Saurabh Mukewar

Fukuoka criteria accurately predict risk for adverse outcomes during follow-up of pancreatic cysts presumed to be intraductal papillary mucinous neoplasms

Objective Fukuoka consensus guidelines classify pancreatic cystic lesions (PCLs) presumed to be intraductal papillary mucinous neoplasms (IPMNs) into Fukuoka positive (FP) (subgroups of high-risk (HR) and worrisome features (WFs)) and Fukuoka negative (FN) (non-HR feature/WF cysts). We retrospectively estimated 5-year risk of pancreatic cancer (PC) in FN, WF and HR cysts of patients with PCL-IPMN. Design From Mayo Clinic databases, we randomly selected 2000 patients reported to have a PCL; we excluded inflammatory or suspected non-IPMN cysts and those without imaging follow-up. We re-reviewed cross-sectional imaging and abstracted clinical and follow-up data on PCL-IPMNs. The study contained 802 patients with FN cysts and 358 with FP cysts. Results Patients with PCL-IPMN had median (IQR) follow-up of 4.2 (1.8–7.1) years. Among FN cysts, 5-year PC risk was low (2–3%) regardless of cyst size (p=0.67). After excluding events in the first 6 months, 5-year PC risk remained low (0–2%) regardless of cyst size (p=0.61). Among FP cysts, HR cysts (n=66) had greater 5-year PC risk than WF cysts (n=292) (49.7% vs 4.1%; p<0.001). In HR cysts, 3-year PC risk was greatest for obstructive jaundice versus enhancing solid component or main pancreatic duct >10 mm (79.8% vs 37.3% vs 39.4%, respectively; p=0.01). Conclusions Fukuoka guidelines accurately stratify PCL-IPMNs for PC risk, with FN cysts having lowest and HR cysts having greatest risk. After 6-month follow-up, WF and FN cysts had a low 5-year PC risk. Surveillance strategies should be tailored appropriately.

Endoscopically inserted nasobiliary catheters for high dose-rate brachytherapy as part of neoadjuvant therapy for perihilar cholangiocarcinoma.

BACKGROUND AND AIM Selected patients with unresectable perihilar cholangiocarcinoma can undergo neoadjuvant chemoradiotherapy followed by liver transplantation, which has been shown to improve survival. The aim of this study was to determine the feasibility and safety of endoscopic transpapillary insertion of nasobiliary tubes (NBTs) and brachytherapy catheters for high dose-rate (HDR) brachytherapy as part of this neoadjuvant chemoradiotherapy. PATIENTS AND METHODS Medical records of patients undergoing biliary brachytherapy for hilar cholangiocarcinoma at the Mayo Clinic, Rochester were reviewed. Patients were treated with curative intent using external beam radiotherapy (4500 cGy), chemotherapy (5-FU or capecitabine), and HDR brachytherapy (930 - 1600 cGy in one to four fractions delivered over 1 - 2 days) prior to planned liver transplantation. RESULTS Between 2009 and 2013, 40 patients underwent biliary HDR brachytherapy via endoscopically placed NBTs (8.5 - 10 Fr). Patients had a median age of 55 years (range 28 - 68); 25 patients (62.5 %) had primary sclerosing cholangitis. Prior to therapy, 29 patients (72.5 %) had plastic stents, two (5 %) had metal stents, and nine (22.5 %) had no stents. Bilateral NBTs were placed in five patients (12.5 %). NBT/brachytherapy catheter displacement was seen in eight patients (20 %) - five intraprocedure and three post-procedure. A radiotherapy error and NBT kinking each occurred once. Post-procedure adverse events included: cholangitis (n = 5; 12.5 %), severe abdominal pain (n = 3; 7.5 %), duodenopathy (n = 3; 7.5 %), gastropathy (n = 3; 7.5 %), and both duodenopathy and gastropathy (n = 2; 5 %). CONCLUSION HDR biliary brachytherapy administered via endoscopically placed NBTs and brachytherapy catheters is technically feasible and appears reasonably safe in selected patients with unresectable perihilar cholangiocarcinoma.

Open-Capsule Budesonide for Refractory Celiac Disease

Objectives:Refractory celiac disease (RCD) is a rare condition often associated with poor prognosis. Various immunosuppressive medications (IMs) have been used with modest success. We describe outcomes in patients treated with open-capsule budesonide (OB), including those for whom IM treatment failed.Methods:We identified RCD patients treated with OB at Mayo Clinic, Rochester, Minnesota from 2003 to 2015. Demographic, serologic, and clinical variables were analyzed.Results:We identified 57 patients who received OB for suspected RCD. Based on clonal T-cell receptor gamma gene rearrangement or aberrant phenotype of intraepithelial lymphocytes (IELs), 13 patients (23%) were classified as having RCD-2 and 43 (75%) as RCD-1. In one patient (2%) TCR gene rearrangement status was unknown. Most patients were women (69%), mean (s.d.) age was 60.5 (3.5) years and body mass index was 28.4 (4.5) kg/m2. The majority had diarrhea (72%), with median of 6 bowel movements per day (range, 4–25). IM treatment (azathioprine, systemic corticosteroids, or regular budesonide) had failed in nearly half. Twenty-four patients (42%) had anemia and 12 (21%) had hypoalbuminemia. All had Marsh 3 lesions on biopsy: 3a (19%), 3b (46%), and 3c (35%). After OB therapy, the majority had clinical (92%) and histologic (89%) improvement. Follow-up biopsy in 7 out of 13 patients with RCD-2 (53%) showed an absence of clonal TCR gamma gene rearrangement/aberrant IEL phenotype previously seen. On follow-up, 2 patients (4%) died of enteropathy-associated T-cell lymphoma.Conclusions:Most patients with RCD show clinical and histopathologic improvement with OB therapy, including those with failure of IMs. OB is a promising therapeutic option for management of RCD.

Clinical, Biochemical, and Histopathology Features of Patients With Glycogenic Hepatopathy

Background & Aims Glycogenic hepatopathy, a syndrome characterized by hepatomegaly and increased liver transaminases in patients with type 1 diabetes, has not been well characterized in adults. We describe the clinical, biochemical, and histopathology profile of a cohort of patients with glycogenic hepatopathy. We also examined differences between patients with type 1 diabetes with versus without glycogenic hepatopathy. Methods We performed a case–control study of patients with type 1 diabetes diagnosed with glycogenic hepatopathy and patients with type 1 diabetes without glycogenic hepatopathy (control subjects). Cases were identified in the database of electronic medical records at Mayo Clinic, Rochester from January 1, 1998, through January 1, 2014. Age‐ and sex‐matched control subjects were identified from a Mayo Clinic registry of patients with type 1 diabetes who had normal levels of liver enzymes. Demographic, clinical, laboratory, and histopathology data were collected and compared between cases and control subjects. The primary outcome was difference in frequency of diabetic ketoacidosis episodes and hemoglobin (Hb) A1c levels between cases and control subjects. Results Among the 36 patients diagnosed with glycogenic hepatopathy, 20 had undergone liver biopsy analysis. Most cases were female (n = 28; 77.8%). Abdominal pain was the most common symptom (n = 23; 63.9%); 28 patients (77.8%) had hepatomegaly. All patients had poor control of diabetes (mean HbA1c level, 11.2 ± 2.4%). A higher proportion of cases had recurrent episodes of diabetic ketoacidosis (61%) than control subjects (9%) (P = .009), and cases had a higher mean level of HbA1c (11.2 ± 2.4% vs 9.0 ± 2.2% in control subjects; P = .0004). Adult cases had higher levels of aspartate transaminase (312.5 IU/L; range, 245.5–775 IU/L) than pediatric cases (157; range, 104–267 IU/L; P = .02) and lower serum levels of albumin (3.7 ± 0.5 g/dL vs 4.3 ± 0.4 g/dL for pediatric cases; P = .008). Only 16.7% of pediatric patients with glycogenic hepatopathy had growth retardation. Levels of liver transaminases were normalized at follow‐up examinations of 18 of 21 adult or pediatric patients with glycogenic hepatopathy. Conclusions More than half of patients with glycogenic hepatopathy and type 1 diabetes have recurrent episodes of diabetic ketoacidosis, and these patients have higher levels of HbA1c than patients with type 1 diabetes without glycogenic hepatopathy. We observed growth retardation in only about 17% of pediatric patients with glycogenic hepatopathy.

Risk of Pancreatic Cancer in Patients With Pancreatic Cysts and Family History of Pancreatic Cancer

Background & Aims: A diagnosis of pancreatic cancer in a first‐degree relative increases an individuals’ risk of this cancer. However, it is not clear whether this cancer risk increases in individuals with pancreatic cystic lesions who have a first‐degree relative with pancreatic cancer. The Fukuoka criteria are used to estimate risk of pancreatic cancer for patients with pancreatic cystic lesions: individuals with cysts with high risk or worrisome features (Fukuoka positive) have a higher risk of pancreatic cancer than individuals without these features (Fukuoka negative). We aimed to compare the risk of pancreatic cancer and surgery based on presence or absence of pancreatic cystic lesions and a first‐degree relative with pancreatic cancer. Methods: We performed a retrospective study of patients seen at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, through December 31, 2012. We identified individuals with: pancreatic cystic lesions and first‐degree relative with pancreatic cancer (group 1, n = 269), individuals with pancreatic cystic lesions but no first‐degree relative with pancreatic cancer (group 2, n = 1195), and individuals without pancreatic cystic lesions but with a first‐degree relative with pancreatic cancer (group 3, n = 720). We compared, among groups, as well among patients with cysts classified according to Fukuoka criteria, proportions of individuals who developed pancreatic cancer or underwent pancreatic surgery within a 5‐year period. Results: A significantly higher proportion of individuals in group 1 developed pancreatic cancer during the 5‐year period than in group 3 (6.64% vs 1.69%; P = .03); there was no significant difference between the percentage of individuals in group 1 vs group 2 who developed pancreatic cancer (6.64% vs 4.05%; P = .41). There was no significant difference in pancreatic cancer development among individuals with Fukuoka‐positive cysts with vs without a family history of pancreatic cancer (P = .39). There was no significant difference in the proportion of patients in group 1 vs group 2 who underwent pancreatic surgery for their pancreatic cyst over the 5‐year period (14.37% vs 11.80%; P = .59). Among patients with Fukuoka‐negative cysts, a significantly higher proportion underwent surgery in group 1 than in group 2 (10.90% vs 5.90%; P = .03). However, among patients with Fukuoka‐positive cysts, there was no difference in proportions of patients who underwent surgery between groups 1 and 2 (P = .66). Conclusions: In a retrospective study of patients with pancreatic cysts and/or cancer, we found that a family history of pancreatic cancer does not affect 5‐year risk of pancreatic cancer in patients with pancreatic cystic lesions. Despite this, among patients with Fukuoka‐negative cysts, a higher proportion of those with a family history of pancreatic cancer undergo surgery than patients without family history of pancreatic cancer.

The Evolution of “New Notes,” Origins, and Future Directions

The transformation of the submucosa into a working space provided a paradigm shift for endolumenal endoscopic intervention. The submucosal space can provide an undermining access to the removal of overlying mucosal disease. This space can also provide a protective mucosal barrier accommodating interventions into the deep layers of the gut wall and body cavities, such as the abdomen and mediastinum.

Epidemiologic Factors, Clinical Presentation, Causes, and Outcomes of Liver Abscess: A 35-Year Olmsted County Study

Objective To report the changing incidence, clinical presentation, microbiologic spectrum, and outcomes of pyogenic liver abscess (PLA) in Olmsted County, Minnesota, over the past 35 years. Patients and Methods The Rochester Epidemiology Project was used to identify residents with PLA from January 1, 1980, through December 31, 2014. The study included all patients older than 18 years, with the diagnosis of PLA confirmed through radiographic review and microbiologic cultures. Results In total, 72 patients received a diagnosis of PLA from 1980 through 2014. The age-adjusted incidence for men was 3.92 cases per 100,000 person-years (95% CI, 2.76-5.09 cases per 100,000 person-years) compared with 1.87 cases per 100,000 person-years (95% CI, 1.15-2.59 cases per 100,000 person-years) for women. Incidence was higher in the period from January 1, 2001, through December 31, 2014, than in the period from January 1, 1980, through December 31, 2000, for women (incidence rate ratio [IRR], 3.8; 95% CI, 1.43-10.09; P=.007) but not for men (IRR, 0.99; 95% CI, 0.55-1.76; P=.96). Fifteen additional patients had postintervention PLA (1980-2000: n=3 of 29 [10.3%] vs 2001-2015: n=12 of 58 [20.6%]). A significant association was seen between age- and sex-adjusted incidence rates of PLA and year of diagnosis (per year since 1980: IRR, 1.04; 95% CI, 1.02-1.07; P<.001) after including postintervention PLA. Streptococcus milleri was the most common organism identified (52.5%). Organisms with multidrug resistance were more common in the period from 2001 through 2014 than in the period from 1980 through 2000 (51% vs 14%; P=.005). The overall mortality rate of PLA was 16.8% (95% CI, 7.6%-25.0%) at 6 months. Conclusion The incidence of PLA is increasing, probably because of increase in frequency of hepatobiliary interventions and organisms with multidrug resistance.

Clinical Profile of Pancreatic Cystic Lesions in von Hippel-lindau Disease: A Series of 48 Patients Seen at a Tertiary Institution

Objectives Little is known about the association between pancreatic cystic lesions (PCLs) with von Hippel-Lindau disease (VHLD). In this study, we describe the clinical presentation, type of PCLs, and risk for malignancy in PCLs in VHLD. Methods Patients given a diagnosis of both VHLD and PCLs were identified from electronic medical records at Mayo Clinic, Rochester, MN, from January 1, 2000, to January 1, 2016. Various demographic, clinical, and radiologic variables were recorded. Results Forty-eight patients were identified with PCLs and VHLD. Most were female (73%), and mean (standard deviation) age was 35.9 (14.2) years. Most (92%) were asymptomatic. PCLs included simple cysts (n = 34, 69%), serous cystadenoma (n = 14, 29%), branch duct intraductal papillary neoplasm (n = 5, 10%), and cystic neuroendocrine tumors (n = 2, 4%). Eight (19%) had mixed PCLs. Cyst aspiration was performed in 8 (53%) patients who underwent EUS, and all were negative for malignancy. At a median follow-up of 84 months, no PCL-associated cancers were seen. Conclusions Simple cyst is the most common type of PCL found in VHL disease; however, other PCLs were also seen with no malignancy potential. Branch duct intraductal papillary mucinous neoplasms were present in 10%, and this association was not hitherto reported.

Recent Advances in Therapeutic Endosonography for Cancer Treatment

Therapeutic endosonography (EUS) may play an important role in the management of cancers. EUS-guided fiducial placement has a high success rate and can aid in stereotactic radiotherapy. EUS-guided tumor ablation therapies can help in palliation of locally advanced tumors. EUS-guided antitumor injection seems to be feasible and safe in animals; initial human studies suffer from small sample size and lack of controls. Randomized, controlled trials have not shown benefit over conventional therapy. EUS celiac plexus neurolysis has gained popularity and is performed by interventional endosonographers. Large trials are needed to determine the most appropriate indications and overall usefulness of these therapies.

Steroid-Responsive Chronic Pancreatitides: Autoimmune Pancreatitis and Idiopathic Duct-Centric Chronic Pancreatitis

Two different forms of steroid-responsive pancreatitides are recognized, with both being referred to as “autoimmune pancreatitis.” They differ significantly in their clinical, histological, and epidemiological features. It has recently been suggested that the term “AIP” be reserved for the disease associated with elevated serum and tissue IgG4, while the term idiopathic duct centric chronic pancreatitis (IDCP) be used for pancreas-specific form. Clinically the most frequent presentation is painless obstructive jaundice with a mass/enlargement of the pancreas at imaging, and the differential diagnosis with cancer is frequently difficult. AIP is part of a multiorgan disorder called IgG4-related disease and any organ may be involved. Therefore, more than 50 % of the patients suffering from AIP present an inflammatory involvement of other organs (particularly bile ducts, kidneys, and salivary glands). Serum IgG4 elevation is not pathognomonic of AIP and serum IgG4 should be used in combination with other features to make a diagnosis of AIP. Both AIP and IDCP respond to steroids. In relapses of AIP the use of immunosuppressive drugs or of biologic agents may be considered.