Background: The small bowel is the most commonly affected site of Crohn’s disease (CD) although it may involve any part of the gastrointestinal tract. The current methodologies for examining the small bowel are x ray and endoscopy. Aims: To evaluate, for the first time, the effectiveness of wireless capsule endoscopy in patients with suspected CD of the small bowel undetected by conventional modalities, and to determine the diagnostic yield of the M2A Given Capsule. Patients: Seventeen patients (eight males, mean age 40 (15) years) with suspected CD fulfilled study entry criteria: nine had iron deficiency anaemia (mean haemoglobin 10.5 (SD 1.8) g%), eight had abdominal pain, seven had diarrhoea, and three had weight loss. Small bowel x ray and upper and lower gastrointestinal endoscopic findings were normal. Mean duration of symptoms before diagnosis was 6.3 (SD 2.2) years. Methods: Each subject swallowed an M2A Given Capsule containing a miniature video camera, batteries, a transmitter, and an antenna. Recording time was approximately eight hours. The capsule was excreted naturally in the patient’s bowel movement, and the data it contained were retrieved and interpreted the next day. Results: Of the 17 study participants, 12 (70.6%, six males, mean age 34.5 (12) years) were diagnosed as having CD of the small bowel according to the findings of the M2A Given Capsule. Conclusions: Wireless capsule endoscopy diagnosed CD of the small bowel (diagnostic yield of 71%). It was demonstrated as being an effective modality for diagnosing patients with suspected CD undetected by conventional diagnostic methodologies.

Background and study aims: Population-based screening for colorectal cancer is widely recommended, with conventional colonoscopy considered to be the preferred diagnostic modality. However, compliance with screening colonoscopy is low and manpower capacity is limited. Capsule endoscopy might therefore represent a desirable alternative strategy. Patients and methods: The PillCam Colon capsule endoscope was prospectively tested in a multicenter setting. The indications for endoscopy in the enrolled patients included colorectal cancer screening (43 %), postpolypectomy surveillance (26 %), and lower gastrointestinal signs and symptoms (31 %). Study subjects underwent colon preparation and then ingested the capsule on the morning of the examination, with conventional colonoscopy being performed the same day. The PillCam Colon capsule findings were reviewed by three experts in capsule endoscopy who were blinded to the conventional colonoscopy findings. Results: A total of 91 subjects were enrolled in three Israeli centers (55 men, 36 women; mean age 57), and the results were evaluable in 84 cases. The capsule was excreted within 10 hours in 74 % of the patients and reached the rectosigmoid colon in the other 16 %. Of the 84 evaluable patients, 20 (24 %) had significant findings, defined as at least one polyp of 6 mm or more in size or three or more polyps of any size: 14/20 (70 %) were identified with the capsule and 16/20 (80 %) were identified by conventional colonoscopy. Polyps of any size were found in 45 patients, 34/45 (76 %) found by the capsule and 36/45 (80 %) by conventional colonoscopy. In comparison with conventional colonoscopy, false-positive findings on PillCam Colon capsule examination were recorded in 15/45 cases (33 %). There were no adverse events related to the capsule endoscopy. Conclusions: PillCam Colon capsule endoscopy appears to be a promising new modality for colonic evaluation. Further improvements in the procedure will probably increase capsule examination completion and polyp detection rates. Additional studies are needed to evaluate the accuracy of PillCam Colon endoscopy in other patient populations with different prevalence levels of colonic disease.

Background and study aims: A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. Patients and methods: In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. Results: 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps ≥ 6 mm was 89 % (95 % confidence interval [CI] 70 – 97) and for those with polyps ≥ 10 mm it was 88 % (95 %CI 56 – 98), with specificities of 76 % (95 %CI 72 – 78) and 89 % (95 %CI 86 – 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 – 86). Conclusions: The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial–mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target. Significance Pancreatic cancer is still one of the major challenges in clinical oncology. Mutant KRAS is a driving oncogene in the majority of human pancreatic cancer cases. We have made an effort to meet this challenge by developing a therapeutic platform for local and prolonged delivery of siRNA. Our results show that the siRNA targeted against KRAS mutations with a local prolonged release system knocks down KRAS expression in vitro and in vivo, leading to an antitumor effect. Our report describes an applicable and efficient delivery method of siRNA that overcomes the major obstacles of toxicity and organ accessibility. Notably our approach enabled the conversion of KRAS from a nondruggable to a potentially druggable cancer target.

Background/Aim: Irritable bowel syndrome is one of the most common gastrointestinal disorders in Western society, affecting around 15% of the population, especially young adults. The cause(s) of irritable bowel syndrome and effective treatment(s) have remained elusive. This study aimed at exploring the therapeutic value of acupuncture by comparing the responses of irritable bowel syndrome sufferers to true acupuncture versus sham acupuncture in a controlled double-blind study. Methods: Twenty-five patients who fulfilled the Rome criteria (irritable bowel syndrome symptoms persisting for more than 1 year) comprised the final study population. They were recruited through a ‘call for’ bulletin sent to gastroenterologists practicing in the region of our medical center. True acupuncture was performed at LI-4 (colonic meridian, needle only) and sham acupuncture at BL-60 (urinary vesicle meridian, needle only). Patient assignment to one of the two groups was random. Results: The effect of the first true acupuncture on overall symptoms and abdominal pain was a clear and significant improvement (p = 0.05). No comparable effect was seen in the second session. Conclusions: Although the true acupuncture results were consistently better, no difference was found between the two groups in the overall statistical analysis. We could not show a therapeutic benefit of this treatment modality in irritable bowel syndrome.