Abdominal ultrasound in the characterization of branch-duct intraductal papillary mucinous neoplasms: A new tool for surveillance of low-risk patients?

BACKGROUND: Magnetic resonance imaging (MRI) is regarded as gold-standard for intraductal papillary mucinous neoplasms (IPMNs) follow-up. Given the low risk of transformation and the increasing population under surveillance, there is growing interest in identifying optimal follow-up strategies. AIM: To evaluate reliability of abdominal ultrasound (US) for characterization of low-risk IPMN, compared to MRI. METHODS: Prospective monocentric study among 79 consecutive patients with a suspected BD-IPMN on US. Each patient underwent confirmatory MRI. We evaluated Cohen's kappa statistic and concordance rate (CR) between MRI and US. RESULTS: Of 79 suspected IPMNs on US, MRI confirmed 71 BD-IPMNs. There was high agreement for cyst location and number (CR and kappa of 77.5 % and 81.7 % and 0.66±0.08 and 0.62±0.11 respectively). We found high agreement for cyst size (CR=96.5 %, kappa=0.93±0.05) and main pancreatic duct (MPD) dilatation (CR=100 %, kappa=1). There was a good agreement for thickened septa (CR=80.3 %, kappa=0.38±0.12). US seems inferior to MRI for the identification of mural nodules < 5 mm (CR=97.2 %, kappa=0). CONCLUSIONS: In a cohort of low-risk BD-IPMN, US presented high agreement rate with MRI regarding location, number, and size. There was a good agreement for MPD dilatation and thickened septa, while US underperform for detection of mural nodules < 5 mm.

Evolving knowledge in surgical oncology of pancreatic cancer: from theory to clinical practice-a fifteen-year journey at a tertiary referral centre.

Pancreatic ductal adenocarcinoma (PDAC) is an increasing disease having a poor prognosis. The aim of the present study was to evaluate the effect of different models of care for pancreatic cancer in a tertiary referral centre in the period 2006-2020. Retrospective study of patients with PDAC observed from January 2006 to December 2020. The demographic and clinical data, and data regarding the imaging techniques used, preoperative staging, management, survival and multidisciplinary tumour board (MDTB) evaluation were collected and compared in three different periods characterised by different organisation of pancreatic cancer services: period A (2006-2010); period B (2011-2015) and period C (2016-2020). One thousand four hundred seven patients were analysed: 441(31.3%) in period A; 413 (29.4%) in B and 553 (39.3%) in C. The proportion of patients increased significantly, from 31.3% to 39.3% (P = 0.032). Body mass index (P = 0.033), comorbidity rate (P = 0.002) and Karnofsky performance status (P < 0.001) showed significant differences. Computed tomography scans (P < 0.001), endoscopic ultrasound (P < 0.001), fine needle aspiration, fine needle biopsy (P < 0.001), and fluorodeoxyglucose-positron emission tomography/computed tomography (P < 0.001) increased; contrast-enhanced ultrasound (P = 0.028) decreased. The cTNM was significantly different (P < 0.001). The MDTB evaluation increased significantly (P < 0.001). Up-front surgery and exploratory laparotomy decreased (P < 0.001), neoadjuvant treatment increased (P < 0.001). The present study showed the evolving knowledge in surgical oncology of pancreatic cancer at a tertiary referral centre over the time. The different models of care of pancreatic cancer, in particular the introduction of the MDTB and the institution of a pancreas unit to the decision-making process seemed to be influential.

Adherence to Guidelines Influenced the Mortality, Hospital Stay, and Health Care System Costs in Patients With Acute Pancreatitis.

OBJECTIVES: The primary end point was the compliance rate with guidelines. The secondaries were mortality, hospital stay, and costs. METHODS: This study included 1904 patients with acute pancreatitis (AP): group A, diagnosed before 2013, and group B, after 2013. RESULTS: The compliance rate was 0.6%. The compliance rates increased for fluid resuscitation (3.3% vs 13.7%, P < 0.001), for antibiotics use (21.9% vs 28.1%, P = 0.002), for oral feeding (55.0% vs 49.7%, P = 0.007), and for correct use of endoscopic retrograde cholangiopancreatography (ERCP) (83% vs 91.9%, P < 0.001). Compliance to severity assessment with computed tomography (odds ratio [OR], 0.4; P = 0.029), parenteral nutrition recommendations (OR, 0.3; P = 0.009), and early surgery (OR, 0.3; P = 0.010) reduced the mortality. Compliance to antibiotic therapy (OR, 0.6; P < 0.001), correct use of parenteral nutrition (OR, 0.3; P < 0.001), correct use of ERCP (OR, 0.5; P < 0.001), and early surgery (OR, 0.3; P = 0.010) reduced hospital stay. The compliance reduced the costs for parenteral nutrition (P < 0.001), correct use of ERCP (P = 0.011), and surgery (P = 0.010). CONCLUSIONS: The adherence to guidelines for AP was low. Compliance could reduce mortality, prolonged hospital stay, and costs.

External validation of nomogram for predicting malignant intraductal papillary mucinous neoplasm (IPMN): from the theory to the clinical practice using the decision curve analysis model.

The management of IPMNs is a challenging and controversial issue because the risk of malignancy is difficult to predict. The present study aimed to assess the clinical usefulness of two preoperative nomograms for predicting malignancy of IPMNs allowing their proper management. Retrospective study of patients affected by IPMNs. Two nomograms, regarding main (MD) and branch duct (BD) IPMN, respectively, were evaluated. Only patients who underwent pancreatic resection were collected to test the nomograms because a pathological diagnosis was available. The analysis included: 1-logistic regression analysis to calibrate the nomograms; 2-decision curve analysis (DCA) to test the nomograms concerning their clinical usefulness. 98 patients underwent pancreatic resection. The logistic regression showed that, increasing the score of both the MD-IPMN and BD-IPMN nomograms, significantly increases the probability of IPMN high grade or invasive carcinoma (P = 0.029 and P = 0.033, respectively). DCA of MD-IPMN nomogram showed that there were no net benefits with respect to surgical resection in all cases. DCA of BD-IPMN nomogram, showed a net benefit only for threshold probability between 40 and 60%. For these values, useless pancreatic resection should be avoided in 14.8%. The two nomograms allowed a reliable assessment of the malignancy rate. Their clinical usefulness is limited to BD-IPMN with threshold probability of malignancy of 40-60%, in which the patients can be selected better than the "treat all" strategy.

Treatment for Infected Pancreatic Necrosis Should be Delayed, Possibly Avoiding an Open Surgical Approach: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To evaluate all invasive treatments for suspected IPN. SUMMARY OF BACKGROUND DATA: The optimal invasive treatment for suspected IPN remains unclear. METHODS: A systematic search of randomized clinical trials comparing at least 2 invasive strategies for the treatment of suspected IPN was carried out. A frequentist random-effects network meta-analysis was made reporting the surface under the cumulative ranking (SUCRA). The primary endpoint regarded both the in-hospital mortality and major morbidity rates. The secondary endpoints were mortality, length of stay, intensive care unit stay, the pancreatic fistula rate, and exocrine and endocrine insufficiency. RESULTS: Seven studies were included, involving 400 patients clustered as following: 64 (16%) in early surgical debridement (ED); 27 (6.7%) in peritoneal lavage (PL); 45 (11.3%) in delayed surgical debridement (DD), 169 (42.3%) in the step-up approach with minimally invasive debridement (SUA-DD) and 95 (23.7%) with endoscopic debridement (SUA-EnD). The step-up approach with endoscopic debridement had the highest probability of being the safest approach (SUCRA 87.1%), followed by SUA-DD (SUCRA 59.5%); DD, ED, and PL had the lowest probability of being safe (SUCRA values 27.6%, 31.4%, and 44.4%, respectively). Analysis of the secondary endpoints confirmed the superiority of SUA-EnD regarding length of stay, intensive care unit stay, pancreatic fistula rate, and new-onset diabetes. The SUA approaches are similar regarding exocrine function. Mortality was reduced by any delayed approaches (DD, SUA-DD, or SUA-EnD). CONCLUSIONS: The first choice for suspected IPN seemed to be SUA-EnD. An alternative could be SUA-DD. PL, ED, and DD should be avoided.

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.

Prevalence of Asymptomatic Intraductal Papillary Mucinous Neoplasms in Healthy and Ill Populations Detected by Ultrasonography: A Single-Center Study of 6353 Outpatients.

OBJECTIVES: The aim of this study was to establish the prevalence of intraductal papillary mucinous neoplasms (IPMNs) without and with high-risk stigmata (HRS)/worrisome features (WF) and the epidemiologic association between IPMNs and other diseases. METHODS: Ultrasound examinations of outpatients were evaluated. The IPMN was confirmed by magnetic resonance imaging. The prevalence of IPMNs and HRS/WF IPMNs was calculated. The association between IPMNs and other diseases was studied. RESULTS: The prevalence rate of IPMNs was 3.4%. A total of 1,531,264 IPMNs were expected in Italian population (2.5%), whereas 2257 per 100,000 citizens (2.3%) were expected in the European standard population (ESP2013). The prevalence rates of HRS/WF IPMNs were 0.5%, 0.7%, and 0.6%, in our, the Italian, and the ESP2013 populations, respectively. A total of 432,881 and 620 HRS/WF IPMNs per 100,000 residents were expected in the Italian and the ESP2013 populations, respectively. The IPMN prevalence increased over 50 years of age (odds ratio [OR], 3.2; P < 0.001) and over 70 years of age (OR, 1.9; P < 0.001). Female sex was related to the presence of IPMNs (OR, 1.9; P < 0.001). CONCLUSIONS: Intraductal papillary mucinous neoplasms had a high prevalence in asymptomatic nonhospitalized populations. Age older than 50 years identified a possible risk category.

Comparison of Efficacy and Safety of 4 Combinations of Laparoscopic and Intraoperative Techniques for Management of Gallstone Disease With Biliary Duct Calculi: A Systematic Review and Network Meta-analysis.

Importance: Several techniques are used for surgical treatment of gallstone disease with biliary duct calculi, but the safety and efficacy of these approaches have not been compared. Objectives: To compare the efficacy and safety of 4 surgical approaches to gallstone disease with biliary duct calculi. Data Sources: MEDLINE, Scopus, and ISI-Web of Science databases, articles published between 1950 and 2017 and searched from August 12, 2017, to September 14, 2017. Search terms used were LCBDE, LC, preoperative, ERCP, postoperative, period, cholangiopancreatography, endoscopic, retrograde, rendezvous, intraoperative, one-stage, two-stage, single-stage, gallstone, gallstones, calculi, stone, therapy, treatment, therapeutics, surgery, surgical, procedures, clinical trials as topic, random, and allocation in several logical combinations. Study Selection: Randomized clinical trials comparing at least 2 of the following strategies: preoperative endoscopic retrograde cholangiopancreatography (PreERCP) plus laparoscopic cholecystectomy (LC); LC with laparoscopic common bile duct exploration (LCDBE); LC plus intraoperative endoscopic retrograde cholangiopancreatography (IntraERCP); and LC plus postoperative ERCP (PostERCP). Data Extraction and Synthesis: A frequentist random-effects network meta-analysis was performed. The surface under the cumulative ranking curve (SUCRA) was used to show the probability that each approach would be the best for each outcome. Main Outcomes and Measures: Primary outcomes were the safety to efficacy ratio using overall mortality and morbidity rates as the main indicators of safety and the success rate as an indicator of efficacy. Secondary outcomes were acute pancreatitis, biliary leak, overall bleeding, operative time, length of hospital stay, total cost, and readmission rate. Results: The 20 trials comprised 2489 patients (and 2489 procedures). Laparoscopic cholecystectomy plus IntraERCP had the highest probability of being the most successful (SUCRA, 87.2%) and safest (SUCRA, 69.7%) with respect to morbidity. All approaches had similar results regarding overall mortality. Laparoscopic cholecystectomy plus LCBDE was the most successful for avoiding overall bleeding (SUCRA, 83.3%) and for the shortest operative time (SUCRA, 90.2%) and least total cost (SUCRA, 98.9%). Laparoscopic cholecystectomy plus IntraERCP was the best approach for length of hospital stay (SUCRA, 92.7%). Inconsistency was found in operative time (indirect estimate, 19.05; 95% CI, 2.44-35.66; P = .02) and total cost (indirect estimate, 17.06; 95% CI, 3.56-107.21; P = .04). Heterogeneity was observed for success rate (τ, 0.8), operative time (τ, >1), length of stay (τ, >1), and total cost (τ, >1). Conclusions and Relevance: The combined LC and IntraERCP approach had the greatest odds to be the safest and appears to be the most successful. Laparoscopic cholecystectomy plus LBCDE appears to reduce the risk of acute pancreatitis but may be associated with a higher risk of biliary leak.

Impact of surgery and surveillance in the management of branch duct intraductal papillary mucinous neoplasms of the pancreas according to Fukuoka guidelines: the Bologna experience.

The objective of the study was to evaluate the Fukuoka guidelines in indicating the proper management for recognising the risk factors of malignancy. Data of patients with branch duct intraductal papillary mucinous neoplasms who underwent pancreatic resection or surveillance according to the Fukuoka risk parameters were collected in a prospective database. The clinical outcome (development of pancreatic cancer, overall and disease-specific survival) and pathological results were evaluated in all patients and in resected cases, respectively. The data of 197 patients were collected: 23 primarily resected and 174 primarily followed. Of the latter, 16 were secondarily resected. Among the patients resected, 21 (53.9%) showed diagnosis of in situ or invasive carcinoma and only contrast-enhancing mural nodules were significantly related to malignancy (P = 0.002), with a DOR of 3.3 and an LH+ of 2.2. Development of pancreatic cancer was shown in ten (5.7%) of the patients primarily followed. The overall survival and disease-specific survival were similar between patients primarily followed and primarily resected. It seems reasonable to suggest that a branch duct intraductal papillary mucinous neoplasm should be treated as a benign and indolent disease that is rarely malignant. Enhancing mural nodules represent the best indicator for surgery.

Risk Factors for Malignancy of Branch-Duct Intraductal Papillary Mucinous Neoplasms: A Critical Evaluation of the Fukuoka Guidelines With a Systematic Review and Meta-analysis.

OBJECTIVES: This study aimed to evaluate the accuracy of the risk factors proposed by Fukuoka guidelines in detecting malignancy of branch-duct intraductal papillary mucinous neoplasms. METHOD: Diagnostic meta-analysis of cohort studies. A systematic literature search was conducted using MEDLINE, the Cochrane Library, Scopus, and the ISI-Web of Science databases to identify all studies published up to 2014. RESULTS: Twenty-five studies (2025 patients) were suitable for the meta-analysis. The "high risk stigmata" showed the highest pooled diagnostic odds ratio (jaundice, 6.3; positive citology, 5.5; mural nodules, 4.8) together with 2 "worrisome features" (thickened/enhancing walls, 4.2; duct dilatation, 4.0) and 1 "other parameters" (carbohydrate antigen 19-9 serum levels, 4.6). CONCLUSIONS: An "ideal risk factor" capable of recognizing all malignant branch-duct intraductal papillary mucinous neoplasms was not identified and some "dismal areas" remain. However, "high risk stigmata" were strongly related to malignancy, mainly enhancing mural nodules. Among the "worrisome features," duct dilatation and thickened/enhancing walls were underestimated, and their diagnostic performance was similar to those of "high risk stigmata." The carbohydrate antigen 19-9 serum level should be added to the Fukuoka algorithm because this value could help in carrying out correct management.

A 5-year experience of benign pancreatic hyperenzymemia.

OBJECTIVE: Benign pancreatic hyperenzymemia is characterized by a long-term increase of serum pancreatic enzymes in otherwise healthy subjects. This study was designed to determine (a) whether all pancreatic enzymes are elevated, (b) the extent of each enzyme increase, (c) the relative frequency of the familial form, and (d) the relative frequencies of pancreatic and salivary hyperamylasemia and macroamylasemia. METHODS: Two hundred seven asymptomatic subjects with benign pancreatic hyperenzymemia were studied during the 5-year period. Serum amylase, isoamylase, and lipase levels were assessed by immunoenzymatic assays. RESULTS: Most (n = 183; 88.4%) patients had benign pancreatic hyperenzymemia; 155 (74.9%) patients had an abnormal increase of all 3 enzymes, 15 (7.2%) patients of only lipase, and 13 (6.3%) patients of only amylase and pancreatic isoamylase. Lipase levels were the highest (1.1-21 times above upper limit). Of the 183 subjects, 72 were members of 35 different families, 15 (7.2%) had increased salivary amylase, and 9 (4.3%) had macroamylasemia. Wide day-to-day fluctuations of pancreatic enzymes, including falls within the reference ranges, were recorded. CONCLUSIONS: All enzymes were increased in benign pancreatic hyperenzymemia, with lipase showing the highest elevation. Doctors should reassure patients about the benign nature of this condition and limit repeating useless examinations.

A study of pancreatic function among subjects over ninety years of age.

BACKGROUND: Among the various studies of pancreatic function in the elderly published so far, none have dealt with subjects over 90 years of age. The aim of this study was to examine pancreatic function in healthy individuals over 90 years old. METHODS: Sixty-eight healthy noninstitutionalized elderly persons, aged 91-104 years, with a mean age of 95 years, and 63 younger controls were studied. Pancreatic function was studied by determining fecal elastase 1 concentration. In addition to this test, we also measured serum amylase, pancreatic isoamylase and lipase in 53 of the 68 elderly subjects. RESULTS: All but 1 of the 68 elderly subjects had normal elastase 1 values; the one who did not had a value slightly below normal. No significant difference with controls was found. Serum pancreatic enzymes were normal in almost all of the 53 elderly studied; 3 had a mild elevation only of amylase and 1 had a persistent elevation of amylase, pancreatic isoamylase and lipase. CONCLUSIONS: In subjects over 90 years of age, exocrine pancreatic function continues to be normal; if an impairment occurs, it is mild and not significant for digestion of food. In addition, serum pancreatic enzymes remain within normal limits in the vast majority of cases.

Magnetic resonance cholangiopancreatography in asymptomatic pancreatic hyperenzymemia.

OBJECTIVES: To determine the type and frequency of pancreatic lesions detected by magnetic resonance cholangiopancreatography (MRCP) in subjects with asymptomatic pancreatic hyperenzymemia and to assess for a possible relationship between these lesions and the hyperenzymemia. METHODS: From January 2005 to May 2008, 63 subjects with asymptomatic pancreatic hyperenzymemia were studied by MRCP. In addition, amylase, pancreatic isoamylase, and lipase were determined for 5 consecutive days. RESULTS: In most subjects (n = 57, 90.5%), MRCP showed a normal pancreas. In the remaining 6 subjects (9.5%), the following alterations were found: pancreas divisum in 2, small intrapancreatic cyst in 2, anatomic variant of the Wirsung in 1, and mild dilatation of 3 secondary ducts in 1. In these 6 subjects, hyperenzymemia was highly variable from day to day, with frequent normalizations, as was also true for the 30 subjects with no MRCP alterations in whom diurnal enzyme determinations were made. CONCLUSIONS: Most of the subjects with asymptomatic pancreatic hyperenzymemia did not have pancreatic lesions detectable by MRCP. In the few subjects in whom a lesion was found, the great variability and the frequent transient normalization of serum enzyme levels tend to exclude a relation between the lesion and the hyperenzymemia.

[Benign pancreatic hyperenzynemia or Gullo's syndrome]. / Iperenzimemia pancreatica benigna o sindrome di Gullo.

Benign pancreatic hyperenzymemia is a newly identified syndrome characterized by abnormal increase in serum pancreatic enzymes in absence of pancreatic disease. The hyperenzymemia can occur sporadically or in a familial form, and all of the pancreatic enzymes show elevations. Although the condition is persistent, the enzyme elevations fluctuate considerably, even temporarily returning to normal levels at times. In this paper the main characteristics of this syndrome are described.

SPINK1 and PRSS1 mutations in benign pancreatic hyperenzymemia.

UNLABELLED: The aim of this study was to determine whether mutations in SPINK1/PRSS1 genes are associated with benign pancreatic hyperenzymemia (BPH). METHODS: Sixty-eight subjects with BPH (including 13 familial cases) were studied. In all, we sequenced germline DNA for all the exons and intro-exon boundaries of PRSS1 and SPINK1. RESULTS: Nine (13.2%) of the 68 subjects harbored PRSS1 or SPINK1 mutations. As to PRSS1, no hereditary pancreatitis-associated variant was detected, whereas previously undescribed mutations (p.Ala148Val and c.40+1G>A) were respectively found in 2 subjects (2.9%). SPINK1 mutations were detected in 7 subjects (10.3%). Five of them exhibited known mutations (3 p.Asn34Ser, 1 p.Pro55Ser, and 1 c.88-23A>T), whereas 2 had a newly found variant (p.Arg67Gly and c.*32C>T, respectively). Only 2 familial BPH, belonging to 2 different families, were found to carry a mutation (1 with p.Ala148Val for PRSS1 and 1 with p.Asn34Ser for SPINK1). CONCLUSIONS: No known mutations of PRSS1 have been found in BPH, whereas the frequency of known SPINK1 variants is similar to that reported in the general population. No segregation of PRSS1/SPINK1 variants occurs in BPH families. Benign pancreatic hyperenzymemia cannot be explained by mutations in genes whose variants are known to be associated with pancreatitis or by mutations in other PRSS1/SPINK1 genes.

Benign pancreatic hyperenzymemia in children.

One of us recently described chronic pancreatic hyperenzymemia in the absence of pancreatic or other disease in adult subjects. The aim of the present study was to describe this form of pancreatic hyperenzymemia in children. The study involved 15 children with this condition seen from September 1996 to December 2004. After initial evaluation, each child was seen by us once annually until the end of the study. Each check-up included serum amylase (normal values 20-220 IU/L), pancreatic isoamylase (17-115 IU/L) and lipase (24-270 IU/L) determinations as well as abdominal ultrasound. In six children, fecal elastase was also determined. At the initial assessment, 13 of the 15 children had abnormal serum increases in all three enzymes, one showed an increase only in lipase, and in the remaining child all three enzymes were present in normal concentrations. These latter two children had had abnormally elevated levels of all enzymes at the examination performed before this study began. During follow-up, enzyme concentrations remained abnormally elevated, although with wide fluctuations and transient normalizations. Considering the highest values of enzymes found in the various examinations performed during this study, the increase over the upper normal limit was in the range of 1.5- to 5.2-fold for amylase, 2.2-to 8.0-fold for pancreatic isoamylase, and 2.0- to 15.4-fold for lipase. Fecal elastase was normal in the six children in whom it was measured. No child had evidence of pancreatic or other disease, either at initial evaluation or during follow-up. The results of this study describe benign pancreatic hyperenzymemia in children. Although it is a benign condition, awareness of it is important to avoid unnecessary concern and multiple diagnostic procedures.