Role of endoscopic ultrasound in pancreatic diseases: a systematic review.

AIM: Since its introduction, endoscopic ultrasonography (EUS) has been increasingly gaining more attention for diagnosing various gastrointestinal conditions. We aim to systematically review the literature and highlight the benefit of using EUS in different pancreatic diseases by primarily reviewing its importance in diagnosing, treating pancreatic pathologies, comparing its accuracy to other modalities and determining its limitations and complications. METHODS: Using defined (MeSH) terms and keywords; two reviewers conducted a MEDLINE search through August 2014, in addition to manually searching relevant bibliographies cited in the included studies. All case reports, case series, letters, non-English and non-human articles were excluded. RESULTS: Total of (N.=2144) potentially relevant citations were identified and screened, of which (N.=525) fulfilled eligibility criteria and grouped into seven pancreatic disease categories: chronic pancreatitis (N.=72), acute pancreatitis (N.=75), autoimmune pancreatitis (N.=31), pancreatic cancer (N.=179), neuroendocrine pancreatic tumors (N.=48), pancreatic cysts (N.=111) and pancreatic divisum (N.=9). CONCLUSION: EUS sensitivity to diagnose chronic pancreatitis is greater than endoscopic retrograde cholangiopancreatography and CT, but using EUS-guided fine needle aspiration (EUS-FNA) is not diagnostic. In acute biliary pancreatitis, EUS is superior to CT and to magnetic resonance cholangiopancreatography (MRCP) for detection of microlithiasis. EUS-guided pseudocyst drainage is safe with a high success rate. Contrast-enhanced EUS is more valuable than EUS in autoimmune pancreatitis and EUS-FNA is not recommended. EUS is superior to MRCP and multiple detector CT in evaluating pancreatic divisum. Cystic carcinoembryonic antigen level obtained using EUS-FNA is the most accurate test to exclude malignant pancreatic cyst.

Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma.

BACKGROUND: Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma (PDAC) but no standard of care exists. Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging preclinical activity in PDAC. We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT) as neoadjuvant therapy in patients with localized or locally advanced PDAC. EXPERIMENTAL DESIGN: Treatment consisted of cetuximab load at 400 mg/m(2) followed by cetuximab 250 mg/m(2) weekly and gemcitabine 50 mg/m(2) twice-weekly given concurrently with IMRT to 54 Gy. Following therapy, patients were considered for resection. RESULTS: Thirty-seven patients were enrolled with 33 assessable for response. Ten patients (30%) manifested partial response and 20 (61%) manifested stable disease by RECIST. Twenty-five patients (76%) underwent resection, including 18/23 previously borderline and 3/6 previously unresectable tumors. Twenty-three (92%) of these had negative surgical margins. Pathology revealed that 24% of resected tumors had grade III/IV tumor kill, including two pathological complete responses (8%). Median survival was 24.3 months in resected patients. Outcome did not vary by epidermal growth factor receptor status. CONCLUSIONS: Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC. Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival. Pathological complete responses can occur. This combination warrants further investigation.

Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States.

BACKGROUND: Effectiveness of medical therapies in chronic pancreatitis has been described in small studies of selected patients. AIM: To describe frequency and perceived effectiveness of non-analgesic medical therapies in chronic pancreatitis patients evaluated at US referral centres. METHODS: Using data on 516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we evaluated how often medical therapies [pancreatic enzyme replacement therapy (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB)] were utilized and considered useful by physicians. RESULTS: Oral PERT was commonly used (70%), more frequently in the presence of exocrine insufficiency (EI) (88% vs. 61%, P < 0.001) and pain (74% vs. 59%, P < 0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87-9.18), constant (OR 3.42, 95% CI 1.93-6.04) or intermittent pain (OR 1.98, 95% CI 1.14-3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36-3.42). AO were tried less often (14%) and were more effective in idiopathic and obstructive vs. alcoholic chronic pancreatitis (25% vs. 4%, P = 0.03). Other therapies were infrequently used (CPB - 5%, octreotide - 7%) with efficacy generally <50%. CONCLUSIONS: Pancreatic enzyme replacement therapy is commonly utilized, but is considered useful in only subsets of chronic pancreatitis patients. Other medical therapies are used infrequently and have limited efficacy.

Systematic review: efficacy and safety of pancreatic enzyme supplements for exocrine pancreatic insufficiency.

BACKGROUND: Pancreatic enzyme supplements are standard therapy for fat malabsorption in patients with exocrine pancreatic insufficiency. The FDA determined that published data are insufficient to support the efficacy and safety of these agents. AIM: To determine if pancreatic enzyme supplements are: (i) superior to placebo for treating fat malabsorption and (ii) superior to other supplements based on randomized cross-over trials. METHODS: A computer-assisted search of MEDLINE and EMBASE was performed to identify relevant studies. Data extraction on study design, improvement in coefficient of fat absorption, diarrhoea and adverse events using prespecified forms. RESULTS: A total of 12 manuscripts met inclusion criteria. Most studies (10/12) compared pancreatic enzyme supplements that used different delivery systems, while using similar quantities of enzymes. These studies found no consistent difference in fat malabsorption or gastrointestinal symptoms between different active treatments. Two small placebo-controlled trials (n = 65 patients) demonstrate that pancreatic enzyme supplements are superior to placebo for fat absorption. Data are inadequate to determine if pancreatic enzyme supplements lead to weight gain or improvement in diarrhoea. CONCLUSIONS: Based on data from randomized cross-over trials, pancreatic enzyme supplements appear to improve fat malabsorption. No specific branded product or specific delivery system is superior for treatment of fat malabsorption in patients with exocrine pancreatic insufficiency.

Endoscopic ultrasonography and pancreatic cancer.

Despite extensive multidisciplinary efforts, the five-year survival rate for all patients with pancreatic adenocarcinoma remains less than 3%. In the last twenty years, endoscopic ultrasound (EUS) has developed into an indispensable tool for the diagnosis and staging of malignant pancreatic lesions. EUS, in combination with helical and multidetector computed tomography scans, is currently 80-90% accurate in determining the tumor TNM stage. EUS fine-needle aspiration obtains diagnostic pathologic samples in approximately 80% of cases, and intraductal ultrasound has augmented the ability to determine the malignant potential of pancreatic strictures. In patients at high-risk for pancreatic malignancy, EUS has been advocated as a screening tool for malignancy. Finally, exciting new developments suggest the potential of EUS as a therapeutic tool, both for the management of pain from pancreatic cancer and as a novel therapeutic-delivery device.

Two cases of rapid onset Parkinson's syndrome following toxic ingestion of ethylene glycol and methanol.

Ethylene glycol and methanol are toxic alcohols commonly found in a variety of commercial products. We report two cases, one associated with ethylene glycol and one with methanol poisoning, which both led to acute hemorrhagic necrosis of the basal ganglia and resulted in acute Parkinson's syndrome. It is unlikely that oxalate crystal deposition is the only mechanism for such basal ganglia necrosis, because similar findings were seen following methanol intoxication. We discuss other possible mechanisms that may contribute towards this unusual neurotoxicity. Both of our patients survived their toxic ingestions, but then developed acute Parkinson's syndrome within 10 days of the ingestion. However, the patient who ingested methanol developed respiratory muscle stiffness/weakness, which responded poorly to anti-Parkinsonian drug therapy. Treatment with carbidopa/levodopa improved cogwheel rigidity and bradykinesia in both patients. We conclude that acute Parkinsonism is one of the lesser-recognized devastating complications of both ethylene glycol and methanol poisoning.

Treatment of giardiasis.

Giardia lamblia is both the most common intestinal parasite in the United States and a frequent cause of diarrheal illness throughout the world. In spite of its recognition as an important human pathogen, there have been relatively few agents used in therapy. This paper discusses each class of drugs used in treatment, along with their mechanism of action, in vitro and clinical efficacy, and side effects and contraindications. Recommendations are made for the preferred treatment in different clinical situations. The greatest clinical experience is with the nitroimidazole drugs, i.e., metronidazole, tinidazole, and ornidazole, which are highly effective. A 5- to 7-day course of metronidazole can be expected to cure over 90% of individuals, and a single dose of tinidazole or ornidazole will cure a similar number. Quinacrine, which is no longer produced in the United States, has excellent efficacy but may be poorly tolerated, especially in children. Furazolidone is an effective alternative but must be administered four times a day for 7 to 10 days. Paromomycin may be used during early pregnancy, because it is not systematically absorbed, but it is not always effective. Patients who have resistant infection can usually be cured by a prolonged course of treatment with a combination of a nitroimidazole with quinacrine.

Knowledge of travel medicine providers: analysis from a continuing education course.

BACKGROUND: With millions of international travelers, there has been an increase in the scope and variability of travel medicine providers. A study was conducted to measure the baseline knowledge of providers, determine factors affecting this knowledge, and assess acquisition of knowledge after a continuing education course. METHODS: A one-day continuing medical education course was held for health care professionals interested in travel medicine. Prior to the course, attendees completed a test determining knowledge in malaria chemoprophylaxis, traveler's diarrhea management, vaccines, jet lag, the returned traveler, and other areas. An identical test was given after completion of the course. Performance on the test was analyzed by profession, area of specialty training, and experience in travel medicine. RESULTS: Seventy-seven attendees completed the precourse test. Forty-eight percent were physicians and 47% were nurses; 29% specialized in infectious diseases, 22% in occupational medicine and student health, and 18% in family or internal medicine; 60% had >/= 1 year of travel medicine experience while 20% had no experience. The precourse test score for all participants was 62.7% 6 6.5 (sd). Analysis by profession found that physicians scored the highest (71%). Providers with >/= 1 year of travel medicine experience scored higher than those with no experience (67% vs 53%, p <.01). Statistically significant correlations were found between precourse exam results and profession (+.432, p <.001) and travel medicine experience (+.365, p =.002). No significant correlation was found between precourse exam and area of specialty training. Combined mean score on the postcourse exam improved to 81.8% 6 4.5, an increase of 17.2% over the precourse score for those who took both tests (p <.001). CONCLUSIONS: The profession of the provider and the duration of experience in travel medicine were the most important correlations of baseline knowledge in travel medicine. All groups improved their knowledge following the course.