High-risk symptoms do not predict gastric cancer precursors.

BACKGROUND & STUDY AIMS: Gastric intestinal metaplasia (GIM) is the most common precursor of gastric cancer. Our aim is to determine if presenting symptoms predict gastric cancer precursor lesions in a high-risk population. PATIENT AND METHODS: Consecutive unique patients evaluated by endoscopy for upper gastrointestinal symptoms at the Los Angeles County Hospital between 2010 and 2014 were evaluated. Presenting symptoms were classified as low- or high-risk depending on the procedure indication as coded using the Clinical Outcomes Research Initiative (CORI) system. Endoscopy and histology results were used to classify findings as benign, GIM, high-risk GIM, or malignant. The primary outcome was the proportion of patients with premalignant or malignant gastric findings who had high-risk clinical indications for endoscopy relative to those with benign results. RESULTS: A total of 3699 patients underwent endoscopy to evaluate upper gastrointestinal symptoms. There were 373 (10.1%) patients with GIM of which 278 had high-risk GIM. One hundred and sixty (4.3%) patients were diagnosed with gastric cancer. High-risk indications for upper endoscopy predicted gastric cancer (OR 1.8 [95% CI 1.3-2.6]) but not GIM (OR 1.0 [0.8-1.3]) or high-risk GIM (OR 0.9 [0.7-1.2]). Hispanic or Asian patients and patients >50 years old were more likely to have GIM, high-risk GIM, and cancer. CONCLUSIONS: Performance of upper endoscopy for high-risk indications is inadequate to detect GIM and marginal for malignancy. At risk patients should undergo upper endoscopy for both low- and high-risk symptoms. Screening certain populations deserve additional study and may, in fact, be cost-effective.

Dynamic liver test patterns do not predict bile duct stones.

BACKGROUND: Numerous models have been developed to predict choledocholithiasis. Recent work has shown that these algorithms perform suboptimally. Identification of clinical predictors with high positive and negative predictive value would minimize adverse events associated with unnecessary diagnostic endoscopic retrograde cholangiopancreatography (ERCP) while limiting the use of expensive tests including magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) for indeterminate cases. METHODS: Consecutive unique inpatients who received their first ERCP at Los Angeles County Medical Center between January 2010 and November 2016 for suspected bile duct stones were reviewed. The primary outcome was the proportion of patients with specific combinations of liver enzyme patterns, transabdominal ultrasound, and clinical features who had stones confirmed on ERCP. As a secondary outcome, we assessed the performance of the American Society for Gastrointestinal Endoscopy (ASGE) risk stratification algorithm in our population. RESULTS: Of the 604 included patients, bile duct stones were confirmed in 410 (67.9%). Detailed assessment of liver enzyme patterns alone and in combination with clinical features and imaging findings yielded no highly predictive algorithms. Additionally, the ASGE high-risk criterion had a positive predictive value of only 68% for stones. For the 236 patients for whom MRCP was performed, this imaging modality was shown to have highest predictive value for the presence of stones on ERCP. CONCLUSION: Exhaustive exploration of various threshold values and dynamic patterns of liver enzymes combined with clinical features and basic imaging findings did not reveal an algorithm to accurately predict the presence of stones on ERCP. The ASGE risk stratification criteria were also insensitive in our population. Though desirable, there may be no "perfect" combination of clinical features that correlate with persistent bile duct stones. MRCP or EUS may be considered to avoid unnecessary ERCP and associated complications.

Early Aggressive Hydration Hastens Clinical Improvement in Mild Acute Pancreatitis.

OBJECTIVES: Early aggressive intravenous hydration is recommended for acute pancreatitis treatment although randomized trials have not documented benefit. We performed a randomized trial of aggressive vs. standard hydration in the initial management of mild acute pancreatitis. METHODS: Sixty patients with acute pancreatitis without systemic inflammatory response syndrome (SIRS) or organ failure were randomized within 4 h of diagnosis to aggressive (20 ml/kg bolus followed by 3 ml/kg/h) vs. standard (10 ml/kg bolus followed by 1.5 mg/kg/h) hydration with Lactated Ringer's solution. Patients were assessed at 12-h intervals. At each interval, in both groups, if hematocrit, blood urea nitrogen (BUN), or creatinine was increased, a bolus of 20 ml/kg followed by 3 ml/kg/h was given; if labs were decreased and epigastric pain was decreased (measured on 0-10 visual analog scale), hydration was then given at 1.5 ml/kg/h and clear liquid diet was started. The primary endpoint, clinical improvement within 36 h, was defined as the combination of decreased hematocrit, BUN, and creatinine; improved pain; and tolerance of oral diet. RESULTS: The mean age of the patients was 45 years and only 14 (23%) had comorbidities. A higher proportion of patients treated with aggressive vs. standard hydration showed clinical improvement at 36 h: 70 vs. 42% (P=0.03). The rate of clinical improvement was greater with aggressive vs. standard hydration by Cox regression analysis: adjusted hazard ratio=2.32, 95% confidence interval 1.21-4.45. Persistent SIRS occurred less commonly with aggressive hydration (7.4 vs. 21.1%; adjusted odds ratio (OR)=0.12, 0.02-0.94) as did hemoconcentration (11.1 vs. 36.4%, adjusted OR=0.08, 0.01-0.49). No patients developed signs of volume overload. CONCLUSIONS: Early aggressive intravenous hydration with Lactated Ringer's solution hastens clinical improvement in patients with mild acute pancreatitis.

Validation of a clinical prediction scale for hospital-onset Clostridium difficile infection.

OBJECTIVE: The aim of this study was to validate a clinical prediction scale for hospital-onset Clostridium difficile infection (CDI). METHODS: The study included a consecutive cohort of patients admitted to the adult medical service over a period of 17 months (June 2011 to October 2012). The clinical prediction scale comprised of new-onset loose stools (5 points), length of hospital stay >7days (4 points), aged 65 years or older (3 points), resides in long-term care facility (2 points), broad spectrum antibiotics use (1 point), and hypoalbuminemia (1 point). The hospital-onset CDI cases were defined as any new-onset diarrhea after 48 hours of hospital admission that tested positive on polymerase chain reaction assay for C. difficile toxin gene in the absence of history of CDI in the prior 8 weeks. The predictive performance of the scale was assessed using area under the receiver operating curve. RESULTS: A total of 10,357 patients were admitted to the medical service, of which, 7026 stayed in hospital beyond 48 hours. Mean (SD) age was 68.5 (18.2) years and 41.9% patients were male. A total of 1030 patients were tested for C. difficile toxin gene using polymerase chain reaction assay, of which, 159 patients were positive and 62 of them were unique hospital-onset CDI cases. The scale had area under the receiver operating curve of 0.94 [95% confidence interval (CI), 0.92-0.95]. At the cutoff score of 9, scale was 98.3% (95% CI, 90.2-99.9) sensitive and 85.2% (95% CI, 84.3-86.0) specific. CONCLUSIONS: Our study results support excellent predictive performance of a clinical prediction scale for hospital-onset CDI. This simple scale can be used in risk stratification leading to prompt tailoring of modifiable risk factors, empirical treatment, and use of probiotics.

A cohort study for derivation and validation of a clinical prediction scale for hospital-onset Clostridium difficile infection.

OBJECTIVE: To develop and validate a clinical prediction scale for hospital-onset Clostridium difficile infection (CDI). METHODS: A community-based, 360-bed hospital located in the suburbs of a metropolitan area in the United States served as the setting for the present retrospective cohort study. The cohort consisted of patients admitted to the adult medical service over a six-year period from October 2005 to September 2011. The cohort was divided into derivation (October 2005 to September 2009) and validation (October 2009 to September 2011) groups. The primary outcome measure was hospital-onset CDIs identified as stool positive for C difficile after 48 h of hospital admission ordered for new-onset unformed stool by the treating physician. RESULTS: In the derivation phase, 35,588 patients were admitted to the medical service and 21,541 stayed in hospital beyond 48 h. A total of 266 cases of CDI were identified, 121 of which were hospital onset. The developed clinical prediction scale included the onset of unformed stool (5 points), length of hospital stay beyond seven days (4 points), age >65 years (3 points), long-term care facility residence (2 points), high-risk antibiotic use (1 point) and hypoalbuminemia (1 point). The scale had an area under the receiver operating curve (AUC) of 0.93 (95% CI 0.82 to 0.94) in predicting hospital-onset CDI, with a sensitivity of 0.94 (95% CI 0.88 to 0.97) and a specificity of 0.80 (95% CI 0.79 to 0.80) at a cut-off score of 9 on the scale. During the validation phase, 16,477 patients were admitted, of whom 10,793 stayed beyond 48 h and 58 acquired CDI during hospitalization. The predictive performance of the score was maintained in the validation cohort (AUC 0.95 [95% CI 0.93 to 0.96]) and the goodness-to-fit model demonstrated good calibration. CONCLUSION: The authors developed and validated a simple clinical prediction scale for hospital-onset CDI. This score can be used for periodical evaluation of hospitalized patients for early initiation of contact precautions and empirical treatment once it is validated externally in a prospective manner.

Rare cause of gastric outlet obstruction.

Bouveret's syndrome is a rare cause of gastric outlet obstruction. The stones enter the small bowel via cholecysto-enteric fistula. The most common presenting symptoms are abdominal pain, nausea and vomiting. The gold standard diagnostic test isesophagogastroduodenoscopy (EGD). Rigler's triad on abdominal x-ray is classic. CT scan findings are pneumobilia, cholecystoduodenal fistula and a gallstone in the duodenum. We present a case of a 75-year-old female who presents with 3 week history of nausea, vomiting, and diffuse abdominal pain. Initial presentation, imaging and EGD was concerning for malignancy. She was later diagnosed to have Bouveret's syndrome and underwent laparoscopic small bowel enterotomy with removal of gallstones.

A case of recurrent obscure gastrointestinal bleeding: Heyde's syndrome - case report and review.

Gastrointestinal bleeding from angiodysplasias in patients with aortic stenosis is termed as 'Heyde's syndrome'. We report a case of Heyde's syndrome successfully treated with trans-catheter aortic valve replacement.

Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease.

Although the general association of the inflammatory bowel disease (IBD) 5 region on chromosome 5q31 to Crohn's disease (CD) has been replicated repeatedly, the identity of the precise causal variant within the region remains unknown. A recent report proposed polymorphisms in solute carrier family 22, member 4 (SLC22A4) organic cation transporter 1(OCTN1) and solute carrier family 22, member 5 (SLC22A5) (OCTN2) as responsible for the IBD5 association, but definitive, large-sample comparison of those polymorphisms with others known to be in strong linkage disequilibrium was not performed. We evaluated 1879 affected offspring and parents ascertained by a North American IBD Genetics Consortium for six IBD5 tag single nucleotide polymorphisms (SNPs) to evaluate association localization and ethnic and subphenotypic specificity. We confirm association to the IBD5 region (best SNP IGR2096a_1/rs12521868, P<0.0005) and show this association to be exclusive to the non-Jewish (NJ) population (P=0.00005) (risk allele undertransmitted in Ashkenazi Jews). Using Phase II HapMap data, we demonstrate that there are a set of polymorphisms, spanning genes from prolyl 4-hydroxylase (P4HA2) through interferon regulatory factor 1 (IRF1) with equivalent statistical evidence of association to the reported SLC22A4 variant and that each, by itself, could entirely explain the IBD5 association to CD. Additionally, the previously reported SLC22A5 SNP is rejected as the potential causal variant. No specificity of association was seen with respect to disease type and location, and a modest association to ulcerative colitis is also observed. We confirm the importance of IBD5 to CD susceptibility, demonstrate that the locus may play a role in NJ individuals only, and establish that IRF1, PDLIM, and P4HA2 may be equally as likely to contain the IBD5 causal variant as the OCTN genes.

Autoimmune pancreatitis and cholangitis.

Autoimmune pancreatitis (AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4 (IgG4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreatic manifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.

Hypergastrinemia and recurrent type 1 gastric carcinoid in a young Indian male: necessity for antrectomy?

Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the widespread use of Esophagogastroduodenoscopy for evaluating a variety of upper gastrointestinal symptoms, the detection of early gastric carcinoids has increased. We highlight an alternative management of a young patient with recurrent type 1 gastric carcinoids with greater than 5 lesions, as well as lesions intermittently greater than 1 cm. Gastric carcinoids have a variable presentation and clinical course that is highly dependent on type. Type 1 gastric carcinoids are usually indolent and have a metastasis rate of less than 2%, even with tumors larger than 2 cm. There are a number of experts as well as organizations that recommend endoscopic resection for all type 1 gastric carcinoid lesions less than 1 cm, with a follow-up every 6-12 mo. They also recommend antrectomy for type 1 gastric carcinoids with greater than 5 lesions, lesions 1 cm or greater, or refractory anemia. However, the American Society of Gastrointestinal Endoscopy guidelines state that type 1 gastric carcinoid surveillance is controversial based on the evidence and could not make an evidence-based position statement on the best treatment modality. Our report illustrates a rare cause of iron deficiency anemia in a young male (without any medical history) due to multiple recurrent gastric carcinoid type 1 lesions in the setting of atrophic gastritis causing hypergastrinemia, and in the absence of a vitamin B12 deficiency. Gastric carcinoid type 1 can present in young males without an autoimmune history, despite the known predilection for women aged 50 to 70 years. Type 1 gastric carcinoids can be managed by endoscopic resection in patients with greater than 5 lesions, even with lesions larger than 1 cm. This course of treatment enabled the avoidance of early antrectomy in our patient, who expressed a preference against more invasive measures at his young age.

Diagnosis and management of cystic lesions of the pancreas.

Pancreatic cysts are challenging lesions to diagnose and to treat. Determining which of the five most common diagnoses-pancreatic pseudocyst, serous cystic neoplasm (SCN), solid pseudopapillary neoplasm (SPN), mucinous cystic neoplasm (MCN), and intraductal mucinous papillary neoplasm (IPMN)-is likely the correct one requires the careful integration of many historical, radiographic, laboratory, and other factors, and management is markedly different depending on the type of cystic lesion of the pancreas. Pseudocysts are generally distinguishable based on historical, clinical and radiographic characteristics, and among the others, the most important differentiation is between the mucin-producing MCN and IPMN (high risk for cancer) versus the serous SCN and SPN (low risk for cancer). EUS with FNA and cyst-fluid analysis will continue to play an important role in diagnosis. Among mucinous lesions, those that require treatment (resection currently) are any MCN, any MD IPMN, and BD IPMN larger than 3 cm, symptomatic, or with an associated mass, with the understanding that SCN or pseudocysts may be removed inadvertently due to diagnostic inaccuracy, and that a certain proportion of SPN will indeed be malignant at the time of removal. The role of ethanol ablation is under investigation as an alternative to resection in selected patients.

Role of endoscopic ultrasound/SpyScope in diagnosis and treatment of choledocholithiasis in pregnancy.

Cholelithiasis and choledocholithiasis occur frequently in pregnancy and their management can be complicated. Traditional endoscopic retrograde cholangiopancreatography (ERCP) is the first line treatment for choledocholithiasis, but in addition to its baseline risks, fluoroscopy poses an additional radiation risk to the fetus. Endoscopic ultrasound (EUS) is an accurate modality for detecting common bile duct stones, but its role has not been defined in pregnancy. We describe an alternative management strategy to conventional ERCP in a pregnant patient with choledocholithiasis and cholangitis detected using EUS and choledochoscopy.

Metastatic Renal Cell Cancer and a Gastric Mass: An Unusual Finding.

Renal cell cancer (RCC) accounts for approximately 3% of all adult malignancies. RCC has a metastasis rate of approximately 25%, which is most commonly to the lungs (>50%). On the contrary, RCC metastasis to the gastrointestinal tract (excluding the liver) is very uncommon and ranges from 0.2 to 0.7%. Thus, a gastric cancer in a patient with known metastatic RCC would most likely be secondary to metastasis. We present the first reported case of a metastatic RCC coexisting with a new-onset primary gastric cancer and a review of management using guidelines from metastatic RCC to the stomach. An 82-year-old African American male with papillary RCC status post left nephrectomy with recurrence of liver metastasis presented with failure to thrive shortly after his third cycle of chemotherapy despite stable disease by imaging studies. He had received 7 chemotherapy cycles of Gemzar, Nexavar, and Avastin prior to admission. He subsequently had a drop in his hemoglobin and was found to have hemoccult positive stool in the setting of recent Avastin. Endoscopic evaluation showed a 3 cm ulcerated mass in the cardia which was biopsied. The biopsy showed invasive and poorly differentiated gastric adenocarcinoma unrelated to his RCC. The patient subsequently underwent partial gastrectomy with loop gastrojejunostomy for resection of his stage 1 primary gastric adenocarcioma. The surgery also facilitated future chemotherapy (Avastin), which could not be given prior to surgery due to its side effect of bleeding. The patient did not receive adjuvant chemoradiation for his gastric cancer due to his comorbidities at the time and was doing well at a one month follow-up. Metastatic RCC and primary gastric cancer can coexist, especially when there is an overlap of risk factors such as smoking or nitrosamines. The management of a gastric cancer in the setting of metastatic RCC is similar to the management of solitary primary gastric carcinoma. Treatment of the primary gastric cancer can facilitate future chemotherapy such as Avastin, which has been recently approved for the treatment of metastatic RCC.

EUS-guided FNA diagnosis of pancreatic endocrine tumors: new trends identified.

BACKGROUND: Pancreatic endocrine tumors (PETs) are rare (1 per 100,000 population) and are thought to be functioning in up to 85% of cases and are generally less than 2 cm in size. By previous reports, 15% to 50% of PETs are nonfunctioning and are discovered either incidentally or by symptom evaluation from a mass effect. EUS-guided FNA (EUS-FNA) has been shown to accurately diagnose PETs and to localize tumors for surgical resection. OBJECTIVE: To describe a single-center experience of EUS-FNA diagnosis of PETs and its impact on surgical management. DESIGN: Retrospective cohort study. SETTING: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. PATIENTS: Patients with PETs diagnosed via EUS-FNA over a 4-year period were identified through the authors' EUS database. Clinical history, laboratory values, diagnostic studies, EUS findings, cytology, pathology, operative records, and surgical pathology records were reviewed. MAIN OUTCOME MEASUREMENT: Impact of definitive preoperative diagnosis of PET on surgical management. RESULTS: Forty-one patients were diagnosed by EUS-FNA with PET. Thirty-five PETs were nonfunctioning PET; 6 were functioning PET. The mean tumor sizes of functioning and nonfunctioning PETs were 19 mm and 28 mm, respectively. The majority of tumors were located in the pancreatic head. Surgery was performed in 78% of patients; of these, 34% were resected laparoscopipcally. LIMITATIONS: Retrospective design and selection bias. CONCLUSIONS: In this study, nonfunctioning PETs were more commonly diagnosed compared with functioning PETs. In addition, the PETs were smaller than previously reported, likely because of increasing detection of incidental lesions through widespread use of abdominal imaging.

Pancreatic endocrine tumors.

Incidental, nonfunctional pancreatic endocrine tumors (PET) are observed with increasing frequency. Most are insulinomas. Endoscopic ultrasound with fine-needle aspiration plays a significant role in the localization and tissue diagnosis of PET. Establishing PET behavior as aggressive or indolent remains challenging especially preoperatively. Newer techniques including DNA and micro-RNA analysis may play a role in this arena. Small benign PET may be enucleated or removed laparoscopically. Surgery is the mainstay of treating advanced disease including those with metastases and Zollinger-Ellison syndrome. The management of multiple endocrine neoplasia type 1 continues to be a challenge, including treating symptoms, targeted resections, and close observation. Diagnosis, management, and prognostication of PET are under evolution and a number of changes in these fronts are anticipated.

Endoscopic ultrasound-guided fine needle aspirate microsatellite loss analysis and pancreatic endocrine tumor outcome.

BACKGROUND & AIMS: The clinical course of pancreatic endocrine tumor (PET) varies depending on tumor aggressiveness, disease extent, and possibly accumulated molecular alterations. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) results, although accurate in diagnosing PET, correlate poorly with PET outcome. The role of detecting key molecular abnormalities in predicting PET behavior and clinical outcome from EUS-FNA material remains unknown. METHODS: Patients with confirmed PET who underwent EUS-FNA during a 32-month period were included. Patient demographics and clinical data were recorded and follow-up information was obtained by contacting their physician to evaluate disease progression. Representative tumor cells were microdissected from the FNA material. DNA was harvested and amplified, targeting a panel of 17 polymorphic microsatellite markers on chromosomes 1p, 3p, 5q, 9p, 10q, 11q, 17p, 17q, 21q, and 22q. The polymerase chain reaction products were subjected to fluorescent capillary gel electrophoresis to detect microsatellite loss. The fractional allelic loss (FAL) was calculated. RESULTS: Twenty-five patients were studied. Thirteen were classified histologically as benign PET limited to the pancreas and 12 as malignant PET (invasive or metastatic). The mean FAL in the benign and malignant PET was 0.03 and 0.37 (P<.0001), respectively. In addition, the mean FAL was significantly greater in those with disease progression as compared with patients with stable disease (0.45 vs 0.09 respectively, P<.0001). CONCLUSIONS: Microsatellite loss analysis of EUS-FNA material from PET can be performed reliably and an FAL value of more than 0.2 is associated with disease progression. This technique may have value in the preoperative assessment and risk stratification of patients with PET.