenterology units (1.7%) compared with nongastroenterology medical units (4.3%; odds ratio, 0.37; 95% confidence interval, 0.28–0.49) and surgical units (2.7%; odds ratio, 0.61; 95% confidence interval, 0.47–0.80). Fatalities decreased progressively with increasing hospital volumes from 3.7% to 2.9% (P < 0.05). Conclusion In the Veneto Region, both hospitalizations and in-hospital mortality for AP significantly decreased over the last 15 years. Case fatality rate was lowest for patients admitted in gastroenterology units.

Long-Term Functional Outcome After Pancreatoduodenectomy for Periampullary Carcinoma With Morphological Correlation Objective The aim of the study was to evaluate the long-term functional outcome (exocrine and endocrine) and morphological changes in remnant pancreas after pancreatoduodenectomy and its clinical impact. Methods Periampullary carcinoma patients with minimum follow-up of 2 years and without recurrence were included (N = 102). Exocrine insufficiency includes clinical steatorrhea and fecal elastase-1 (FE-1) levels; endocrine insufficiency, glucose levels and glycated hemoglobin; and morphological changes, main pancreatic duct (MPD) diameter and thickness of remnant pancreas. Results The mean (standard deviation) follow-up period was 59 (26) months. Of the 102 patients, 81 (80%) had severely deficient FE-1 (0–100 μg/g). The preoperative MPD was significantly more and thickness of remnant pancreas was significantly less in patients with severely deficient FE-1. Overall, 15.6% (16/102) developed steatorrhea and improved on enzyme replacement therapy. The presence of MPD stricture (P = 0.008) and weight loss (P = 0.001) were significantly associated with steatorrhea. New-onset diabetes was seen in 17% (15/90) patients, of whom 3 of 5 developed it after 4 years (range, 4–7 years). The blood glucose was controlled on oral hypoglycemics in 2 (10/15) of 3 patients. Conclusions The assessment by FE-1 indicates loss of exocrine function in more than 90%, whereas only 1 of 6 developed steatorrhea and new-onset diabetes. Morphological changes especially MPD stricture affect the functional status of remnant pancreas.