Reconstruction and Simulation of Neocortical Microcircuitry.

We present a first-draft digital reconstruction of the microcircuitry of somatosensory cortex of juvenile rat. The reconstruction uses cellular and synaptic organizing principles to algorithmically reconstruct detailed anatomy and physiology from sparse experimental data. An objective anatomical method defines a neocortical volume of 0.29 ± 0.01 mm(3) containing ~31,000 neurons, and patch-clamp studies identify 55 layer-specific morphological and 207 morpho-electrical neuron subtypes. When digitally reconstructed neurons are positioned in the volume and synapse formation is restricted to biological bouton densities and numbers of synapses per connection, their overlapping arbors form ~8 million connections with ~37 million synapses. Simulations reproduce an array of in vitro and in vivo experiments without parameter tuning. Additionally, we find a spectrum of network states with a sharp transition from synchronous to asynchronous activity, modulated by physiological mechanisms. The spectrum of network states, dynamically reconfigured around this transition, supports diverse information processing strategies. PAPERCLIP: VIDEO ABSTRACT.

Assessment of large-diameter and small-diameter SoftK specialty contact lenses for early-stage keratoconus.

INTRODUCTION: Soft contact lenses may be a good alternative for early-stage keratoconus (KC) patients who do not tolerate rigid gas permeable (RGP) lenses due to ocular discomfort or complications. This prospective study compared outcomes obtained after 2 weeks of wearing two types of soft silicone hydrogel contact lenses for keratoconus that varied in their diameter and central thickness (cc). METHODS: Patients with Amsler-Krumeich grades I or II KC were fitted with small-diameter (14.2 or 14.8 mm) SoftK (SD-SoftK, cc = 0.48 mm) and large-diameter (17 mm) SoftK (LD-SoftK, cc = 0.60 mm) lenses, each worn for 2 weeks in a crossover design. Low (10%;10VA) and high (100%;100VA) contrast visual acuity, contrast sensitivity (CS, Pelli-Robson), higher order aberrations (HOAs, Visionix Vx130), the number of trial lens modifications during fitting and the subjectively preferred lens were compared using Friedman tests with post-hoc analysis. RESULTS: Forty eyes (N = 20, 10 males, mean age: 39.0 ± 9.9 years, range: 23-55 years) were examined. Their habitual median (interquartile1, interquartile3) 10VA (LogMAR), 100VA (LogMAR) and CS (LogCS) were 0.52 (0.30, 0.50), 0.14 (0.10, 0.15) and 1.35 (1.35, 1.50), respectively. For the SD-SoftK condition, the values were 0.23 (0.17, 0.30), 0.02 (0.00, 0.05) and 1.50 (1.50, 1.65), respectively. For the LD-SoftK condition, the respective values were 0.36 (0.27, 0.44), 0.09 (0.05, 0.13) and 1.50 (1.50, 1.60). SD-SoftK lenses significantly improved 10VA compared with habitual and LD-SoftK. SD-SoftK also significantly improved CS compared with habitual, but not LD-SoftK. LD-SoftK significantly improved spherical aberration compared with uncorrected (0.03 ± 0.10 µ vs. 0.07 ± 0.13 µ) but not SD-SoftK (0.04 ± 0.07 µ). Both lenses required a mean of 1.5 modifications prior to final lens fitting. Fewer adverse events were seen with SD-SoftK (N = 3) compared with LD-SoftK (N = 8), and 75% of participants preferred SD-SoftK lenses. CONCLUSION: SD-SoftK lenses were preferred by 75% of subjects, were associated with fewer adverse events and significantly improved 10VA compared with LD-SoftK lenses. SD-SoftK lenses also significantly improved CS compared with the habitual correction, but this did not differ significantly from the LD-SoftK lenses.

A retinoscopic survey of donkeys and goats.

PURPOSE: Assess the refractive states of donkeys and goats. METHODS: Forty-two donkeys and 28 goats were enrolled. The mean ± SD ages were 7.68 ± 7.33 years for donkeys and 4.26 ± 2.33 years for goats. Seven donkeys and one goat were <6 months old. Retinoscopy was performed in alert animals, following cycloplegia in goats but not in donkeys. Normality was determined using the Kolmogorov-Smirnov test. The two primary meridians and two eyes were compared using Pearson's correlation and paired Student's t-tests. The association between refractive states and age was examined using one-way ANOVA in donkeys and a paired Student's t-test in goats. One-sample t-tests were conducted to assess if the refractive error distributions were significantly different from "0". RESULTS: The mean ± SD spherical equivalent (SE) refractive errors of the right and left donkey eyes were -0.80 ± 1.03 D and -0.35 ± 0.95 D, respectively. The majority (86%) of the donkeys had an astigmatic refraction and eight (19%) had anisometropia. The mean SE refractive errors of the right and left goat eyes were -0.15 ± 1.1 D and -0.18 ± 1.2 D, respectively. The majority (54%) of the goat eyes had an astigmatic refraction and five (18%) had anisometropia. The right and left eye SE refractive errors were positively correlated in both species (both p = .9). Age was not correlated with refractive error in both donkeys (p = .09) and goats (p = .6). CONCLUSIONS: Both goats and donkeys are emmetropic.

Capsule Endoscopy Crohn's Disease Activity Index (CECDAIic or Niv Score) for the Small Bowel and Colon.

BACKGROUND AND THE STUDY AIM: Crohn's disease (CD) is a chronic inflammatory disorder defined as a transmural inflammation of the bowel wall, affecting the small and large intestine. The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity. We extended the Niv score to the colon and have a comprehensive view of the whole intestine. METHODS: We evaluated 3 parameters of intestinal pathology: A, Inflammation; B, Extent of disease; C, Presence of strictures. The scoring formula is as follows: CEDCAIic=(A1×B1+C1)+(A2×B2+C2)+(A3×B3+C3)+(A4×B4+C4) (1=proximal small bowel, 2=distal small bowel, 3=right colon, 4=left colon). RESULTS: The median CECDAIic score was 15.5 (range, 0 to 42), and the mean±SD score was 17.2±11.5. The CECDAIic scores per patient were similar among the 5 observers. Kendall's coefficient of concordance was high and significant for almost all the parameters examined except for strictures in the proximal small bowel and distal colon. Nevertheless, the coefficients for the small bowel and for the whole intestine were high, 0.85 and 0.77, P<0.0001, respectively. CONCLUSIONS: We established a new score, the CECDAIic of the small-bowel and colonic CD. We offer this easy, user-friendly score for use in randomized controlled trials and in the clinical follow-up of CD patients.

Accuracy of capsule colonoscopy in detecting colorectal polyps in a screening population.

BACKGROUND & AIMS: Capsule colonoscopy is a minimally invasive imaging method. We measured the accuracy of this technology in detecting polyps 6 mm or larger in an average-risk screening population. METHODS: In a prospective study, asymptomatic subjects (n = 884) underwent capsule colonoscopy followed by conventional colonoscopy (the reference) several weeks later, with an endoscopist blinded to capsule results, at 10 centers in the United States and 6 centers in Israel from June 2011 through April 2012. An unblinded colonoscopy was performed on subjects found to have lesions 6 mm or larger by capsule but not conventional colonoscopy. RESULTS: Among the 884 subjects enrolled, 695 (79%) were included in the analysis of capsule performance for all polyps. There were 77 exclusions (9%) for inadequate cleansing and whole-colon capsule transit time fewer than 40 minutes, 45 exclusions (5%) before capsule ingestion, 15 exclusions (2%) after ingestion and before colonoscopy, and 15 exclusions (2%) for site termination. Capsule colonoscopy identified subjects with 1 or more polyps 6 mm or larger with 81% sensitivity (95% confidence interval [CI], 77%-84%) and 93% specificity (95% CI, 91%-95%), and polyps 10 mm or larger with 80% sensitivity (95% CI, 74%-86%) and 97% specificity (95% CI, 96%-98%). Capsule colonoscopy identified subjects with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity (95% CI, 82%-93) and 82% specificity (95% CI, 80%-83%), and 10 mm or larger with 92% sensitivity (95% CI, 82%-97%) and 95% specificity (95% CI, 94%-95%). Sessile serrated polyps and hyperplastic polyps accounted for 26% and 37%, respectively, of false-negative findings from capsule analyses. CONCLUSIONS: In an average-risk screening population, technically adequate capsule colonoscopy identified individuals with 1 or more conventional adenomas 6 mm or larger with 88% sensitivity and 82% specificity. Capsule performance seems adequate for patients who cannot undergo colonoscopy or who had incomplete colonoscopies. Additional studies are needed to improve capsule detection of serrated lesions. Clinicaltrials.gov number: NCT01372878.

Assessment of a Clinical Test for Detection of Alteration in Visual Perception Due to Astigmatism.

Purpose: Astigmatism blurs the retinal image of a circular spot along a particular orientation rendering it an elliptical shape. Astigmatic patients demonstrate adaptation to residual astigmatic blur that may affect their discrimination between oval and circular targets. The Wilkins Egg and Ball Test (WEBT) was created to detect altered visual perception due to residual astigmatic blur by discriminating a circle within a row of oval elements. This prospective, cross-sectional study examined the utility of WEBT in detecting uncorrected residual astigmatism on the perception of form symmetry in astigmatic and keratoconic participants as well as normal participants with induced astigmatism at four primary meridians. Methods: The mean search time (sT) and number of errors (noE) of 33 non-astigmatic controls (mean age: 24±5, range: 18-43, 6 males), 23 astigmatic participants (mean age: 36±12, range: 18-43, 6 males) and 13 keratoconic participants (N=22 eyes, mean age: 36±12, range: 18-58, 6 males) were measured under baseline, and 2.00 DC induced cylinder at four primary meridians, and for uncorrected, spherical-correction only, and fully corrected conditions, respectively. Mean sT and noE were converted to Z-scores, combined for each condition, and compared using repeated measures ANOVA with post-hoc analysis. Results: Combined Z-scores for the controls were significantly worse (p<0.001) for all induced cylinder conditions. The induced 180° condition was significantly better than 45° and 90° conditions (p=0.04), but not the 135° condition. For both astigmatic and keratoconic cohorts, Z-scores of the uncorrected condition were significantly worse than the fully corrected condition (both p<0.01), but the fully corrected and spherical-only conditions did not differ significantly (p=0.06 and p=0.05, respectively). Conclusion: In accommodating young adults, WEBT detected altered visual perception due to overall blur, and moderate-high amounts of uncorrected induced astigmatism and keratoconus, but is not useful as a tool for detection of altered visual perception due to small residual astigmatic blur.

The Role of Hub Neurons in Modulating Cortical Dynamics.

Many neurodegenerative diseases are associated with the death of specific neuron types in particular brain regions. What makes the death of specific neuron types particularly harmful for the integrity and dynamics of the respective network is not well understood. To start addressing this question we used the most up-to-date biologically realistic dense neocortical microcircuit (NMC) of the rodent, which has reconstructed a volume of 0.3 mm3 and containing 31,000 neurons, ∼37 million synapses, and 55 morphological cell types arranged in six cortical layers. Using modern network science tools, we identified hub neurons in the NMC, that are connected synaptically to a large number of their neighbors and systematically examined the impact of abolishing these cells. In general, the structural integrity of the network is robust to cells' attack; yet, attacking hub neurons strongly impacted the small-world topology of the network, whereas similar attacks on random neurons have a negligible effect. Such hub-specific attacks are also impactful on the network dynamics, both when the network is at its spontaneous synchronous state and when it was presented with synchronized thalamo-cortical visual-like input. We found that attacking layer 5 hub neurons is most harmful to the structural and functional integrity of the NMC. The significance of our results for understanding the role of specific neuron types and cortical layers for disease manifestation is discussed.

Impact of higher order network structure on emergent cortical activity.

Synaptic connectivity between neocortical neurons is highly structured. The network structure of synaptic connectivity includes first-order properties that can be described by pairwise statistics, such as strengths of connections between different neuron types and distance-dependent connectivity, and higher order properties, such as an abundance of cliques of all-to-all connected neurons. The relative impact of first- and higher order structure on emergent cortical network activity is unknown. Here, we compare network structure and emergent activity in two neocortical microcircuit models with different synaptic connectivity. Both models have a similar first-order structure, but only one model includes higher order structure arising from morphological diversity within neuronal types. We find that such morphological diversity leads to more heterogeneous degree distributions, increases the number of cliques, and contributes to a small-world topology. The increase in higher order network structure is accompanied by more nuanced changes in neuronal firing patterns, such as an increased dependence of pairwise correlations on the positions of neurons in cliques. Our study shows that circuit models with very similar first-order structure of synaptic connectivity can have a drastically different higher order network structure, and suggests that the higher order structure imposed by morphological diversity within neuronal types has an impact on emergent cortical activity.

Video capsule endoscopy is safe and effective in suspected small bowel bleeding among left ventricular assist device recipients.

INTRODUCTION:: Suspected small bowel bleeding is frequently encountered in left ventricular assist device recipients and the identification of the culprit lesion may be challenging. Data regarding the safety and yield of small bowel capsule in the investigation of suspected small bowel bleeding are limited. We aimed to evaluate the safety and efficacy of small bowel video capsule endoscopy for the investigation of suspected small bowel bleeding among left ventricular assist device recipients. METHODS:: Patients with left ventricular assist device who underwent video capsule endoscopy for the investigation of suspected small bowel bleeding were identified. Suspected small bowel bleeding was defined as the presence of overt bleeding at least 30 days following left ventricular assist device implantation with no identifiable cause in upper and lower endoscopy. RESULTS:: A total of 10 patients with left ventricular assist device associated suspected small bowel bleeding performed 12 small bowel capsule endoscopies between January 2008 and December 2015 at our tertiary medical care facility. There were no cases of capsule retention or any other serious adverse events during the exams. A significant finding was identified in 8 out of 10 patients, including 3 cases of small bowel angioectasia, 2 cases of small bowel ulcers, 1 case of cecal polyp, and 2 cases of active bleeding with no apparent bleeding source. Small bowel enteroscopy identified and treated bleeding angioectasia in the latter two cases. CONCLUSION:: Small bowel capsule endoscopy is safe and effective in the investigation of left ventricular assist device associated suspected small bowel bleeding.

Open access gastroscopy in hospitalized patients.

BACKGROUND: Open access gastroscopy allows physicians to refer patients for endoscopic procedures without a prior consultation. OBJECTIVES: To compare the safety and efficacy of OAG with gastroscopy performed after a gastroenterological consultation. METHODS: Patients referred for gastroscopy directly (open access) or after consultation with a gastroenterologist, by physicians in the departments of internal medicine and surgery at a major tertiary center, were compared for indications, background disease, outcome and diagnostic yield. The data were collected prospectively over a 5 month period following the introduction of OAG at the center. Physicians in both departments participated in an education program on the indications and procedure of gastroscopy. For each patient referred for OAG the attending physician completed a specially designed questionnaire that had to be signed by a senior physician. Data were managed and analyzed with Excel and SPSS software. RESULTS: The study sample comprised 494 patients, of whom 236 were referred for OAG and 258 after prior consultation. On multivariate analysis, hospitalization in the department of internal medicine was the only independent factor for OAG. Severe background disease and aspirin treatment had no effect on physician use of OAG, although they served as a "red light" for the gastroenterology consultants. There was no difference in the diagnostic yield of the procedures (26.4% normal findings for OAG and 28.3% for consultations) or in mortality rates. The main indications for referral to gastroscopy in the surgery department were melena, hematemesis and "coffee grounds," and anemia and vomiting in the internal medicine department. CONCLUSIONS: OAG is feasible and beneficial in an academic medical center setting, with no bias in appropriateness of indications or decrease in the diagnostic yield compared to the traditional approach. More attention should be directed to safety issues by the referring physicians.

Rich cell-type-specific network topology in neocortical microcircuitry.

Uncovering structural regularities and architectural topologies of cortical circuitry is vital for understanding neural computations. Recently, an experimentally constrained algorithm generated a dense network reconstruction of a ∼0.3-mm3 volume from juvenile rat somatosensory neocortex, comprising ∼31,000 cells and ∼36 million synapses. Using this reconstruction, we found a small-world topology with an average of 2.5 synapses separating any two cells and multiple cell-type-specific wiring features. Amounts of excitatory and inhibitory innervations varied across cells, yet pyramidal neurons maintained relatively constant excitation/inhibition ratios. The circuit contained highly connected hub neurons belonging to a small subset of cell types and forming an interconnected cell-type-specific rich club. Certain three-neuron motifs were overrepresented, matching recent experimental results. Cell-type-specific network properties were even more striking when synaptic strength and sign were considered in generating a functional topology. Our systematic approach enables interpretation of microconnectomics 'big data' and provides several experimentally testable predictions.

Inflammatory bowel disease: an emergent disease among Ethiopian Jews migrating to Israel.

BACKGROUND: The development and characteristics of inflammatory bowel disease (IBD) in Ethiopian Jewish immigrants to Israel were investigated. METHODS: A case-control study was conducted in 7 tertiary care hospitals in Israel. Patients of Ethiopian origin with IBD >6 months were included. Time of disease onset after immigration and age at diagnosis were recorded. Randomly chosen patients with IBD of Ashkenazi Jewish origin served as controls. Demographics and clinical parameters were compared between the 2 cohorts. RESULTS: Thirty-two Ethiopian patients with IBD were compared with 33 Ashkenazi Jewish patients with IBD. Crohn's disease (CD) was more prevalent than ulcerative colitis (UC) in the Ethiopian group compared with the Ashkenazi group (94% versus 73%, P = 0.02). No Ethiopian-origin patient had a positive family history of IBD compared with 42% of Ashkenazi-origin patients (P < 0.001). Arthritis was more common in Ashkenazi than in Ethiopian patients (27% versus 3%, P < 0.01). One Ashkenazi patient with CD had upper gastrointestinal involvement compared with 7 (23%) in the Ethiopian group (P < 0.02). All other clinical measures were similar between the 2 cohorts. The Ethiopian group lived in Israel with a mean of 13 ± 5 years, and 75% were born in Ethiopia. The shortest time between immigration and developing IBD was 8 years (range, 8-26; median 16 yrs). No Ethiopian patient was diagnosed before immigration. CONCLUSIONS: Ethiopian Jews migrating to Israel are at risk of developing IBD. Larger cohorts are needed to determine the relative importance of environmental and genetic factors that cause IBD in these patients.

Surgical clip found in duodenal ulcer after laparoscopic cholecystectomy.

The wide use of surgical clips in laparoscopic surgery has led to a variety of complications. We describe two cases in which a surgical clip was incorporated into a duodenal ulcer after laparoscopic cholecystectomy. The presenting symptom was acute gastrointestinal bleeding. Both patients were treated endoscopically, and the bleeding stopped after the clip was removed from the ulcer base. Although the mechanism by which a surgical clip migrates into the duodenum is unclear, we recommend meticulous Calot's triangle dissection and removal of any wandering or misplaced clips. Endoscopic removal is recommended when a surgical clip is discovered in a bleeding ulcer.

13C-urea breath test to validate eradication of Helicobacter pylori in an Israeli population.

BACKGROUND: The 13C-urea breath test is the best non-invasive test to validate Helicobacter pylori eradication. Serology is unreliable for this purpose due to the slow and unpredictable decline in the antibody titer. OBJECTIVES: To characterize a specific group of patients who were treated for H. pylori and tested for successful eradication by 13C-UBT in our central laboratory, to correlate the eradication success rate with specific drug combinations, and to evaluate other factors that may influence eradication success. METHODS: 13C-UBT for H. pylori was performed in the central laboratory of Clalit Health Services. The breath test was performed by dedicated nurses in 25 regional laboratories and the samples were analyzed by a mass spectrometer (Analytical Precision 2003, UK). The physician who ordered the test completed a questionnaire computing demographic data (age, gender, origin), indication, use of non-steroidal anti-inflammatory drugs or proton pump inhibitor, and combination of eradication therapy. RESULTS: Of the 1,986 patients tested to validate successful H. pylori eradication, 539 (27%) had a positive test (treatment failure group) and 1,447 (73%) had a negative test (successful treatment group). Male gender, older age and European-American origin predicted better eradication rates. Dyspeptic symptoms and chronic PPI therapy predicted treatment failure. Combination therapy that included clarithromycin had a higher eradication rate than a combination containing metronidazole. The combination of omeprazole, amoxicillin and clarithromycin achieved an eradication rate of 81.3%, which was better than the combination of omeprazole, metronidazole and clarithromycin (77.2%) (not significant), or of omeprazole, amoxicillin and metronidazole (66.1%) (P < 0.01). CONCLUSION: Gender, age, origin, dyspepsia and PPI therapy may predict H. pylori eradication results. Our findings also support an increase in metronidazole resistance of H. pylori strains in Israel, as reported in other countries. We recommend combination therapy with omeprazole, amoxicillin and clarithromycin and avoidance of metronidazole as one of the first-line eradication drugs.

Impact of colonoscopy on quality of life.

INTRODUCTION: Colonoscopy of asymptomatic, healthy individuals for colorectal cancer screening rarely causes complications and adverse events. Thus, quality of life (QOL) of the participants should not be affected by the procedure. AIM: The aim of the study was to isolate the influence of colonoscopy, by investigation QOL before and after the procedure in a cohort of consecutive patients with different indications. METHODS: This study is a prospective, longitudinal study, designed to compare the potential influence of colonoscopy on QOL. For a cohort of consecutive patients undergoing colonoscopy for various reasons and indications, we filled a QOL short form-36 and a short feedback questionnaire before, immediately after, and a month after the procedure. We also measured the quality of the endoscopy, the outcome in patients, and acceptability among patients. RESULTS: There was no significant change before and immediately after colonoscopy in any of the short form-36 parameters. Physical functioning, role limitation physical, pain, general health, vitality, social functioning, role limitation mental, and mental health had very similar scores before and 2-3 h after the procedure. There was a decrease in the physical functioning a month after the procedure (P=0.01). The same was found for non-inflammatory bowel disease patients, but not for inflammatory bowel disease patients. CONCLUSION: Colonoscopy did not affect QOL in the short or the long duration after the procedure. As such, colonoscopy may be suitable as a part of screening programs. We believe that QOL estimation should be an integral part of assessment of a screening program.

Fecal immunochemical test and small bowel lesions detected on capsule endoscopy: results of a prospective study in patients with obscure occult gastrointestinal bleeding.

BACKGROUND: Fecal immunochemical test (FIT) is gaining popularity as a screening tool for colorectal cancer. The introduction of capsule endoscopy (CE) enables an assessment of the relationship between small bowel (SB) lesions and FIT results. AIM: To determine whether SB lesions found by CE are associated with an increased rate of positive FIT. METHODS: Consecutive patients undergoing CE for obscure occult gastrointestinal bleeding also underwent FIT. CE was performed using the PillCam SB and FIT was performed with OC-Micro (three samples, threshold 75 and 100 ng/ml). RESULTS: Fifty-one patients were included; the mean lowest hemoglobin was 9.1 ± 2.1 g/dl. Twenty-six patients (51.0%) had SB lesions identified by CE and were classified as the probable or suspected source of bleeding. At the threshold of 75 and 100 ng/ml, 12 of 26 (46.1%) and 10 of 26 (38.4%), respectively had a positive FIT. In contrast, only two of 25 (8.0%) patients without SB lesions had a positive FIT at both thresholds (P=0.002 and 0.010 respectively). The mean fecal hemoglobin in patients with SB lesions classified as probable or suspected source of bleeding versus patients with normal SB was 345.6 ± 773 and 25.0 ± 37.7 ng/ml, respectively (P=0.025). CONCLUSION: A positive FIT can be explained by significant SB lesions detected by CE. Further studies are still needed to evaluate whether asymptomatic patients with positive FIT and nonexplanatory colonoscopy should undergo further study of the SB.

Upper and Lower Gastrointestinal Findings in PTEN Mutation-Positive Cowden Syndrome Patients Participating in an Active Surveillance Program.

OBJECTIVES: Cowden syndrome (CS), associated with germline PTEN mutations, is an autosomal-dominant disorder with increased frequencies of thyroid and breast cancers. Recent reports document the occurrence of gastrointestinal (GI) polyps and increased risk of colon cancer in PTEN mutation carriers. Studies to date, however, have not been based on mutation carriers undergoing active, systematic, routine-interval GI surveillance. Our objective is to document the upper and lower GI findings in CS patients undergoing such an active GI surveillance program. METHODS: In a 5-year period, 3,000 consecutive patients were referred to our high-risk GI cancer clinic for various reasons. Of these 3,000, 10 met full-blown clinical criteria for the diagnosis of CS. Individuals with identified PTEN mutations underwent annual upper and lower endoscopy surveillance programs using dual white light and narrow-band imaging. All biopsies including archived materials were reviewed by a single dedicated GI pathologist. RESULTS: Ten PTEN mutation carriers from different ethnic backgrounds were invited and all participated in the active GI surveillance program. Eight patients had colonic polyps, mostly hyperplastic (eight patients) and hamartomatous (five patients), but also adenomatous (three patients), ganglioneuromatous (three patients), and juvenile polyps (two patients). One patient (10%) had an early-onset rectal cancer (aged 44 years), which was null for PTEN expression on immunohistochemistry. All patients had gastric polyps and nine (90%) had duodenal polyps, mostly hyperplastic and hamartomatous. Additional three patients (30%) had adenomatous duodenal polyps. CONCLUSIONS: PTEN mutation-positive CS patients have a higher frequency of upper GI polyps than previously believed. They appear prone to develop adenomatous upper and lower tract dysplastic polyps and cancer. Thus, the polyps encountered during upper or lower endoscopy in these patients should not be automatically considered innocent hamartomas without malignant potential. Active surveillance programs in specialized centers should be considered in these patients.