Mario Pelaez-Luna

Value of serum IgG4 in the diagnosis of autoimmune pancreatitis and in distinguishing it from pancreatic cancer.

OBJECTIVES:To determine the sensitivity and specificity of elevated serum IgG4 level for the diagnosis of autoimmune pancreatitis (AIP) and its ability to distinguish AIP from pancreatic cancer, its main differential diagnosis.METHODS:We measured serum IgG4 levels (normal 8–140 mg/dL) in 510 patients including 45 with AIP, 135 with pancreatic cancer, 62 with no pancreatic disease, and 268 with other pancreatic diseases.RESULTS:Sensitivity, specificity, and positive predictive values for elevated serum IgG4 (>140 mg/dL) for diagnosis of AIP were 76%, 93%, and 36%, respectively, and 53%, 99%, and 75%, respectively, for IgG4 of >280 mg/dL. Among subjects with elevated IgG4, non-AIP subjects (N = 32) differed from AIP subjects (N = 34) in that they were more likely to be female (45% vs 9%, P < 0.001), less likely to have serum IgG4 >280 mg/dL (13% vs 71%, P < 0.001), or elevation of total IgG (16% vs 56%, P < 0.001). Serum IgG4 levels were elevated in 13/135 (10%) pancreatic cancer patients; however, only 1% had IgG4 levels >280 mg/dL compared with 53% of AIP. Compared with AIP, pancreatic cancer patients were more likely to have CA19-9 levels of >100 U/mL (71% vs 9%, P < 0.001).CONCLUSION:Elevated serum IgG4 levels are characteristic of AIP. However, mild (<2-fold) elevations in serum IgG4 are seen in up to 10% of subjects without AIP including pancreatic cancer and cannot be used alone to distinguish AIP from pancreatic cancer. Because AIP is uncommon, IgG4 elevations in patients with low pretest probability of having AIP are likely to represent false positives.

Do consensus indications for resection in branch duct intraductal papillary mucinous neoplasm predict malignancy? A study of 147 patients

BACKGROUND AND AIMS:Recent consensus guidelines suggest that presence of ≥1 of the following is an indication for resection (IR) of branch duct intraductal papillary mucinous neoplasm (IPMN-Br): cyst-related symptoms, main pancreatic duct diameter ≥10 mm, cyst size ≥30 mm, intramural nodules, or cyst fluid cytology suspicious/positive for malignancy. Among a cohort of patients with IPMN-Br we determined if the consensus IR (CIR), presence of multifocal IPMN-Br, or growth of cyst size on follow-up predict malignancy.METHODS:We identified 147 patients with IPMN-Br of whom 66 underwent surgical resection at diagnosis and 81 were followed conservatively, of whom 11 were resected during follow-up. Clinical, imaging, histological, and cyst fluid characteristics from all 147 patients with IPMN-Br were obtained from clinical records and/or by contacting the patients. In all cases, presence of CIR at baseline and during follow-up (N = 66), presence of multifocal cysts (N = 57), and increase in cyst size (N = 38) were noted.RESULTS:Among the 77 resected IPMN-Brs, at initial evaluation 61 had at least one CIR and 16 had none. Malignancy was present in 9/61 (15%) with CIR and 0/16 without IR (P = 0.1). When presence of any one of the CIR was taken as an indicator of malignancy, the CIR had a sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 23%, 14%, and 100%, respectively. Prevalence of malignancy in those with single versus multifocal IPMN-Br was similar (13% vs 11%). No patient has developed malignancy after a median follow-up of 15 months. So far, none of the 38 patients with increase in cyst size on follow-up has developed malignancy related symptoms.CONCLUSIONS:Suggested consensus indications for resection identify all patients with malignancy; however, their specificity is low. In the short term it would be safe to follow patients without these features.

Obesity : A risk factor for severe acute biliary and alcoholic pancreatitis

Objective: In this study we evaluate the association between obesity and complication development in patients with a first-attack acute pancreatitis (AP), and investigate the influence of comorbid factors on this association. Methods: Medical records of 150 patients with AP were reviewed. General data, AP etiology, admission AP prognostic criteria, and occurrence of complications were recorded. Patients were classified according to body mass index (BMI) as obese (BMI > 25 kg/m2) and nonobese (BMI ≤ 25 kg/m2). Results: Prevalence of obesity was 57%. Thirty-eight percent of the obese patients developed complications as compared with 21% of the nonobese (RR = 1.74; 95% CI, 1–2.9). The risk for severe AP increased according to the degree of obesity. Pancreatic and peripancreatic necrosis was more common in obese patients (17.6% vs 6%), as was the incidence of infectious complications. The risk for severe AP was highest in obese patients with either alcoholic (RR = 5.3; 95% CI, 1.2–23) or biliary etiology (RR = 5.2, 95% CI, 1–26). Conclusion: Obesity may predispose to a complicated course of AP, especially if it is secondary to alcohol or gallstones. Further studies are needed to establish the precise prognostic value of obesity in AP, as well as the pathogenic mechanisms involved in the process.

Disconnected pancreatic duct syndrome in severe acute pancreatitis: clinical and imaging characteristics and outcomes in a cohort of 31 cases

BACKGROUND Information regarding the natural history, clinical characteristics, and outcomes of disconnected pancreatic duct syndrome (DPDS) is limited. OBJECTIVE To describe clinical characteristics and outcomes of DPDS. DESIGN A retrospective review of the Mayo Clinic endoscopy and hospital service database. SETTING Tertiary-referral center. PATIENTS We identified 31 DPDS cases from 1999 to 2006. INTERVENTIONS Endoscopic drainage of pancreatic-fluid collections. MAIN OUTCOME MEASUREMENTS The relationship between demographic and clinical data with endoscopic treatment and clinical outcomes in DPDS cases. RESULTS The median patient age was 53 years (range 20-83 years); 48% were men. The most common etiology of acute pancreatitis (AP) was biliary (55%) followed by idiopathic (27%). The median interval between the diagnoses of AP and DPDS was 56 days (range 3-251 days); the median follow-up after the last ERCP or surgical procedure was 7 months (range 0-90 months). The DPDS location included the following: pancreas head 6%, neck 58%, body 26%, and tail 10%. Twenty-six patients had initial endoscopic treatment (19 had long-term improvement; 7 failed treatment and required surgery) and 5 underwent immediate surgery. Mortality was 0%; 26% developed chronic pancreatitis (CP) and 16% diabetes mellitus (DM); 10% resolved completely, 45% had smaller fluid collections, and 26% patients were lost to follow-up. No relationship between demographic and clinical data with endoscopic and clinical outcomes was found. CONCLUSIONS Endoscopic treatment temporarily improved DPDS, with a failure rate of 23%. Immediate surgery was not required in all cases. CP and/or pancreatic atrophy occurred relatively shortly after the DPDS diagnosis in 26% and DM in 16% of cases. DPDS did not lead to mortality. Early surgery may be considered after initially stabilizing the fluid collection with endoscopic therapy.

Resectability of presymptomatic pancreatic cancer and its relationship to onset of diabetes: a retrospective review of CT scans and fasting glucose values prior to diagnosis.

BACKGROUND:The timeline of progression of pancreatic cancer from resectable to unresectable disease is unknown. New-onset diabetes often occurs in pancreatic cancer. It is unclear if the cancer is resectable at the onset of diabetes. We (a) determined the resectability of pancreatic cancer on abdominal CT scans done prior to clinical diagnosis and (b) correlated resectability with onset of diabetes.METHODS:All CT scans done at diagnosis or before pancreatic cancer diagnosis were reviewed and pancreatic changes classified as normal, potentially resectable, or unresectable pancreatic cancer. Fasting blood glucose values obtained at and prior to diagnosis were available in 18 patients. The date of onset of diabetes and the interval between onset of diabetes and diagnosis of cancer were noted.RESULTS:Thirty patients fulfilled inclusion criteria. Prior to diagnosis, 28 patients had 38 CT scans done at a median of 18 months (range 1–41) before cancer diagnosis. At cancer diagnosis, only 7/30 patients could undergo margin-negative surgical resection. CT scans done ≥6 months prior to diagnosis showed either a normal pancreas (N = 20) or a resectable mass (N = 6); none had unresectable cancer. The mean interval between onset of diabetes and diagnosis of pancreatic cancer was 10 months (range 5–29 months). At the onset of diabetes, 3 patients had normal pancreas, 6 had resectable, and 4 had unresectable pancreatic cancer.CONCLUSIONS:Pancreatic cancer is frequently undetectable or resectable on CT scans done ≥6 months prior to clinical diagnosis. At onset of diabetes, pancreatic cancers are generally resectable.

PRSS1 and SPINK1 mutations in idiopathic chronic and recurrent acute pancreatitis

AIM To identify gene mutations in PRSS1 and SPINK1 in individuals with early onset idiopathic chronic or recurrent acute pancreatitis. METHODS The cationic trypsinogen gene (PRSS1; exons 2 and 3) and the serine protease inhibitor Kazal 1 gene (SPINK1; exon 3) were selectively amplified and sequenced from blood samples of 19 patients admitted to the Pancreas Clinic at our institution with chronic pancreatitis and/or idiopathic recurrent acute pancreatitis that were diagnosed or with onset before age 35. Fifty healthy volunteers served as controls. Whole blood samples were collected and gene specific sequences were amplified by polymerase chain reaction (PCR). All PCR products were subsequently sequenced in order to identify the presence of any mutations. RESULTS Nineteen patients with pancreatitis (14 males; median age 24 years, range 15-48 years) were included in this study, of which five showed the presence of gene mutations. Direct sequencing results indicated the presence of two previously unidentified mutations in exon 2 of PRSS1 (V39E and N42S) in two patients with recurrent acute pancreatitis. Two cases had the N34S SPINK1 mutation. Analysis of the relatives of one patient homozygous for this mutation showed that five of the six family members carried the N34S SPINK1 mutation. Of these members, three were healthy heterozygous carriers and two were homozygotes (one sibling had diabetes, the other was healthy). Another patient was heterozygous for a novel SPINK1 mutation located on exon 3 (V46D). All members from this patients family had normal genotypes, indicating that it was a de novo mutation. No mutations in either gene were present in the control subjects. CONCLUSION Two novel PRSS1 mutations and one novel SPINK1 mutation were identified in Mexican patients with early onset idiopathic recurrent acute pancreatitis.

Branch Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas in Solid Organ Transplant Recipients

OBJECTIVES:In immunosuppressed patients with branch duct intraductal papillary mucinous neoplasm (IPMN-Br) associated with solid organ transplantation, the risk of major pancreatic surgery has to be weighed against the risk of progression to malignancy. Recent studies show that IPMN-Br without consensus indications for resection (CIR) can be followed conservatively. We analyzed the course of IPMN-Br in patients with and without solid organ transplant.METHODS:We compared clinical and imaging data at diagnosis and follow-up of 33 IPMN-Br patients with solid organ transplant (T-IPMN-Br) with those of 57 IPMN-Br patients who did not undergo transplantation (NT-IPMN-Br). In T-IPMN-Br, we noted pre- and post-transplant imaging and cyst characteristics. This case–control study was conducted in a tertiary-care hospital for patients with IPMN-Br.RESULTS:T-IPMN-Br patients were younger than the NT-IPMN-Br patients (63 vs. 68 years, P=0.01). The median duration of follow-up for the groups was similar (29 vs. 28 months, P<NS). CIR were present in 24% (8/33) of T-IPMN-Br patients and 32% (18/57) of NT-IPMN-Br. New CIR were noted in 6% (2/33) of patients in the T-IPMN-Br group during a median follow-up of 17 months (range, 3–100 months) compared with 4% (2/57) of patients in the NT-IPMN-Br group (P=NS). Eleven patients (10 NT-IPMN-Br, 1 T-IPMN-Br) underwent surgery during follow-up. Only one NT-IPMN-Br patient was diagnosed with malignancy; all others had benign IPMN-Br.CONCLUSIONS:In participants with IPMN-Br, short-term follow-up after solid organ transplant was not associated with any significant change in cyst characteristics suggesting that incidental IPMN-Br, even in the setting of immunosuppression post-transplant, can be followed conservatively.

Percutaneous Endoscopic Gastrostomy Complication Rates and Compliance With the American Society for Gastrointestinal Endoscopy Guidelines for the Management of Antithrombotic Therapy

BACKGROUND The American Society for Gastrointestinal Endoscopy (ASGE) has published recommendations in regards to anticoagulant (AC) and antiplatelet (AP) therapy management during endoscopic procedures. So far, no study has assessed either ASGE recommendation compliance during percutaneous endoscopic gastrostomy (PEG) placement or procedure-associated complication rates as related to the observance of these recommendations. The aims of this study were to compare the incidence and type of complications during PEG placement in patients receiving or not receiving AC and/or AP therapy and to determine the compliance with ASGEs AC and AP management guidelines. METHODS Medical files of patients who underwent PEG placement from January 2004 to December 2008 were reviewed. Clinical and procedure-related data were recorded. Patients were separated into 1 of 2 groups: patients under AP and/or AC therapy prior to PEG placement (n = 51) and a control group of patients (n = 40) not receiving any AP and/or AC treatment at least 6 months prior to the procedure. RESULTS A total of 91 patients (51 cases) were included. Groups were comparable in demographics and clinical characteristics. No differences in the frequency and type of complications were found between groups. ASGEs recommendations were not followed in any of these patients. CONCLUSIONS Overall PEG placement complication rate was 13.7%. AP therapy may be safely discontinued closer to the time of endoscopic procedure than the time currently recommended by the ASGE guidelines.

Mirizzi syndrome presenting as painless jaundice: a rare entity diagnosed by EUS

A 55-year-old woman presented with a 3-week history of flu-like symptoms, 15-pound weight loss, steatorrhea, and painless jaundice. Laboratory investigations showed elevated total bilirubin, direct bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase levels. An abdominal CTscan showed intrahepatic biliary ductal dilatation with a faintly calcified area in the common bile duct (CBD) region (A). EUS was performed because an underlying malignancy was suspected. Initial examination with a duodenoscope showed hemobilia, with purulent material extruding from an otherwise normal-appearing major papilla (B). A linear echoendoscope showed a hypoechoic multilaminated structure with internal calcification at the

M1269 Lack of Aggressive Early Fluid Resuscitation Is Associated with Organ Failure in Acute Pancreatitis

pancreatitis, we investigated the expression of HO-1 in patients with pancreatitis as compared to patients with non-pancreatic disease and healthy volunteers. Methods: 18 patients (4 with non pancreatic disease and 14 with pancreatitis) and 8 normal healthy controls of similar age and gender were recruited. Blood was drawn early during admission (day1) and 48 h later (day3). Peripheral blood mononuclear cells (PBMC) were isolated and HO-1 levels were assessed by flow cytometry (FACS) and western blotting (WB). HO-1 mean fluorescence intensity (MFI) was normalized to standardized beads to allow for FACS comparison between samples processed at different days. Isolated PBMCs were cultured for 24 and 48 h in the absence or presence of hemin to assess inducibility of HO-1. Results: MFI corresponding to HO-1 expression was highest in circulating neutrophils and monocytes as determined by FACS. Patients with acute pancreatitis had the highest levels of HO-1 expression at day1 (7709+/-1193; arbitrary units) as compared to patients with non-pancreatitis (3795+/-1305; p<0.05) and healthy controls (3758+/-613; p=0.01). Furthermore, day3 HO-1 levels in patients with acute pancreatitis decreased with clinical improvement, whereas samples from non-pancreatitis patients and healthy volunteers either increased slightly or remained unchanged. Culturing of PBMC isolated from patients with acute pancreatitis, followed by induction with hemin, leads to a marked further up-regulation of HO-1. In contrast, PBMC from healthy volunteers are less responsive to hemin-mediated HO-1 induction. Conclusions: (i) pancreatitis leads to reversible up-regulation of HO-1 in PBMC during the acute phase that correlates with clinical improvement, and involves primarily monocytes and neutrophils; (ii) PBMC from acutely ill patients with pancreatitis appear to be primed to HO-1 induction by hemin, which implies that administration of heminmay offer a beneficial therapeutic effect.