Stefano Francesco Crinò

Azathioprine maintenance therapy to prevent relapses in autoimmune pancreatitis

Objectives:Steroids are used to induce remission in autoimmune pancreatitis (AIP). Low-dosage steroid therapy or immunosuppressant (IMs) has been proposed as maintenance therapy to prevent AIP relapse. Few and conflicting data have been published on the efficacy of azathioprine (AZA) in preventing AIP relapse. The aim of this study was to evaluate the indication and efficacy of AZA as maintenance therapy to prevent disease relapse in AIP.Methods:Patients suffering from AIP diagnosed according to the ICDC in type 1, type 2, and not otherwise specified (NOS) were divided in those treated with AZA (AZA+ group) as maintenance therapy and not treated with maintenance therapy (AZA− group). Exclusion criteria were: previous pancreatic surgery, other autoimmune diseases as indication for AZA treatment, and use of IMs different from AZA. Drug safety, clinical and instrumental outcome of AZA+ patients were evaluated.Results:A total of 23 patients (18 Males and 5 Females, mean age 54±11 years) in AZA+ group and 97 (58 Males and 39 Females, mean age 45±18 years) in AZA− group were compared. In AZA+ group, patients were significantly older (P=0.043), type 1 AIP was more frequently diagnosed (87 vs. 51%, P=0.006), sIgG4 higher (758±625 vs. 311±409 mg/dl, P<0.001), other organ involvement (OOI) more frequently observed (83 vs. 48%, P=0.002), with higher frequency of relapse before AZA treatment (78 vs. 14%, P<0.001). Three patients in AZA+ group required drug discontinuation because of adverse events. Twenty patients were therefore evaluated for outcome. Six out of 20 patients (30%) relapsed after 24±15 months (5 in pancreas and 1 on biliary tract). They were retreated with steroids and continued AZA. Two out of 6 patients (33%) had a second relapse,after respectively 11 months (in pancreas and kidney) and 22 months (in kidney).Conclusions:AZA is an effective and safe treatment to prevent AIP relapses.

Efficacy of Endoscopic Minor Papilla Sphincterotomy for Symptomatic Santorinicele

BACKGROUND & AIMS: Santorinicele, a rare focal cystic dilation of the distal portion of the dorsal pancreatic duct at the minor papilla, can be a cause of recurrent acute pancreatitis (RAP). Endoscopic minor papilla sphincterotomy (EMPS) has been evaluated as a treatment in case reports but never systematically investigated. METHODS: We performed a retrospective analysis of the efficacy of EMPS in reducing episodes of pancreatitis. We collected data on 30 patients with santorinicele and RAP who underwent EMPS from June 2009 through April 2015 at University Hospital of Verona in Italy. The mean follow‐up period was 43.8 months. RESULTS: The average number of pancreatitis episodes per year before EMPS was 1.59 vs 0.18 episodes after EMPS; the average number of pancreatitis cases that occurred during a comparable time period before EMPS was 2.63 vs 0.67 cases after EMPS (P < .0001). Complete responses to EMPS (no recurrence of pancreatitis) were reported for 80% of patients. Six patients relapsed after a mean time of 16 months. Five patients were found to have a potential cause of RAP beyond santorinicele (2 patients had post‐sphincterotomy stenosis, 1 patient was a chronic consumer of alcohol, 1 patient had a mutation in the CFTR gene, and 1 patient had a side‐branch intraductal papillary mucinous neoplasm). CONCLUSIONS: EMPS is effective in reducing the incidence of pancreatitis in patients with santorinicele.

Diagnostic yield of EUS-FNA of small (≤15 mm) solid pancreatic lesions using a 25-gauge needle

BACKGROUND Early detection of small solid pancreatic lesions is increasingly common. To date, few and contradictory data have been published about the relationship between lesion size and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) diagnostic yield. The aim of this study was to assess the relation between the size of solid pancreatic lesions and the diagnostic yield of EUS-FNA using a 25-gauge needle in a center without available rapid on-site evaluation. METHODS In the retrospective cohort study, we selected patients who underwent EUS-FNA for solid pancreatic lesions with a 25-gauge needle from October 2014 to October 2015. Patients were divided into three groups (≤15 mm, 16-25 mm and >25 mm), and the outcomes were compared. RESULTS We analyzed 163 patients. Overall adequacy, sensitivity, specificity and accuracy were 85.2%, 81.8%, 93.7%, and 80.4%, respectively. When stratified by size, the sensitivity and accuracy correlated with size (P = 0.016 and P = 0.042, respectively). Multivariate analysis showed that lesion size was the only independent factor (P = 0.019, OR = 4.76) affecting accuracy. The role of size as an independent factor affecting accuracy was confirmed in a separate multivariate analysis, where size was included in the model as a covariate (P = 0.018, OR = 1.08). CONCLUSION Our study demonstrates that, in the absence of rapid on-site evaluation, mass size affects the accuracy of EUS-FNA of solid pancreatic lesions.

Endoscopic ultrasound-through-the-needle biopsy in pancreatic cystic lesions: A multicenter study

Tissue acquisition in pancreatic cystic lesions (PCL) is the ideal method for diagnosis and risk stratification for malignancy of these lesions. Direct sampling from the walls of PCL with different devices has shown better results than cytology from cystic fluid. We carried out a retrospective, multicenter study to evaluate the feasibility, safety, and diagnostic yield of a micro‐forceps, specifically designed to be used through a 19‐gauge needle after endoscopic ultrasonography (EUS)‐guided puncture of PCL.

EUS-guided radiofrequency ablation (EUS-RFA) of solid pancreatic neoplasm using an 18-gauge needle electrode: feasibility, safety, and technical success

BACKGROUND AND AIMS Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is a promising technique for the treatment of pancreatic neoplasm. We evaluated the feasibility, safety, and technical success of pancreatic EUS-RFA performed in a single center. METHODS 9 consecutive patients (8 with pancreatic adenocarcinoma and 1 with renal cancer metastasis) were referred for EUS-RFA between November 2016 and July 2017. EUS-RFA was performed using 18-gauge internally cooled electrode with a 5 or 10 mm exposed tip. Feasibility, technical success or early and late adverse events were assessed. RESULTS One patient was excluded because of a large necrotic portion. EUS-RFA was feasible in all the other 8 (100%) cases. An ablated area inside the tumor was achieved in all treated patients. No early or late major adverse event was observed after a mean follow-up of 6 months. Three patients experienced mild post-procedural abdominal pain. CONCLUSIONS EUS-RFA seems a feasible, safe, and effective procedure for pancreatic neoplasms. Its role in the treatment and management of pancreatic masses must be further investigated.

Histologic retrieval rate of a newly designed side-bevelled 20G needle for EUS-guided tissue acquisition of solid pancreatic lesions

Background Innovative approaches to improve diagnostic yield of endoscopic ultrasound-guided tissue acquisition (EUS-TA) have focused on needle design with development of fine-needle biopsy (FNB) needles with microcore-acquisition technology. Recently, a 20-gauge (20G) antegrade-cutting-side-bevelled biopsy needle (ProCore®) was developed for EUS-TA, but data about its diagnostic performance and histological capability are scant. Objectives We assessed the diagnostic performance and histologic retrieval rate of a new 20G antegrade-cutting-side-bevelled biopsy needle compared with a 22G reverse-side-bevelled needle for EUS sampling of solid pancreatic lesions. Patients and methods A retrospective analysis of 238 consecutively collected patients who underwent EUS-TA using a 20G or a 22G ProCore® needle, without rapid on-site evaluation (ROSE), was conducted at two centres. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. Histologic tissue retrieval was evaluated applying a scoring system for each case. Results Sensitivity and specificity were estimated as 98.4–100% in the 20G-, and 94.9–100% in the 22G-needle groups, respectively (p > 0.99). The 20G procured more histologic-grade tissues (92.6% vs 49.5%, p < 0.0001) achieved by a lower number of passes (2.64 vs 3.44, p < 0.0001) compared to the 22G. Conclusions Both side-bevelled FNB needles achieved a high diagnostic sensitivity. The 20G-side-bevelled needle obtained a significantly higher microcore retrieval rate.

Palliative therapy in pancreatic cancer—interventional treatment with radiofrequency ablation/irreversible electroporation

Pancreatic cancer (PC) is a solid tumor with still a dismal prognosis. Diagnosis is usually late, when the disease is metastatic or locally advanced (LAPC). Only 20% of PC are amenable to surgery at the time of diagnosis and the vast majority of them, despite radically resected will unavoidably recur. The treatment of LAPC is a challenge. Current guidelines suggest to adopt systemic therapies upfront, based on multi-drugs chemotherapy regimens. However, the vast majority of patients will never experience conversion to surgical exploration and radical resection. Thus, there a large subgroup of LAPC patients where the only therapeutic chance is to offer palliative treatments, such as interventional ablative treatments, in order to obtain a cytoreduction of the tumor, trying to delay its growth and spread. Radiofrequency ablation (RFA) and irreversible electroporation (IRE) demonstrated to be safe and effective in obtaining a local control of the disease with some promising oncological results in terms of overall survival (OS). However, they should be adopted as a treatment strategy to adopt in parallel with other systemic therapies, within multidisciplinary choices. They are not free from complications, even serious, thus they should applied only in specialized centers of pancreatology. This review depicts the state of the art of the two techniques.

Beyond Pancreatic Cyst Epithelium: Evidence of Ovarian-Like Stroma in EUS-Guided Through-the-Needle Micro-Forceps Biopsy Specimens

mutations suggested that the role of CFTR impairment in pancreatitis could be debated [5]. For the patient, the ivacaftor treatment was initiated because of exacerbation of pancreatic manifestations. Since treatment initiation, an improvement of his lung function was observed by increase of the FEV1. However, more interestingly, all pancreatic manifestations disappeared: normalisation of the number and the aspect of stools and faecal elastase level. The patient improved in terms of pancreatic attacks, which completely disappeared after the treatment initiation. This is the first case report that suggests that the potentiator therapy may improve the pancreatic manifestations of cystic fibrosis.

Preliminary experience with pancreatic sphincterotomy as treatment for intraductal papillary mucinous neoplasm-associated recurrent pancreatitis

Background and study aims  Pancreatic intraductal papillary mucinous neoplasms (IPMN) are cystic tumors of the pancreas characterized by a malignant potential. IPMN have been associated with recurrent pancreatitis (RP). Obstruction of the main pancreatic duct by thick mucus has been postulated to be the cause of pancreatitis. In a few isolated reports, pancreatic sphincterotomy (PS) has been reported to reduce the frequency of pancreatitis. The aim of this study was to assess the efficacy of PS in patients with IPMN-associated RP. Patients and methods  We retrospectively identified patients with RP and IPMN who underwent PS from June 2010 to December 2015. Patients were included in two different groups: (a) main duct/mixed type IPMN (MD-IPMN) and (b) branch duct IPMN (BD-IPMN) with or without worrisome features/high risk stigmata. Other causes of RP were excluded. The number of pancreatitis episodes occurring during a comparable time period before and after PS was evaluated. Results  In total, 16 patients were analyzed (seven included in the MD-IPMN group and nine in the BD-IPMN group). The numbers of pancreatitis episodes occurring before and after PS were 3.5 ± 2.32 and 0.56 ± 1.03, respectively ( P  < 0.0001). Mean follow-up was 27.4 months (range 6 – 63 months). Complete, partial (reduction of pancreatitis episodes > 50 %), and no response were obtained in 11 (68.7 %), 3 (18.7 %), and 2 patients (12.5 %), respectively. One (6.25 %) case of mild post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis was observed. No cancer was detected in resected patients. None of the BD-IPMN group patients had or developed worrisome features/high risk stigmata during follow-up. Conclusions  PS seems to be effective in reducing the number of episodes of IPMN-associated pancreatitis and should be considered as a treatment option in selected clinical settings. However, active surveillance should be continued considering the malignant potential of IPMN. Further prospective controlled studies are needed to confirm our results.

Chest pain, dysphagia and hematemesis in a new mother

A 37-year-old pregnant woman underwent urgent cesarean secion at 32 weeks for eclampsia. The day of birth she presented ith a hypertensive crisis that was resolved with medical therpy. Two days later she reported acute chest pain and dysphagia ollowed by hematemesis. An urgent upper endoscopy was perormed. Immediately below the superior esophageal sphincter, a arge, purple, non-pulsatile mass tearing the mucosa and protrudng into the lumen was documented (Fig. 1 A and B). Because the esion occluded the esophageal lumen, the procedure was aborted. computed tomography (CT) scan demonstrated a 15 cm long sophageal hematoma extending to the cardia (Fig. 1C, arrows). he patient was treated conservatively. After 7 days, endoscopy erformed for another hematemesis episode revealed a large longiudinal ulcer that resulted from spontaneous endoluminal rupture f the hematoma. Endoscopic follow-up documented reepithelialzation of the ulcer surface (Fig. 1D). Esophageal hematoma consists of hemorrhagic dissection between the mucosal and muscular layer without perforation [1]. It may occur spontaneously in patients with coagulopathy or hypertension, or as a complication of thrombolytic therapy, esofageal instrumentation, variceal sclerotherapy, trauma, or foreign body ingestion. CT scan and upper endoscopy can easily differentiate this condition from other causes of chest pain, ensuring correct diagnosis. Management consists of parenteral nutrition and proton pump inhibitors until dysphagia resolution. Surgical or endoscopic intervention is rarely required.