The Role of Endoscopic Ultrasound and Ancillary Techniques in the Diagnosis of Autoimmune Pancreatitis: A Comprehensive Review.

Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis with a multifactorial pathogenesis. Historically, it has been classified as type 1 and type 2, according to its clinical and histological features. The diagnosis of AIP is challenging and relies on a combination of clinical, histopathologic, serologic, and imaging characteristics. In the available guidelines, the imaging hallmarks of AIP are based on cross-sectional imaging and cholangiopancreatography retrograde endoscopic findings. Endoscopic ultrasound (EUS) is generally used for pancreatic tissue acquisition to rule out pancreatic cancer and diagnose AIP with limited accuracy. Several papers reported the reliability of EUS for providing informative morphologic features of AIP. Nowadays, the improvement in the resolution of EUS conventional images and the development of new ancillary technologies have further increased the diagnostic yield of EUS: contrast-enhanced EUS and EUS elastography are non-invasive and real-time techniques that strongly support the diagnosis and management of pancreatic diseases. In this review article, we will present the role of conventional EUS and ancillary diagnostic techniques in the diagnosis of AIP to support clinicians and endosonographers in managing this condition.

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.

Preoperative carbohydrate loading before elective abdominal surgery: A systematic review and network meta-analysis of phase II/III randomized controlled trials.

BACKGROUND & AIMS: The preoperative use of carbohydrate loading (CHO) is recommended in patients undergoing abdominal surgery, even if the advantages remain debatable. The aim was to evaluate the CHO benefits in patients undergoing abdominal surgery. METHODS: A systematic search of randomized clinical trials was made. A frequentist random-effects network meta-analysis was carried out, reporting the surface under the cumulative ranking (SUCRA). The primary endpoint regarded the morbidity rate. The secondary endpoints were aspiration/regurgitation rates, the length of stay (LOS), the rate of postoperative nausea and vomiting (PONV), the changes (Δ) in insulin sensitivity or resistance, and the postoperative C- reactive protein (CRP) values. RESULTS: CHO loading and water administration had a similar probability of being the approach with a lower morbidity rate (SUCRA = 62.4% and 64.7%). CHO and clear water also had a similar chance of avoiding the PONV (SUCRA of 80.8% and 77%). The aspiration regurgitation rate was not relevant in non-fasting patients (0.06%). CHO administration was associated with the shorter hospitalization (SUCRA 86.9%), with the best metabolic profile (SUCRA values for insulin resistance and sensitivity were 81.1% and 76%). CHO enriched was the best approach for postoperative CRP values. Preoperative fasting was the worst approach for morbidity, PONV, insulin resistance and sensitivity, and CRP (SUCRA values of 32.1%, 21.7%, 10.2%, 3.2%, and 2.0%). CONCLUSION: Both preoperative CHO loading and clear water use were superior to the fasting about morbidity. CHO drinks use could provide specific advantages, reduce the PONV rate, and improve carbohydrate homeostasis, inflammatory pathway, and hospitalization.

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.

Performance of EUS-FNB in solid pancreatic masses: a lesson from 463 consecutive procedures and a practical nomogram.

The study's main goal was the diagnostic adequacy of pancreatic endoscopic ultrasonographic (EUS) fine-needle biopsy (FNB) and associated predictive factors. The secondary objective was to define the diagnostic accuracy of EUS-FNB in the diagnosis of pancreatic masses and pancreatic malignancies. None of the studies reported the diagnostic adequacy and accuracy of EUS. We retrospectively identified patients with solid pancreatic lesions that underwent EUS-FNB between 2013, and 2018. We calculated diagnostic adequacy and related factors. Using definitive histology on the surgically resected specimen as the gold standard, we calculated diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNB. We identified a total of 463 procedures. Diagnostic specimens were adequate in 436 procedures (94.1%), while 27 biopsies provided insufficient samples (5.9%). The multivariate analysis showed that lesion size and needle caliper were the only factors influencing diagnostic adequacy. The use of a biopsy needle (OR 0.69, 95% CI 0.30-0.1.63, P 0.400) did not improve sample adequacy. We calculated sensitivity (100%), specificity (93.2%), diagnostic accuracy (93.2%), positive predictive value (97.1%), and negative predictive value (100%) using resected specimen as the gold standard. We found no significant complications. EUS-FNB is a reliable technique for the histological characterization of solid pancreatic masses.

CEing More-Assessing Small Bowel Crohn's with Capsule Endoscopy (CE).

INTRODUCTION: Small bowel involvement is very common in Crohn's disease. Ileocolonoscopy, cross-sectional imaging modalities, and video capsule endoscopy are the tools currently used to investigate such involvement. AREAS COVERED: Herein we report the case of a 47-year-old man with a history of ileocolic Crohn's disease and persistent, unexplained iron deficiency anemia. EXPERT COMMENTARY: Capsule endoscopy, by accurately identifying small intestinal mucosal lesions, can improve outcomes.

Blumgart Anastomosis After Pancreaticoduodenectomy. A Comprehensive Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: The superiority of Blumgart anastomosis (BA) over non-BA duct to mucosa (non-BA DtoM) still remains under debate. METHODS: We performed a systematic search of studies comparing BA to non-BA DtoM. The primary endpoint was CR-POPF. Postoperative morbidity and mortality, post-pancreatectomy hemorrhage (PPH), delayed gastric emptying (DGE), reoperation rate, and length of stay (LOS) were evaluated as secondary endpoints. The meta-analysis was carried out using random effect. The results were reported as odds ratio (OR), risk difference (RD), weighted mean difference (WMD), and number needed to treat (NNT). RESULTS: Twelve papers involving 2368 patients: 1075 BA and 1193 non-BA DtoM were included. Regarding the primary endpoint, BA was superior to non-BA DtoM (RD = 0.10; 95% CI: -0.16 to -0.04; NNT = 9). The multivariate ORs' meta-analysis confirmed BA's protective role (OR 0.26; 95% CI: 0.09 to 0.79). BA was superior to DtoM regarding overall morbidity (RD = -0.10; 95% CI: -0.18 to -0.02; NNT = 25), PPH (RD = -0.03; 95% CI -0.06 to -0.01; NNT = 33), and LOS (- 4.2 days; -7.1 to -1.2 95% CI). CONCLUSION: BA seems to be superior to non-BA DtoM in avoiding CR-POPF.

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 of Advanced Gastro-Entero-Pancreatic Neuro-Endocrine Tumors: A Systematic Review and Network Meta-Analysis of Phase III Randomized Controlled Trials.

Several new therapies have been approved to treat advanced gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) in the last twenty years. In this systematic review and meta-analysis, we searched MEDLINE, ISI Web of Science, and Scopus phase III randomized controlled trials (RCTs) comparing two or more therapies for unresectable GEP-NENs. Network metanalysis was used to overcome the multiarm problem. For each arm, we described the surface under the cumulative ranking (SUCRA) curves. The primary endpoints were progression-free survival and grade 3-4 of toxicity. We included nine studies involving a total of 2362 patients and 5 intervention arms: SSA alone, two IFN-α plus SSA, two Everolimus alone, one Everolimus plus SSA, one Sunitinib alone, one 177Lu-Dotatate plus SSA, and one Bevacizumab plus SSA. 177Lu-Dotatate plus SSA had the highest probability (99.6%) of being associated with the longest PFS. This approach was followed by Sunitinib use (64.5%), IFN-α plus SSA one (53.0%), SSA alone (46.6%), Bevacizumab plus SSA one (45.0%), and Everolimus ± SSA one (33.6%). The placebo administration had the lowest probability of being associated with the longest PFS (7.6%). Placebo or Bevacizumab use had the highest probability of being the safest (73.7% and 76.7%), followed by SSA alone (65.0%), IFN-α plus SSA (52.4%), 177Lu-Dotatate plus SSA (49.4%), and Sunitinib alone (28.8%). The Everolimus-based approach had the lowest probability of being the safest (3.9%). The best approaches were SSA alone or combined with 177Lu-Dotatate.

Another Use for EUS: Removal of a Transesophageal-Migrated Mediastinal Foreign Body.

Removal of foreign bodies from the upper gastrointestinal tract, though a common occurrence, can be technically challenging and risky. We report the case of a young man that, after eating a pizza cooked in a wood-burning oven, reported a sense of foreign body. Though the first evaluation by fiberoptic laryngoscopy found no foreign body, after a few weeks, the patient was readmitted from the ER for worsening symptoms and fever. A CT scan showed a metallic mediastinal foreign body inside a large fluid collection. After multidisciplinary evaluation, an endoscopic removal was attempted by accessing the mediastinal collection through EUS-guided positioning of a Hot Axios™ stent. The cavity was drained by naso-esophageal suction. The foreign body was a fragment of the brush used to clean the oven. The patient is now doing well after 7 months.

Granular Data: A Rare Submucosal Tumor of the Colon-Case Report and Review of the Literature.

INTRODUCTION: Granular cellular tumors are unusual lesions that can occur in the gastrointestinal tract, where they localize most commonly to the esophagus followed by the colon. AREAS COVERED: We report a case of a young man with a sub-epithelial lesion of the ascending colon, removed by endoscopic submucosal dissection. Histological examination revealed a granular cellular tumor without features of malignancy. We present a systematic review of the English literature evaluating granular cellular tumors of lower gastrointestinal tract. EXPERT COMMENTARY: These tumors are usually asymptomatic and discovered incidentally during endoscopy performed for other reasons. Though their histological behavior is usually benign, 1-2% are malignant. Therefore, it is important that these lesions are excised and adequately pathologically characterized.

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.

The use of comprehensive complication Index® in pancreatic surgery: a comparison with the Clavien-Dindo system in a high volume center.

BACKGROUND: The Clavien-Dindo classification (CDC) system and Comprehensive Complication Index (CCI®) are both widely used methods for reporting the burden of postoperative complications. This study aimed to compare the accuracy of the CDC and CCI® in predicting outcomes associated with pancreatic surgery. METHODS: The CCI® and CDC were applied to 668 patients who underwent pancreatic resection. Length of postoperative stay (LOS) was chosen as the primary outcome variable. The comparison between CCI® and CDC was made with the Spearman test, reporting þs with standard error (SE) and logistic regression, reporting the Odds Ratio (OR) and Area Under the Curve with SE. RESULTS: The median value with the interquartile range (IQR) of CCI® was 20.9 (0-29.6). Both CCI® (þs = 0.609) and CDC (0.590) were significantly (P < 0.001) correlated to LOS. CCI (OR 1.056 and OR 1.052) and CDC (OR 1.978, and OR 1.994) predicted (P < 0.001) LOS over the median and 75th percentile. The accuracy of CCI® was superior to CDC for LOS over 50th (0.785 vs. 0.740; P = 0.004) and over 75th (0.835 vs. 0.761; P < 0.001) percentile. CONCLUSION: The accuracy of CCI® in measuring the complicated postoperative course was superior to CDC, correctly classifying eight patients every ten tested.

Endoscopic Ultrasound-Guided Stented Gastro-Gastrostomy for Strictured Vertical Banded Gastroplasty.

Herein, we make a video presentation of an endoscopic reversal of a strictured vertical banded gastroplasty (VBG), carried out through an endoscopic ultrasonography (EUS)-guided transluminal therapy system, in order to accurately identify the common gastric wall and to allow the application of an endoscopic stent. The operative time was 60 min, and no intraoperative complication was recorded. On postoperative day 1, an upper GI swallow showed the oral contrast easily flowing into the body of the stomach throughout the stent. A semi-solid diet was started on day 1. The postoperative course was uneventful, and the patient was discharged on day 2. At the 3-month follow-up visit, the patient denied further symptoms. The follow-up upper GI swallow and endoscopy showed a patent gastro-gastrostomy and no residual gastric pouch dilation or stagnation of the oral contrast, and the stent was therefore removed. Gastro-gastrostomy by endoscopic stenting appears to be an effective option to relief symptoms in strictured VBG, and EUS guidance has made access to the target structure easier and safer.

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.

Incidental diagnosis of very small rectal neuroendocrine neoplasms: when should endoscopic submucosal dissection be performed? A single ENETS centre experience.

PURPOSE: The management of small (≤5 mm) rectal neuroendocrine neoplasms (r-NENs), incidentally removed during colonoscopy, still remains under debate. METHODS: All consecutive patients affected by r-NENs from January 2013 to December 2017 were studied. The inclusion criteria were: (1) patients having an incidental pathological diagnosis of very small (≤5 mm) polypoid r-NENs; (2) patients treated with a standard polypectomy as first-line therapy and (3) patients treated by endoscopic submucosal dissection (ESD) as salvage therapy. The primary endpoint was to identify the factors related to residual disease after a standard polypectomy. The secondary endpoint was to calculate the accuracy of endoscopic ultrasound (EUS), grading and size in predicting residual disease. RESULTS: Starting from a prospective database of 123 consecutive patients affected by r-NENs, only 31 met the inclusion criteria. A final pathological examination of an ESD specimen showed residual disease in 7 out of 31 patients (22.6%). A multivariate analysis showed that the size of the polyps was the only independent factor related to residual disease with an odds ratio of 8.7 ± 7.5 (P = 0.013) for each millimetre. The accuracy of EUS, grading and tumour size (3.1 mm cut-off point) and area under the curves were 0.661 ± 0.111, 0.631 ± 0.109 and 0.821 ± 0.109, respectively. CONCLUSIONS: When the r-NEN polyp was larger than 3 mm, ESD was indicated. Unlike the size of the tumour, grading and EUS features did not accurately predict residual disease.

A cure model survival analysis of patients affected by small intestinal neuroendocrine neoplasms: the Bologna ENETS center experience.

PURPOSE: The primary end-point was to evaluate the cure fraction. Secondary end-points were to investigate the time to cure, the excess of death risk, the probability of cure and the factors related to these parameters. METHODS: Retrospective study of an ENETS database regarding patients affected by Si-NENs. For each patients, clinical, pathological and follow-up data were collected. The survival analysis was made using a novel approach: the cure model approach. RESULTS: The cure fraction was 92.1%. The death risk, time to cure and the probability of cure were 6/1000 person-years, 3.6 years and 98.2%, respectively. The independent factors influencing these parameters were the grading and the R status (P = 0.041 and P = 0.017, respectively). Patients affected by Si-NENs G2 increased the death risk and time to cure respect to Si-NENs G1 (51 versus 6 per 1000 person-years and 5.1 versus 3.6 years, respectively) as well as patients not operated respect to those radically resected (R0/1) (66 versus 1 per 1000 person-years and 4.8 versus 0.4 years, respectively). The probability of cure decreased (88.1 versus 97.8% and 80.4 versus 99.7%, respectively). R2 resection shows better results than no resection. CONCLUSIONS: A large portion of patients affected by Si-NENs can be cured. The highest probability of cure regards patients with Si-NENs G1 who underwent to R0/R1 resection; the lower, those with Si-NENs G2 and no resection. R2 resection seems to be preferred respect to no resection.

Enteroscopy in children.

INTRODUCTION: Device-assisted enteroscopy is a new endoscopic technique for the evaluation of small bowel in adults and children. Data in pediatric population are limited. This review aims to identify diagnostic and therapeutic benefits of enteroscopy in children. METHODS: We have analysed paediatric literature on device-assisted enteroscopy focusing on indications, technical aspects and complications, with attention given to adult publications that may be applicable to the paediatric population. RESULTS: Obscure gastrointestinal bleeding, Crohn's disease and small bowel polyps are the main indications of enteroscopy in children. Device-assisted enteroscopy has high diagnostic yield for the main paediatric indications, but MR-enterography and capsule endoscopy should be used beforehand in diagnostic work-up to better identify candidates for enteroscopy and to improve its diagnostic and therapeutic yield. Major complications are rare and mostly related to therapeutic procedures. CONCLUSION: Despite limited data in the paediatric population, device-assisted enteroscopy represents a useful and safe endoscopic technique in children. Its use, combined with MR-enterography and capsule endoscopy, allows identification and treatment of many of the small bowel paediatric diseases with a low risk of complications.