Pancreas Cancer Incidence and Pancreas Cancer-Associated Mortality Are Low in National Cohort of 7211 Pancreas Cyst Patients.

BACKGROUND AND AIMS: Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period. METHODS: We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999-2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality. RESULTS: Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4 years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths). CONCLUSIONS: Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance.

Abdominal free fluid in acute pancreatitis predicts necrotizing pancreatitis and organ failure.

BACKGROUND: Abdominal free fluid is frequently encountered on cross-sectional imaging for acute pancreatitis and may be a sign of increased severity and complications. This study examines the ability of free fluid to predict necrotizing pancreatitis and other adverse outcomes. METHODS: We conducted a single-center retrospective study of patients with acute pancreatitis and multiple cross-sectional imaging studies. Patients were divided into those who demonstrated free fluid on initial imaging and those without free fluid. The primary outcome was developing necrotizing pancreatitis. Logistic regression analysis assessed the performance of several predictors. RESULTS: A total of 245 acute pancreatitis patients were included. Pancreatic necrosis occurred more frequently in the free fluid group (31.3 vs. 1.3%, P<0.001). The free fluid group also had higher rates of transient organ failure (17.7 vs. 3.4%, P<0.001), persistent organ failure (17.7 vs. 2.0%, P<0.001), in-hospital mortality (7.3 vs. 1.3%, P=0.016), length of stay (16.2 vs. 5.5 days, P<0.001), and intensive care unit admission (30.2 vs. 4.7%, P<0.001). On multivariate logistic regression, free fluid was the strongest predictor (adjusted odds ratio 17.11, 95% confidence interval 3.68-79.65; P<0.001) for necrotizing pancreatitis, with an excellent performance (area under the curve 0.92). When neither fluid on initial imaging nor persistent systemic inflammatory response syndrome was present, the negative predictive value for developing pancreatic necrosis was 100%. CONCLUSIONS: Free fluid in acute pancreatitis is a strong predictor for necrotizing pancreatitis, organ failure and mortality, and outperformed current predictors. Patients who lacked both free fluid on imaging and persistent systemic inflammatory response syndrome are at low risk for adverse outcomes and may be considered for early discharge.

Rectal endometriosis mimicking primary rectal adenocarcinoma.

Endometriosis is a benign entity defined as the presence of endometrium tissue outside of uterine cavity. It is a common disease involving peritoneum, pelvic organs, gastrointestinal tract, and so on. Diagnosis based on cytology specimen can be challenge when we encounter increased cytological atypia in the glandular epithelium, with abundant inflammatory cells and debris in the background. We presented a case of deep rectal endometriosis mimicking rectal adenocarcinoma on cytology specimen and on MRI imaging studies. The combination of endometrial glands, cellular Mullerian stroma, hemorrhage, and hemosiderin-laden macrophages are the characteristic features on cytologic specimens.

Endoscopic ultrasound: a powerful tool to modify treatment algorithms in opioid-induced achalasia.

BACKGROUND: Opioid use in the U.S. has increased dramatically over the last 15 years, recently being declared a public health emergency. Opioid use is associated with esophageal dysmotility lending to a confusing clinical picture compared to true achalasia. Patients exhibit symptoms and elicit diagnostic results consistent with esophageal motility disorders, in particular type III achalasia. Modified therapeutic strategies and outcomes become challenging. Differentiating true achalasia from opioid-induced achalasia is critical. Conventional surgical interventions, i.e., myotomy, are ineffective in the absence of true achalasia. We assess the utility of esophageal muscle layer mapping with endoscopic ultrasound (EUS) in distinguishing primary from opioid-induced achalasia. METHODS: From 2016 to 2019, patients with abnormal manometry and suspected achalasia underwent esophagogastroduodenoscopy and EUS mapping of esophageal round muscle layer thickness. Maximum round layer thickness and length of round muscle layer thickness > 1.8 mm were collected and compared between opioid users and non-opioid users using Wilcoxon Rank sum test. RESULTS: 45 patients were included: 12 opioid users, 33 non-opioid users. Mean age 56.8 years (range 24-93), 53.3% male patients. Mean BMI in the opioid-induced achalasia group was 30.2 kg/m2, mean BMI in the primary achalasia group 26.8 kg/m2 (p = 0.11). In comparing endoscopic maximum round layer thickness between groups, non-opioid patients had a thicker round muscle layer (2.7 mm vs 1.8 mm, p = 0.05). Length of abnormally thickened esophageal muscle (greater than 1.8 mm) also differed between the two groups; patients on opioids had a shorter length of thickening (4.0 cm vs 0.0 cm, p = 0.04). Intervention rate was higher in the non-opioid group (p = 0.79). Of the patients that underwent therapeutic intervention, symptom resolution was higher in the non-opioid group (p = 0.002), while re-intervention post-procedure for persistent symptomatology was elevated in the opioid subset (p = 0.06). Patients in the opioid group were less likely to undergo invasive treatment (Heller). As of 2017 all interventions in the opioid group have been endoscopic. CONCLUSION: Endoscopic ultrasound is an essential tool that has improved our treatment algorithm for suspected achalasia in patients with chronic opioid usage. Incorporation of EUS findings into treatment approach may prevent unnecessary surgery in opioid users.

Protocol of early lumen apposing metal stent removal for pseudocysts and walled off necrosis avoids bleeding complications.

Background: EUS-guided drainage of pancreatic fluid collections (PFCs; pancreatic pseudocyst (PPC) or walled-off necrosis (WON)) using lumen apposing metal stents (LAMSs) is now standard of care. We adopted a protocol of early LAMS removal and prospectively followed patients to determine if this protocol avoids bleeding complications.Methods: Prospective, consecutive case series of all patients with PPC and WON who underwent drainage with LAMS at a tertiary care referral center from July 2016 to November 2018. LAMS was removed within 4 weeks for PPC and within 6 weeks for WON. Patients with residual necrosis after 6 weeks underwent removal of initial LAMS and replacement with new LAMS every 6 weeks until resolution. Patients were followed within protocol while monitoring for bleeding complications and clinical success. We also performed a literature review to determine rates of LAMS related bleeding at various timepoints.Results: Forty patients (PPC n = 19, WON n = 21) underwent drainage with LAMS. Median time for LAMS removal was 21.0 days for PPC and 33.5 days for WON. Technical success and clinical success were achieved in 40/40 patients with zero cases of delayed bleeding. A literature review of 21 studies and 1378 patients showed 52/1378 (3.8%) bleeding events with 24/52 (46.2%) events occurring within 1 week of LAMS placement.Conclusions: An early removal LAMS protocol for PFC is highly efficacious and prevents delayed bleeding. Based on analysis of published cases, half of LAMS related bleeding occurs within the first week suggesting procedural factors rather than stent dwell time impact risk of bleeding.

Low Rates of Malignancy and Mortality in Asymptomatic Patients With Suspected Neoplastic Pancreatic Cysts Beyond 5 Years of Surveillance.

BACKGROUND & AIMS: The 2015 American Gastroenterological Association guidelines recommend discontinuation of surveillance of pancreatic cysts after 5 years, although there are limited data to support this recommendation. We aimed to determine the rate of pancreatic cancer development from neoplastic pancreatic cysts after 5 years of surveillance. METHODS: We performed a retrospective multicenter study, collecting data from 310 patients with asymptomatic suspected neoplastic pancreatic cysts, identified by endoscopic ultrasound from January 2002 to June 2010 at 4 medical centers in California. All patients were followed up for 5 years or more (median, 87 mo; range, 60-189 mo). Data were used to calculate the risk for pancreatic cancer and all-cause mortality. RESULTS: Three patients (1%) developed invasive pancreatic adenocarcinoma. Based on American Gastroenterological Association high-risk features (cyst size > 3 cm, dilated pancreatic duct, mural nodule), risks for cancer were 0%, 1%, and 15% for patients with 0, 1, or 2 high-risk features, respectively. Mortality from nonpancreatic causes was 8-fold higher than mortality from pancreatic cancer after more than 5 years of surveillance. CONCLUSIONS: There is a very low risk of malignant transformation of asymptomatic neoplastic pancreatic cysts after 5 years. Patients with pancreatic lesions and 0 or 1 high-risk feature have a less than 1% risk of developing pancreatic cancer, therefore discontinuation of surveillance can be considered for select patients. Patients with neoplastic pancreatic cysts with 2 high-risk features have a 15% risk of subsequent pancreatic cancer, therefore surgery or continued surveillance should be considered.

Pancreatic cysts suspected to be branch duct intraductal papillary mucinous neoplasm without concerning features have low risk for development of pancreatic cancer.

BACKGROUND: The risk of developing pancreatic cancer is uncertain in patients with clinically suspected branch duct intraductal papillary mucinous neoplasm (BD-IPMN) based on the "high-risk stigmata" or "worrisome features" criteria proposed in the 2012 international consensus guidelines ("Fukuoka criteria"). METHODS: Retrospective case series involving patients referred for endoscopic ultrasound (EUS) of indeterminate pancreatic cysts with clinical and EUS features consistent with BD-IPMN. Rates of pancreatic cancer occurring at any location in the pancreas were compared between groups of patients with one or more Fukuoka criteria ("Highest-Risk Group", HRG) and those without these criteria ("Lowest-Risk Group", LRG). RESULTS: After exclusions, 661 patients comprised the final cohort (250 HRG and 411 LRG patients), 62% female with an average age of 67 years and 4 years of follow up. Pancreatic cancer, primarily adenocarcinoma, occurred in 60 patients (59 HRG, 1 LRG). Prevalent cancers diagnosed during EUS, immediate surgery, or first year of follow up were found in 48/661 (7.3%) of cohort and exclusively in HRG (33/77, 42.3%). Using Kaplan-Meier method, the cumulative incidence of cancer at 7 years was 28% in HRG and 1.2% in LRG patients (P<0.001). CONCLUSIONS: This study supports using Fukuoka criteria to stratify the immediate and long-term risks of pancreatic cancer in presumptive BD-IPMN. The risk of pancreatic cancer was highest during the first year and occurred exclusively in those with "high-risk stigmata" or "worrisome features" criteria. After the first year all BD-IPMN continued to have a low but persistent cancer risk.

Low yield of routine duodenal biopsies for evaluation of abdominal pain.

AIM: To determine the yield of biopsying normal duodenal mucosa for investigation of abdominal pain. METHODS: This is a retrospective chart review of consecutive patients who underwent esophagogastroduodenoscopy (EGD) with duodenal biopsies of normal appearing duodenal mucosa for an indication that included abdominal pain. All the patients in this study were identified from an electronic endoscopy database at a single academic medical center and had an EGD with duodenal biopsies performed over a 4-year period. New diagnoses that were made as a direct result of duodenal biopsies were identified. All duodenal pathology reports and endoscopy records were reviewed for indications to perform the examination as well as the findings; all the medical records were reviewed. Exclusion criteria included age less than 18 years, duodenal mass, nodule, or polyp, endoscopic duodenitis, duodenal scalloping, known celiac disease, positive celiac serology, Crohns disease, or history of bone marrow transplant. Information was collected in a de-identified database with pertinent demographic information including human immunodeficiency virus (HIV) status, and descriptive statistics were performed. RESULTS: About 300 patients underwent EGD with biopsies of benign appearing or normal appearing duodenal mucosa. The mean age of patients was 44.1 ± 16.8 years; 189 of 300 (63%) were female. A mean of 4.3 duodenal biopsies were performed in each patient. In the subgroup of patients with abdominal pain without anemia, diarrhea, or weight loss the mean age was 43.4 ± 16.3 years. Duodenal biopsies performed for an indication that included abdominal pain resulting in 4 new diagnoses (3 celiac disease and 1 giardiasis) for an overall yield of 1.3%. 183 patients with abdominal pain without anemia, diarrhea, or weight loss (out of the total 300 patients) underwent duodenal biopsy of duodenal mucosa resulting in three new diagnoses (two cases of celiac disease and one giardiasis) for a yield of 1.6%. Duodenal biopsies of 19 HIV patients presenting for evaluation of abdominal pain did not reveal any new diagnoses. Information pertaining to new diagnoses is provided. CONCLUSION: Routine biopsy of normal appearing duodena in patients with abdominal pain should be reserved for those with a high pre-test probability given its low diagnostic yield.

Rapid Growth Rates of Suspected Pancreatic Cyst Branch Duct Intraductal Papillary Mucinous Neoplasms Predict Malignancy.

BACKGROUND: The majority of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) are recommended for surveillance imaging based on consensus guidelines. However, growth rates that should prompt concern for malignant transformation of BD-IPMN are unknown. AIMS: To determine whether BD-IPMN growth can predict an increased risk of malignancy and define growth rates concerning for malignant BD-IPMN. METHODS: The study is a retrospective, multicenter study of suspected BD-IPMN patients undergoing imaging surveillance. All patients underwent EUS evaluation followed by surveillance imaging. RESULTS: Two hundred and eighty-four patients with suspected BD-IPMN without worrisome features or high-risk stigmata were followed for a median 56 months and underwent a median of four imaging studies. Nine patients (3.2 %) developed malignant BD-IPMN. Malignant BD-IPMN grew at a faster rate (18.6 vs. 0.8 mm/year; P = 0.05) compared to benign BD-IPMN. BD-IPMN growth rate between 2 and 5 mm/year was associated with an increased risk of malignancy with hazard ratio (HR) of 11.4 (95 % CI 2.2-58.6) when compared to subjects with BD-IPMN growth rate <2 mm/year (P = 0.004). BD-IPMN growth rate ≥5 mm/year had a hazard ratio of 19.5 (95 % CI 2.4-157.8) (P = 0.005). BD-IPMN growth rate of 2 mm/year had a sensitivity of 78 %, specificity of 90 %, and accuracy of 88 % to identify malignancy. Total BD-IPMN growth was also associated with increased risk of malignancy (P = 0.003) with all malignant IPMNs growing at least 10 mm prior to cancer diagnosis. CONCLUSIONS: BD-IPMN growth rates ≥2 mm/year and total growth of ≥10 mm should be considered worrisome features for BD-IPMN at increased risk of malignancy.

A long and distant journey: a case of rectal cancer with metastasis to the orbit.

We present the case of a 33-year-old man with acute onset of eye pain and diplopia as the presenting symptoms of rectal cancer with orbital metastasis. Colorectal cancer with orbital metastasis is exceedingly rare with only 7 cases worldwide despite the prevalence of colorectal cancer. The rarity of this presentation may be related to the long path through multiple vascular beds that tumor emboli from the rectum must travel in order to reach the orbit.

Enteral stenting for gastric outlet obstruction and afferent limb syndrome following pancreaticoduodenectomy.

BACKGROUND: Obstruction of the afferent or efferent limbs of a gastrojejunal anastomosis is a potential complication after pancreaticoduodenectomy (PD) resulting in either gastric outlet obstruction or afferent limb syndrome. The use of self-expanding metal stents for the management of anastomotic strictures after resection of pancreatic cancer has not been well studied. We present four such cases and review published data regarding this population. METHODS: Retrospective chart review and literature search. Outcomes were summarized with descriptive statistics. RESULTS: At our institution, 4 patients underwent metal stent placement for gastrojejunal obstruction after PD for pancreatic cancer. Enteral stents were placed in two patients across the afferent limb, in one patient across the efferent limb, and in another patient across both limbs. Similar cases in the literature revealed that the anastomotic stricture was malignant in 26 of 27 cases. Clinical improvement occurred in 88%. Afferent limb syndrome was successfully treated in 5 of 6 cases. Median survival was 3.5 months after stent placement. CONCLUSIONS: Effective palliation of both gastric outlet obstruction and afferent limb syndrome after PD can be provided with enteral stenting. Gastrojejunal strictures after PD for pancreatic cancer are usually malignant with median survival of 3.5 months after stent placement.

Malignant cell contamination may lead to false-positive findings at endosonographic fine needle aspiration for tumor staging.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of lymph nodes is used for staging of gastrointestinal malignancies. False-positive rates of 5 % - 7 % are not well understood. Elements of EUS examinations that contribute to false-positive cytological findings were investigated. PATIENTS AND METHODS: 13 patients undergoing EUS staging of gastrointestinal luminal malignancy were consecutively enrolled together with 3 patients with extraluminal tumors (pancreas, lung) defined as controls. After EUS, cellular debris and fluid were collected from the FNA needle catheter, instrument channel, and endoscope tip for cytologic and histologic investigation. RESULTS: 6 of 13 patients (46 %) had malignant cells contaminating the FNA needle catheter, instrument channel, or endoscope tip. Malignant cells were present in the instrument channel in 5 cases (38 %), exterior tip of echoendoscope in 4 (31 %) and needle catheter in 2 (15 %). CONCLUSIONS: Echoendoscopes used for FNA in patients with luminal tumors are at risk for malignant cell contamination of the instrument channel, FNA needle catheter, and echoendoscope tip. FNA needle contamination can contribute to false-positive findings.

Pseudoporphyria associated with voriconazole.

Pseudoporphyria is a rare photosensitivity that resembles porphyria cutanea tarda clinically but lacks the biochemical derangements in porphyrin metabolism. The majority of cases are induced by ingestion of particular medications. We report a case of pseudoporphyria induced by voriconazole, a second-generation triazole antifungal agent, in a lung transplant recipient. Voriconazole was not discontinued due to medical necessity. The patient's pseudoporphyria was adequately controlled with UVA and UVB protection sunscreen despite continued mild sun exposure.

Interactions between iron deficiency and lead poisoning: epidemiology and pathogenesis.

Iron deficiency and lead poisoning are common among infants and children in many parts of the world, and often these two problems are associated. Both conditions are known to cause anemia and appear to produce a more severe form of anemia when in combination. Although the nature of their relationship is not completely elucidated, characterization of a common iron-lead transporter and epidemiological studies among children strongly suggest that iron deficiency may increase susceptibility to lead poisoning. Recent human studies suggest that high iron intake and sufficient iron stores may reduce the risk of lead poisoning. Future clinical trials are necessary to assess the effect of iron supplementation in the public health prevention of lead poisoning and the kinetics of lead in the body.