Effect of the number of passes on diagnostic performance of EUS-fine needle biopsy of solid pancreatic masses: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The optimal number of passes to maximize the diagnostic ability of endoscopic ultrasound fine needle biopsy (EUS-FNB) of solid pancreatic masses (SPMs) is not well known. We conducted a systematic review to evaluate the impact of the incremental number of passes on diagnostic accuracy, tissue adequacy, and diagnostic yield for EUS-FNB of SPMs. METHODS: We searched MEDLINE, EMBASE, Scopus, and Cochrane Central for randomized controlled trials (RCTs) comparing per-pass diagnostic outcomes of FNB needles in patients with SPMs. Meta-analysis was conducted using random effects models. A separate analysis was performed on studies that used contemporary Franseen and fork-tip needles. RESULTS: Overall, 19 RCTs (N=3,552) were identified. For EUS-FNB of SPMs, three passes with any FNB needle outperformed two passes for accuracy (OR=1.58; 95%CI 1.20-2.09; I2=0%), adequacy (OR=1.97; 95%CI 1.30-2.83; I2=61%) and yield (OR=2.12; 95%CI 1.37-3.27; I2 14%). Adding a fourth or fifth pass resulted in no significant improvement in diagnostic parameters. When using contemporary FNB needles, adding a second to a single pass significantly improved accuracy (OR=1.80; 95%CI 1.23-2.63; I2=0%), adequacy (OR=2.19; 95% CI 1.65-2.90; I2=0%) and yield (OR=2.72; 95%CI 1.50-4.95; I2=0%). Adding a third pass to a second pass with contemporary needles improved adequacy (OR=2.96; 95%CI 1.97-4.46; I2=0%) but did not provide better diagnostic accuracy or yield. CONCLUSION: Two passes with Franseen or Fork-tip needles and three passes with any FNB needle suffice to provide optimal diagnostic performance for EUS-FNB of SPMs, without additional diagnostic benefits with more passes. Our results can inform future guidelines and quality benchmarks.

EUS-guided Gastroenterostomy: A Multicenter International Study Comparing Benign and Malignant Diseases.

BACKGROUND: Endoscopic ultrasound (EUS)-guided gastroenterostomy (EUS-GE) is a minimally invasive therapy for patients with gastric outlet obstruction without the risks of surgical bypass and the limited long-term efficacy of enteral self-expanding metal stent placement. However, due to its novelty, there is a lack of significant data comparing long-term outcomes of patients with EUS-GE, based on the underlying disease. In this study, we compare outcomes of EUS-GE on benign versus malignant indications. METHODS: Consecutive patients from 12 international, tertiary care centers who underwent EUS-GE over 3 years were extracted in a retrospective registry. Demographic characteristics, procedure-related information and follow-up data was collected. Primary outcome was the rate of adverse events associated with EUS-GE and the comparison of the rate of adverse events in benign versus malignant diseases. Secondary outcomes included technical and clinical success as well as hospitalization admission. RESULTS: A total of 103 patients were included: 72 malignant and 31 benign. The characteristics of the patients undergoing EUS-GE is shown in Table 1. The mean age of the cohort was 68 years and 58 years for malignant and benign etiology. Gender distribution was 57% and 39% being females in malignant and benign etiology group, respectively. Clinical success, technical success, average procedure time, and hospital length of stay were similar in both groups. Patients with benign underlying etiology had significantly higher number of surgically altered midgut anatomy (P=0.0379). CONCLUSION: EUS-GE is equally efficient regardless of the underlying etiology (malignant vs. benign), and the adverse events both groups were comparable.

Fine Needle Biopsies of Solid Pancreatic Lesions: Tissue Acquisition Technique and Needle Design Do Not Impact Specimen Adequacy.

BACKGROUND AND AIMS: Data on adequacy of EUS guided biopsies using different tissue acquisition techniques and fine needle aspiration needle designs have been inconclusive. Data on newer fine needle biopsy (FNB) needles are scarce. This study compared the performance of 3 acquisition techniques and 2 fine needle biopsy designs in solid pancreatic lesions. METHODS: Single-center, randomized, pilot clinical trial (Trial registration number NCT03264092). Patients undergoing EUS biopsy of pancreatic lesions were randomized to 1 of 3 acquisition techniques (dry suction, wet suction, slow pull) and 1 of 2 22G FNB needle designs. The primary outcome was specimen cellularity. Secondary outcomes included blood contamination and number of passes needed for diagnosis. RESULTS: A total of 52 (35.3%), 49 (33.3%) and 46 (31.3%) specimens were obtained with slow pull, dry suction and wet suction, respectively. A total of 56 (38%) and 91 (62%) specimens were obtained with each needle, respectively. No difference in cellularity scores was identified by technique (3.28 vs 3.55 vs 2.94; p = 0.081) or needle type (3.45 vs 3.15; p = 0.19). The same was true for blood contamination and diagnostic pass. A diagnosis was reached after 3 passes in 51 patients (93%). Histological diagnosis was possible in 45 specimens (82%). No severe adverse events occurred. CONCLUSIONS: Cellularity of pancreatic specimens obtained with FNB needles via EUS was not influenced by technique and needle design. Three passes were enough to obtain a histological diagnosis in most patients. Larger clinical trials are required to validate the results of this study.

Segmental Withdrawal During Screening Colonoscopy Does Not Increase Adenoma Detection Rate.

OBJECTIVES: The aim of this study was to compare a standard versus segmental withdrawal during screening colonoscopy and its effect on the adenoma detection rate (ADR). METHODS: We performed a single-center clinical trial of average-risk patients 50 years of age and older undergoing screening colonoscopy. Patients were randomized into four groups: a standard withdrawal of at least 6 or 8 minutes and a segmental withdrawal, in which ≥3 or ≥4 minutes were dedicated to the right side of the colon, with a minimum withdrawal time of at least 6 or 8 minutes, respectively. RESULTS: There were 311 patients in the study. There was no difference in ADR between the standard and segmental groups (relative ratio [RR] 0.91, P = 0.50), even after stratifying for right-sided adenomas. During standard withdrawal, an increased continuous withdrawal time was associated with a higher ADR (RR 1.08, P <0.001) and total adenomas per patient (RR 1.12, P < 0.001). A binary analysis of ≥8 minutes or <8 minutes withdrawal was associated with an increased adenomas per colonoscopy (RR 1.86, P = 0.04). These differences were not observed in the segmental group. CONCLUSIONS: Overall, there was no benefit from a segmental withdrawal protocol on ADR, but this may have been the result of the inherent limitations in the study design. After sensitivity analysis, a segmental withdrawal protocol led to an improvement in the detection of adenomas per colonoscopy and polyps per colonoscopy. A larger sample size is needed to confirm these findings.

Hispanic Americans and Non-Hispanic White Americans Have a Similar Inflammatory Bowel Disease Phenotype: A Systematic Review with Meta-Analysis.

BACKGROUND: Inflammatory bowel disease (IBD) is a devastating immune-mediated disease on the rise in Hispanics living in the USA. Prior observational studies comparing IBD characteristics between Hispanics and non-Hispanic whites (NHW) have yielded mixed results. AIMS: We performed a meta-analysis of observational studies examining IBD phenotype in Hispanics compared to NHW. METHODS: We conducted a systematic search of US-based studies comparing IBD subtype (Ulcerative Colitis: UC or Crohn's disease: CD) and phenotype (disease location and behavior) between Hispanics and NHW. We evaluated differences in age at IBD diagnosis, the presence of family history and smoking history. A random effects model was chosen "a priori." Categorical and continuous variables were analyzed using odds ratio (OR) or standard mean difference (SMD), respectively. RESULTS: Seven studies were included with 687 Hispanics and 1586 NHW. UC was more common in Hispanics compared to NHW (OR 2.07, CI 1.13-3.79, p = 0.02). Location of disease was similar between Hispanics and NHW except for the presence of upper gastrointestinal CD, which was less common in Hispanics (OR 0.58, CI 0.32-1.06, p = 0.07). Hispanics were less likely to smoke (OR 0.48, CI 0.26-0.89, p = 0.02) or have a family history of IBD (OR 0.35, CI 0.22-0.55, p < 0.001). CD behavior classified by Montreal classification and age at IBD diagnosis were similar between Hispanics and NHW. CONCLUSION: UC was more common among US Hispanics compared to NHW. Age at IBD diagnosis is similar for both Hispanics and NHW. For CD, disease behavior is similar, but Hispanics show a trend for less upper gastrointestinal involvement. A family history of IBD and smoking history were less common in Hispanics.

The human jejunum has an endogenous microbiota that differs from those in the oral cavity and colon.

BACKGROUND: The upper half of the human small intestine, known as the jejunum, is the primary site for absorption of nutrient-derived carbohydrates, amino acids, small peptides, and vitamins. In contrast to the colon, which contains 1011-1012 colony forming units of bacteria per ml (CFU/ml), the normal jejunum generally ranges from 103 to 105 CFU per ml. Because invasive procedures are required to access the jejunum, much less is known about its bacterial microbiota. Bacteria inhabiting the jejunal lumen have been investigated by classical culture techniques, but not by culture-independent metagenomics. RESULTS: The lumen of the upper jejunum was sampled during enteroscopy of 20 research subjects. Culture on aerobic and anaerobic media gave live bacterial counts ranging from 5.8 × 103 CFU/ml to 8.0 × 106 CFU/ml. DNA from the same samples was analyzed by 16S rRNA gene-specific quantitative PCR, yielding values from 1.5 × 105 to 3.1 × 107 bacterial genomes per ml. When calculated for each sample, estimated bacterial viability ranged from effectively 100% to a low of 0.3%. 16S rRNA metagenomic analysis of uncultured bacteria by Illumina MiSeq sequencing gave detailed microbial composition by phylum, genus and species. The genera Streptococcus, Prevotella, Veillonella and Fusobacterium, were especially abundant, as well as non-oral genera including Escherichia, Klebsiella, and Citrobacter. The jejunum was devoid of the genera Alistipes, Ruminococcus, Faecalibacterium, and other extreme anaerobes abundant in the colon. In patients with higher bacterial loads, there was no significant change in microbial species composition. CONCLUSIONS: The jejunal lumen contains a distinctive bacterial population consisting primarily of facultative anaerobes and oxygen-tolerant obligate anaerobes similar to those found in the oral cavity. However, the frequent abundance of Enterobacteriaceae represents a major difference from oral microbiota. Although a few genera are shared with the colon, we found no evidence for retrograde movement of the most abundant colonic microbes to the jejunum. Some individuals had much higher bacterial loads, but this was not correlated with decreases in bacterial species diversity or other evidence of dysbiosis.

Demographic and Clinical Characteristics of a Predominantly Hispanic Population with Inflammatory Bowel Disease on the US-Mexico Border.

OBJECTIVES: Information regarding Hispanics with inflammatory bowel disease (IBD) is scarce. In this study we aimed to describe a predominantly Hispanic population with IBD in a city located along the US-Mexico border and to identify clinical or demographic differences between Hispanics and non-Hispanics. METHODS: Retrospective cohort analysis of patients with IBD between 2003 and 2013 at a tertiary care center. Information collected included age, sex, ethnicity, diagnosis, diagnosis status (new vs old), endoscopic extent of disease (EOD), extraintestinal manifestations, medical treatment, and surgeries performed. Continuous and categorical variables were compared using a two-sided unpaired t test/Wilcoxon rank sum test and the Fisher exact test, respectively. Results with P ≤ 5% were considered statistically significant. RESULTS: Hispanics accounted for 71% of the population sample. A total of 141 patients (68%) were diagnosed as having ulcerative colitis (UC) and 67 (32%) as having Crohn disease (CD). The only statistically significant differences between Hispanics and non-Hispanics were older age at diagnosis and a higher proportion of new diagnoses in Hispanics with CD (P = 0.008 and 0.009, respectively) The most common EOD in patients with UC was extensive colitis, whereas isolated colonic disease predominated in CD, regardless of ethnicity. Immunomodulators and biologics were used in 3% and 1% of cases, respectively. Treatment regimens were similar in both ethnic groups. Patients with CD were more likely than those with UC to have undergone surgery (27% vs 11%, P = 0.004). Surgery rates did not differ between Hispanics and non-Hispanics. CONCLUSIONS: In our population, UC was more common than CD, and the EOD of both conditions differed from the one previously described in other Hispanic populations in the United States. The use of immunomodulators and biologics is the lowest reported to date in the country. No clinically relevant differences were seen between Hispanics and non-Hispanics.

Endoscopic Ultrasound-Guided Cholecystoenterostomy for Acute Hemorrhagic Cholecystitis Drainage.

Hemorrhagic cholecystitis is a rare entity with few cases reported in the literature. We report a case of a 42-year-old man with cirrhosis who presented to the hospital with abdominal pain in the right upper quadrant radiating to the back. Computed tomography scan showed findings consistent with acute cholecystitis. Owing to decompensated cirrhosis, he was not a good candidate for cholecystectomy. Endoscopic ultrasound-guided cholecystoenterostomy was performed that immediately yielded a large amount of old blood with clots along with some bile consistent with acute hemorrhagic cholecystitis. After the drainage, he had an uneventful hospitalization.

Response of Locally Advanced Pancreatic Cancer to Intratumoral Injection of Large Surface Area Microparticle Paclitaxel: Initial Report of Safety and Clinical Outcome.

OBJECTIVES: Large surface area microparticle paclitaxel (LSAM-PTX) provides an intratumoral (IT) chemotherapeutic depot. Safety, tolerability, and tumor response to IT LSAM-PTX delivered by endoscopic ultrasound-fine needle injection were evaluated in subjects with unresectable locally advanced pancreatic cancer (LAPC). METHODS: Ten subjects treated in a dose escalation phase and 22 additional subjects receiving 2 injections, 4 weeks apart, of 15 mg/mL LSAM-PTX were followed for 12 months. Paclitaxel pharmacokinetics were evaluated, imaging at 3 and 6 months determined tumor response, and multiplex immunofluorescence was conducted to characterize local immune response. RESULTS: Most treatment-emergent adverse events were attributed to LAPC. Plasma paclitaxel levels were negligible. Eight subjects' tumors became resectable after IT LSAM-PTX, and 5 of 6 (83%) were resected with R0. Multiplex immunofluorescence of resected tumors demonstrated increased T cells, natural killer cells, and macrophages and decreased myeloid-derived suppressor cells. Six-month disease control rate was 94%, and median overall survival was 19.7 months in the 2-injection subjects. For nonresected and resected groups, overall survival times were 18.9 and 35.2 months, respectively. CONCLUSIONS: Neoadjuvant IT LSAM-PTX, in combination with SOC, was well tolerated and may provide benefits to LAPC patients, evidenced by enhanced immune response, improved disease control rate, restaging leading to surgery, and extended survival.

Pancreatic Neuroendocrine Tumors: The Effect of Facility Type on Patient Survival.

OBJECTIVES: During the last decades, significant progress has been made in the management of patients with pancreatic neuroendocrine tumors (pNETs). It is unclear how the type of the treating health care facility alters patient outcomes. METHODS: Data from pNETs reported to the National Cancer Database between 2004 and 2016 were examined. Types of institutions were as follows: academic/research cancer program (ARP), comprehensive community cancer program (CCCP), integrated network cancer program (INCP), and community cancer program (CCP). RESULTS: A total of 17,887 patients with pNETs were analyzed. Treatment at ARPs was significantly associated with receipt of surgery (ARP, 61.9%; CCCP, 45.6%; CCP, 29.9%; INCP, 55.5%; P < 0.001), both for patients with very early tumors ≤2 cm (ARP, 74.7%; CCCP, 66.5%; CCP, 52.4%; INCP, 71.6%; P < 0.001) and for patients with liver metastases (ARP, 21.3%; CCCP, 10.6%; CCP, 5%; INCP, 16.8%; P < 0.001). Treatment at ARPs was associated with improved survival (median overall survival: ARP, 91 mo; CCCP, 47 mo; CCP, 24.5 mo; INCP, 72 mo; P < 0.001). CONCLUSIONS: Treatment of pNETs at academic/research programs is associated with more frequent resections and best survival outcomes. This survival benefit exists for early and late stages and after adjusting for known cofactors.

Early phase trial of intracystic injection of large surface area microparticle paclitaxel for treatment of mucinous pancreatic cysts.

Background and study aims Mucinous pancreatic cystic lesions (PCLs) have the potential for malignant transformation, for which the only accepted curative modality is surgery. A novel intracystic therapy with large surface area microparticle paclitaxel (LSAM-PTX) may treat PCLs without local or systemic toxicities. Safety and preliminary efficacy of LSAM-PTX for the treatment of PCLs administered by endoscopic ultrasound-guided fine-needle injection (EUS-FNI) was evaluated. Patients and methods Ten subjects with confirmed PCLs (size > 1.5 cm) received intracystic LSAM-PTX via EUS-FNI at volumes equal to those aspirated from the cyst in sequential cohorts at 6, 10, and 15 mg/mL in a standard "3 + 3" dose-escalation protocol. The highest dose with acceptable safety and tolerability was taken into the confirmatory phase where nine additional subjects received two injections of LSAM-PTX 12 weeks apart. Subjects were followed for 6 months after initial LSAM-PTX treatment for endpoints including: adverse events (AEs), tolerability, pharmacokinetic analysis of systemic paclitaxel drug levels, and change in cyst volume. Results Nineteen subjects completed the study. No dose-limiting toxicities, treatment-related serious AEs, or clinically significant laboratory changes were reported. Systemic paclitaxel concentrations did not exceed 3.5 ng/mL at any timepoint measured and fell below 1 ng/mL by Week 2, supporting the lack of systemic toxicity. By Week 24 a cyst volume reduction (10-78 %) was seen in 70.6 % of subjects. Conclusions Intracystic injection of LSAM-PTX into mucinous PCLs resulted in no significant AEs, a lack of systemic absorption, and resulted in reduction of cyst volume over a 6 month period.

Endoscopic Treatment of Esophageal Varices.

Acute variceal bleeding is a complication of portal hypertension, usually due to cirrhosis, with high morbidity and mortality. There are 3 scenarios for endoscopic treatment of esophageal varices: prevention of first variceal bleed, treatment of active variceal bleed, and prevention of rebleeding. Patients with cirrhosis should be screened for esophageal varices. Recommended endoscopic therapy for acute variceal bleeding is endoscopic variceal banding. Although banding is the first-choice treatment, sclerotherapy may have a role. Treatment with Sengstaken-Blakemore tube or self-expanding covered metallic esophageal stent can be used for acute variceal bleeding refractory to standard pharmacologic and endoscopic therapy.

Acquired thrombotic thrombocytopenic purpura: puzzles, curiosities and conundrums.

We report a case of acquired thrombotic thrombocytopenic purpura (TTP) in a 34-year old patient with a prior diagnosis of systemic lupus erythematosis (SLE) who was recently started on hydroxychloroquine. Presenting symptoms included fevers, sore throat and productive cough with progressive weakness, dyspnea on exertion, hemoptysis and dark urine. Initial laboratory abnormalities were consistent with an acute microangiopathic hemolytic anemia and severe thrombocytopenia. At the time of admission, the patient's lupus was highly active as evident by his high SLE Disease Activity Index (SLEDAI) score. He was later also found to have severely reduced ADAMTS-13 levels and a positive antibody assay. This case highlights the occasional difficulty in pinpointing the exact etiology of TTP as well as establishes a possible novel drug association between hydroxychloroquine and TTP development.

Artificial intelligence for early detection of pancreatic adenocarcinoma: The future is promising.

Pancreatic ductal adenocarcinoma (PDAC) is a worldwide public health concern. Despite extensive research efforts toward improving diagnosis and treatment, the 5-year survival rate at best is approximately 15%. This dismal figure can be attributed to a variety of factors including lack of adequate screening methods, late symptom onset, and treatment resistance. Pancreatic ductal adenocarcinoma remains a grim diagnosis with a high mortality rate and a significant psy-chological burden for patients and their families. In recent years artificial intelligence (AI) has permeated the medical field at an accelerated pace, bringing potential new tools that carry the promise of improving diagnosis and treatment of a variety of diseases. In this review we will summarize the landscape of AI in diagnosis and treatment of PDAC.

Facility Type Affects Treatment Outcomes for Patients With Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: Academic centers report better outcomes for pancreatic ductal adenocarcinoma. We hypothesized that treatment outcomes for mucinous cysts differ according to institution type. METHODS: Using the National Cancer Data Base, we analyzed data on patients with mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs). RESULTS: Of 3278 identified patients, 2622 (80%) had IPMNs and 656 (20%) had MCNs. While most academic/research programs (ARCPs, 84.9%) treated more than 10 patients/year, this was true for only 59% of integrated network cancer programs, 37.3% of comprehensive community cancer programs, and 0% of community cancer programs (P < 0.001). Surgery was used more often in ARCPs and for smaller tumors. The ARCPs had higher rates of margin negative resections with retrieval of 15 or more nodes with the lowest 30- and 90-day mortality rates. The median overall survival was better in ARCPs (110.3 months) than comprehensive community cancer programs (75.1 mo), community cancer programs (75.1 mo), or integrated network cancer programs (100.8 mo, P < 0.001). CONCLUSIONS: Treatment of MCNs and IPMNs of the pancreas at academic centers is associated with a higher probability of pancreatectomy, disease identification in a noninvasive stage, and better overall survival. Centralization of care for mucinous pancreatic cysts will lead to improved outcomes.