Management of Patients With Pancreatic Cysts: Analysis of Possible False-Negative Cases of Malignancy.

GOALS: To examine the utility of integrated molecular pathology (IMP) in managing surveillance of pancreatic cysts based on outcomes and analysis of false negatives (FNs) from a previously published cohort (n=492). BACKGROUND: In endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of cyst fluid lacking malignant cytology, IMP demonstrated better risk stratification for malignancy at approximately 3 years' follow-up than International Consensus Guideline (Fukuoka) 2012 management recommendations in such cases. STUDY: Patient outcomes and clinical features of Fukuoka and IMP FN cases were reviewed. Practical guidance for appropriate surveillance intervals and surgery decisions using IMP were derived from follow-up data, considering EUS-FNA sampling limitations and high-risk clinical circumstances observed. Surveillance intervals for patients based on IMP predictive value were compared with those of Fukuoka. RESULTS: Outcomes at follow-up for IMP low-risk diagnoses supported surveillance every 2 to 3 years, independent of cyst size, when EUS-FNA sampling limitations or high-risk clinical circumstances were absent. In 10 of 11 patients with FN IMP diagnoses (2% of cohort), EUS-FNA sampling limitations existed; Fukuoka identified high risk in 9 of 11 cases. In 4 of 6 FN cases by Fukuoka (1% of cohort), IMP identified high risk. Overall, 55% of cases had possible sampling limitations and 37% had high-risk clinical circumstances. Outcomes support more cautious management in such cases when using IMP. CONCLUSIONS: Adjunct use of IMP can provide evidence for relaxed surveillance of patients with benign cysts that meet Fukuoka criteria for closer observation or surgery. Although infrequent, FN results with IMP can be associated with EUS-FNA sampling limitations or high-risk clinical circumstances.

Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts.

BACKGROUND AND STUDY AIMS: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts. PATIENTS AND METHODS: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis ("benign"/"statistically indolent" vs. "statistically higher risk [SHR]"/ "aggressive") or an International Consensus Guideline (Sendai 2012) criteria model for "surveillance" vs. "surgery." The Cox proportional hazards model determined hazard ratios for malignancy. RESULTS: Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (P < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P < 0.0001). CONCLUSION: IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria.

Endoscopic Ultrasound-Guided Self-Expandable Metal Stent Placement for the Treatment of Infected Pancreatic Pseudocysts.

The standard endoscopic ultrasound (EUS) approach of cystogastrostomy involves the use of series of plastic pigtail stents that are placed through the wall of the cyst. The use of a single stent has also been described in the literature. Here we describe five cases of EUS-guided cystogastrostomy with irrigation of infected pancreatic pseudocysts using a single self-expandable metal stent (SEMS). To our knowledge this has not been described in the literature in the United States. This novice approach will have significant implications in the management of infected pseudocysts with a lower morbidity, mortality and overall cost compared to conventional management such as surgery or percutaneous drainage.

Safety and efficacy of endoscopic spray cryotherapy for Barrett's esophagus with high-grade dysplasia.

BACKGROUND: Endoscopic ablation to treat Barrett's esophagus (BE) with high-grade dysplasia (HGD) is associated with a decreased incidence of esophageal adenocarcinoma. Endoscopic spray cryotherapy (CRYO) demonstrates promising preliminary data. OBJECTIVE: To assess the safety and efficacy of CRYO in BE with HGD. DESIGN: Multicenter, retrospective cohort study. SETTING: Nine academic and community centers; treatment period, 2007 to 2009. PATIENTS: Subjects with HGD confirmed by 2 pathologists. Previous EMR was allowed if residual HGD remained. INTERVENTIONS: CRYO with follow-up biopsies. MAIN OUTCOME MEASUREMENTS: Complete eradication of HGD with persistent low-grade dysplasia, complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and complete eradication of all intestinal metaplasia. RESULTS: Ninety-eight subjects (mean age 65.4 years, 83% male) with BE and HGD (mean length 5.3 cm) underwent 333 treatments (mean 3.4 treatments per subject). There were no esophageal perforations. Strictures developed in 3 subjects. Two subjects reported severe chest pain managed with oral narcotics. One subject was hospitalized for bright red blood per rectum. Sixty subjects had completed all planned CRYO treatments and were included in the efficacy analysis. Fifty-eight subjects (97%) had complete eradication of HGD, 52 (87%) had complete eradication of all dysplasia with persistent nondysplastic intestinal metaplasia, and 34 (57%) had complete eradication of all intestinal metaplasia. Subsquamous BE was found in 2 subjects (3%). LIMITATIONS: Nonrandomized, retrospective study with no control group, short follow-up (10.5 months), lack of centralized pathology, and use of surrogate outcome for decreased cancer risk. CONCLUSIONS: CRYO is a safe and well-tolerated therapy for BE and HGD. Short-term results suggest that CRYO is highly effective in eradicating HGD.

Endoscopic spray cryotherapy for esophageal cancer: safety and efficacy.

BACKGROUND: Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies. OBJECTIVE: To assess the safety and efficacy of cryotherapy in esophageal carcinoma. DESIGN: Multicenter, retrospective cohort study. SETTING: Ten academic and community medical centers between 2006 and 2009. PATIENTS: Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy. INTERVENTIONS: Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition. MAIN OUTCOME MEASUREMENTS: Complete eradication of luminal cancer and adverse events. RESULTS: Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects. LIMITATIONS: Retrospective study design, short follow-up. CONCLUSIONS: Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer.

Double-balloon ERCP in patients who have undergone Roux-en-Y surgery: a case series.

BACKGROUND: ERCP is technically challenging in patients who have had a long-limb Roux-en-Y surgical procedure. The recent introduction of the double-balloon endoscope permits the examination of a much longer segment of the small bowel compared with a standard endoscope and may be used to perform ERCP in these patients. OBJECTIVE: To report successful use of double-balloon ERCP in patients who have had a Roux-en-Y surgical procedure. PATIENTS: Fourteen patients with a history of either Roux-en-Y gastric bypass weight-reduction surgery or Roux-en-Y pancreatobiliary surgery required diagnostic and/or therapeutic pancreatobiliary intervention. DESIGN: Case report. INTERVENTION: Double-balloon ERCP. RESULTS: Fourteen patients underwent a total of 20 ERCPs with the double-balloon endoscopy system. The ampulla was successfully reached in 85% of total cases (100% of patients who have had Roux-en-Y weight reduction surgery), with adequate cannulation of either the biliary or pancreatic duct in 80% (88% of patients for weight reduction). Therapeutic intervention, including stone removal, pancreatobiliary-duct dilation, sphincterotomy, stent placement, and removal of previously placed stents, was performed successfully in 6 cases. The mean age was 47 years old. The mean (+/- standard deviation) total duration of the procedure was 99 +/- 48 minutes. There were no immediate or short-term complications. CONCLUSIONS: The double-balloon endoscopy system permits diagnostic and therapeutic ERCP in patients who have had long-limb surgical procedures. Our experience demonstrated that this procedure is well tolerated, safe, and has a high success rate.

Management of ampullary lesions.

Adenomatous lesions of the ampulla of Vater are relatively rare neoplasms that raise many questions regarding standard management. Adenocarcinoma often will be found in ampullary lesions and should be treated by pancreaticoduodenectomy (PD). Benign-appearing adenomas may be treated by PD, transduodenal ampullectomy (AMP), or endoscopic ampullectomy (EA). AMP and EA have decreased morbidity and mortality compared with PD but are limited by concerns for appropriate resection margins, high recurrence rates, and the need for surveillance endoscopy or additional procedures. Preoperative endoscopic biopsies should be obtained to identify carcinoma, but they have high false-negative rates and cannot be relied upon to rule out malignancy. Intraoperative frozen section evaluation should be requested routinely during AMP, with conversion to PD if carcinoma is demonstrated. The gold standard management of benign adenomas has not been clarified, but the goal for all treatment modalities is complete resection. Patients with familial adenomatous polyposis may be exceptions to this, and routine surveillance endoscopy and biopsy with selective resection have been advocated by some as an alternative to complete resection. Adjuvant chemoradiation has a very limited role in the treatment of ampullary carcinoma and ideally should be offered in the setting of a clinical trial. Metastatic and locally advanced, unresectable lesions may be palliated by surgical or endoscopic bypass, as well as by celiac plexus blockade.

Usefulness of endoscopic ultrasound in patients at high risk of choledocholithiasis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been considered the nonsurgical gold standard for the diagnosis and treatment of choledocholithiasis (CDL). Complications include a 0.1% to 1.3% mortality rate and a 5% to 19% morbidity rate, including a reported 1.8% to 6.7% incidence of postprocedure pancreatitis. Twenty-seven percent to 67% of ERCPs done for suspected choledocholithiasis ultimately have negative results. Endoscopic ultrasound (EUS) has been proposed as an alternate means of diagnosing choledocholithiasis that may eliminate the need for ERCP and its associated morbidities in certain patients. METHODS: Retrospective chart review identified 30 patients who underwent EUS with or without ERCP for suspected choledocholithiasis. Reports of all procedures performed were obtained and data were collected on all biliary abnormalities identified on both EUS and ERCP. RESULTS: Pancreaticobiliary abnormalities were identified in 27 of 30 patients (90%) at EUS. Most common diagnoses included CDL (n = 9, 30%), biliary sludge (n = 11, 37%), pancreatitis (n = 8, 27%), and cholelithiasis (n = 7, 23%). Subsequent ERCP was performed in 14 patients (47%). Indications included a diagnosis of CDL by EUS (n = 9) and abnormal liver function tests (n = 5). CDL was identified in 5 of 14 patients (36%), and microlithiasis/biliary sludge was identified in an additional 5 patients (36%). In 4 patients, CDL was identified by EUS but not by ERCP. ERCP did not identify any new cases of CDL after EUS: of 21 patients without evidence of CDL on EUS, none were subsequently shown to have CDL or to develop any complications related to common duct stones. CONCLUSIONS: EUS is an effective method of diagnosing CDL. It demonstrates both a high sensitivity and specificity for identifying common bile duct stones. Its use as a screening modality in patients suspected of having CDL may allow more selective use of ERCP.

Management of the single liver nodule in a cirrhotic patient: a decision analysis model.

The widespread use of liver imaging in patients with cirrhosis results in the discovery of small (<3 cm) nodules. Although the subsequent management of these patients is variable, it is generally focused on the diagnosis and treatment of hepatocellular carcinoma (HCC). We aimed to compare the 3-year survival associated with several competing strategies used in the management of patients with compensated liver cirrhosis in whom a single small liver lesion is detected during surveillance. We constructed a decision analysis model using a decision tree and Markov model. We assumed that all patients undergo an initial "diagnostic phase" consisting of an imaging study and serum alpha-fetoprotein (AFP). Patients with a "positive initial diagnostic phase" for HCC are referred for either imaging-guided biopsy (IGB) or surgical resection or orthotopic liver transplantation (OLT) without preceding IGB. IGB, if positive for HCC, was followed by OLT, surgical resection, or local therapy. Patients with a "negative initial diagnostic phase" undergo either repeat diagnostic testing (imaging, AFP) every 4 months or are referred for either OLT, surgical resection, or IGB followed by interventions. Probability assumptions were estimated from the published literature. The outcomes compared were 3-year overall survival and recurrence-free survival. When the initial diagnostic phase is positive for HCC, OLT it is associated with the longest survival. In the sensitivity analysis, when the 3-year overall survival for patients referred to OLT is <54%, surgical resection or IGB preceding therapy become more favorable strategies. This 3-year overall survival (<54%) associated with OLT is reached after a waiting time of 4 months on the transplant list, if a 4% monthly dropout rate is assumed. When the initial diagnostic phase is negative for HCC, then performing IGB, before proceeding to therapeutic intervention, is associated with the longest 3-year overall survival. If the IGB is positive, subsequent OLT is associated with the longest survival. The higher the predictive value of the initial diagnostic phase for HCC, the more favorable is OLT (for the "positive results" arm), and follow-up testing (for the "negative results" arm). In conclusion, given a high pretest likelihood of HCC in a single liver nodule detected during surveillance in patients with cirrhosis, IGB may not be required in the presence of a positive noninvasive diagnostic testing. The long waiting time prior to OLT limits its advantage over surgical resection in the treatment of patients with early HCC.