Theranostic Gastrointestinal Endoscopy: Bringing Healing Light to the Lumen.

Current conventional endoscopes have restricted the accuracy of treatment delivery and monitoring. Over the past decade, there have been major developments in nanotechnology and light triggered therapy, potentially allowing a better detection of challenging lesions and targeted treatment of malignancies in the gastrointestinal tract. Theranostics is a developing form of personalized medicine because it combines diagnosis and targeted treatment delivered in one step using advances in nanotechnology. This review describes the light-triggered therapies (including photodynamic, photothermal, and photoimmunotherapies), nanotechnological advances with nanopowder, nanostent, nanogels, and nanoparticles, enhancements brought to endoscopic ultrasound, in addition to experimental endoscopic techniques, combining both enhanced diagnoses and therapies, including a developed prototype of a "smart" multifunctional endoscope for localized colorectal cancer, near-infrared laser endoscope targeting the gastrointestinal stromal tumors, the concept of endocapsule for obscure gastrointestinal bleed, and a proof-of-concept therapeutic capsule using ultrasound-mediated targeted drug delivery. Hence, the following term has been proposed encompassing these technologies: "Theranostic gastrointestinal endoscopy." Future efforts for integration of these technologies into clinical practice would be directed toward translational and clinical trials translating into a more personalized and interdisciplinary diagnosis and treatment, shorter procedural time, higher precision, higher cost-effectiveness, and less need for repetitive procedures.

A Novel Protocol Obviates Endoscope Sampling for Carbapenem-Resistant Enterobacteriaceae: Experience of a Center with a Prior Outbreak.

BACKGROUND: Numerous published outbreaks, including one from our institution, have described endoscope-associated transmission of multidrug-resistant organisms (MDROs). Individual centers have adopted their own protocols to address this issue, including endoscope culture and sequestration. Endoscope culturing has drawbacks and may allow residual bacteria, including MDROs, to go undetected after high-level disinfection. AIM: To report the outcome of our novel protocol, which does not utilize endoscope culturing, to address our outbreak. METHODS: All patients undergoing procedures with elevator-containing endoscopes were asked to permit performance of a rectal swab. All endoscopes underwent high-level disinfection according to updated manufacturer's guidance. Additionally, ethylene oxide (EtO) sterilization was done in the high-risk settings of (1) positive response to a pre-procedure risk stratification questionnaire, (2) positive or indeterminate CRE polymerase chain reaction (PCR) from rectal swab, (3) refusal to consent for PCR or questionnaire, (4) purulent cholangitis or infected pancreatic fluid collections. Two endoscopes per weekend were sterilized on a rotational basis. RESULTS: From September 1, 2015 to April 30, 2016, 556 endoscopy sessions were performed using elevator-containing endoscopes. Prompted EtO sterilization was done on 46 (8.3%) instances, 3 from positive/indeterminate PCR tests out of 530 samples (0.6%). No CRE transmission was observed during the study period. Damage or altered performance of endoscopes related to EtO was not observed. CONCLUSION: In this pilot study, prompted EtO sterilization in high-risk patients has thus far eliminated endoscope-associated MDRO transmission, although no CRE infections were noted throughout the institution during the study period. Further studies and a larger patient sample will be required to validate these findings.

Cytological specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration: sample handling and role of rapid on-site evaluation.

Recently developed, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive modality for mediastinal lymph node staging in lung cancer patients as well as for the diagnosis of mediastinal and hilar lymphadenopathy. It has been shown in systematic reviews and meta-analysis that a high diagnostic yield can be achieved with EBUS-TBNA for staging lung cancer. Though still not a standard of practice, this novel technology has attracted physicians and surgeons as an alternative modality to surgical biopsy for the assessment of the mediastinum. Standard cytology, thin layer preparations in liquid medium or cell blocks of cells obtained by EBUS-TBNA can be applicable not only for pathological diagnosis but also for further investigations such as immunohistochemistry and fluorescence in situ hybridization. In addition, samples obtained by EBUS-TBNA can also be used for molecular analysis. The key to a successful EBUS-TBNA is to understand the anatomy of the mediastinum as well as the basic steps of the procedure. Moreover, handling of the sample obtained by EBUS-TBNA is crucial for diagnosis since no amount of skill or interest of the interpreter can make up for a badly prepared sample. The goals of rapid on-site evaluation during EBUS-TBNA include determination of whether sampling of the target has been achieved and more importantly triage of samples to secondary investigations. This manuscript explains the detailed techniques of EBUS-TBNA to master this innovative procedure.

Anthropomorphic phantoms for assessment of strain imaging methods involving saline-infused sonohysterography.

Two anthropomorphic uterine phantoms were developed that allow assessment and comparison of strain imaging systems adapted for use with saline-infused sonohysterography (SIS). Tissue-mimicking (TM) materials consist of dispersions of safflower oil in gelatin. TM fibroids are stiffer than the TM myometrium/cervix, and TM polyps are softer. The first uterine phantom has 3-mm-diameter TM fibroids distributed randomly in TM myometrium. The second uterine phantom has a 5-mm and 8-mm spherical TM fibroid, in addition to a 5-mm spherical and a 12.5-mm-long (medicine capsule-shaped) TM endometrial polyp protruding into the endometrial cavity; also, a 10-mm spherical TM fibroid projects from the serosal surface. Strain images using the first phantom show the stiffer 3-mm TM fibroids in the myometrium. Results from the second uterine phantom show that, as expected, parts of inclusions projecting into the uterine cavity will appear very stiff, whether they are stiff or soft. Results from both phantoms show that although there is a five-fold difference in the Young's moduli values, there is not a significant difference in the strain in the transition from the TM myometrium to the TM fat. These phantoms allow for realistic comparison and evolution of SIS strain imaging techniques and can aid clinical personnel to develop skills for SIS strain imaging.

[Development and usage of a new laser resectoscope]. / Zur Entwicklung und Anwendung eines neuen Laserresektoskops.

BACKGROUND: Endoscopes for the application of laser energy have not been modified substantially for 3 decades. They have two essential disadvantages: the laser probe has no sufficient fixation and irrigation is ineffective in clearing endoscopic vision from hemorrhage. These defects were corrected in cooperation with the R. Wolf Company when developing a new laser resectoscope. In addition the one-handed usage was improved. MATERIAL AND METHOD: The new instrument was used in 71 of the 329 patients undergoing surgery of the prostate with KTP laser by 8 surgeons in our institution. No instrument has been damaged by laser since. Seven of eight surgeons have acknowledged the advantages and approved the new laser endoscope. CONCLUSION: The new laser resectoscope can be recommended to improve the safety of endoscopic laser surgery in general.

Endoluminal ultrasound applicator with an integrated RF coil for high-resolution magnetic resonance imaging-guided high-intensity contact ultrasound thermotherapy.

High-intensity contact ultrasound (HICU) under MRI guidance may provide minimally invasive treatment of endocavitary digestive tumors in the esophagus, colon or rectum. In this study, a miniature receive-only coil was integrated into an endoscopic ultrasound applicator to offer high-resolution MRI guidance of thermotherapy. A cylindrical plastic support with an incorporated single element flat transducer (9.45 MHz, water cooling tip) was made and equipped with a rectangular RF loop coil surrounding the active element. The integrated coil provided significantly higher sensitivity than a four-element extracorporeal phased array coil, and the standard deviation of the MR thermometry (SDT) improved up to a factor of 7 at 10 mm depth in tissue. High-resolution morphological images (T1w-TFE and IR-T1w-TSE with a voxel size of 0.25 x 0.25 x 3 mm3) and accurate thermometry data (the PRFS method with a voxel size of 0.5 x 0.5 x 5 mm3, 2.2 s/image, 0.3 degree C voxel-wise SDT) were acquired in an ex vivo esophagus sample, on a clinical 1.5T scanner. The endoscopic device was actively operated under automatic temperature control, demonstrating a high level of accuracy (1.7% standard deviation, 1.1% error of mean value), which indicates that this technology may be suitable for HICU therapy of endoluminal cancer.

Integrated endoscope for real-time 3D ultrasound imaging and hyperthermia: feasibility study.

The goal of this research is to determine the feasibility of using a single endoscopic probe for the combined purpose of real-time 3D (RT3D) ultrasound imaging of a target organ and the delivery of ultrasound therapy to facilitate the absorption of compounds for cancer treatment. Recent research in ultrasound therapy has shown that ultrasound-mediated drug delivery improves absorption of treatments for prostate, cervical and esophageal cancer. The ability to combine ultrasound hyperthermia and 3D imaging could improve visualization and targeting of cancerous tissues. In this study, numerical modeling and experimental measurements were developed to determine the feasibility of combined therapy and imaging with a 1 cm diameter endoscopic RT3D probe with 504 transmitters and 252 receive channels. This device operates at 5 MHz and has a 6.3 mm x 6.3 mm aperture to produce real time 3D pyramidal scans of 60-120 degrees incorporating 64 x 64 = 4096 image lines at 30 volumes/sec interleaved with a 3D steerable therapy beam. A finite-element mesh was constructed with over 128,000 elements in LS-DYNA to simulate the induced temperature rise from our transducer with a 3 cm deep focus in tissue. Quarter-symmetry of the transducer was used to reduce mesh size and computation time. Based on intensity values calculated in Field II using the transducer's array geometry, a minimum I(SPTA) of 3.6 W/cm2 is required from our endoscope probe in order to induce a temperature rise of 4 degrees C within five minutes. Experimental measurements of the array's power output capabilities were conducted using a PVDF hydrophone placed 3 cm away from the face of the transducer in a watertank. Using a PDA14 Signatec data acquisition board to capture full volumes of transmitted ultrasound data, it was determined that the probe can presently maintain intensity values up to 2.4 W/cm2 over indefinite times for therapeutic applications combined with intermittent 3D scanning to maintain targeting. These values were acquired using 8 cycle bursts at a prf of 6 kHz. Ex vivo heating experiments of excised pork tissue yielded a maximum temperature rises of 2.3 degrees C over 5 minutes of ultrasound exposure with an average rise of 1.8 +/- 0.2 degrees C over 5 trials. Modifications to the power supply and transducer array may enable us to reach the higher intensities required to facilitate drug delivery therapy.

[Hemorrhoid Therapy with Doppler Guided Hemorrhoidal Artery Ligation via Proctoscope KM-25. A New Alternative to Hemorrhoidectomy and Rubber Band Ligation?]. / Therapie des Hämorrhoidalleidens mittels Hämorrhoidalarterienligatur mit dem Dopplergerät KM-25. Eine neue Alternative zur Hämorrhoidektomie und Gummibandligatur nach Barron?

The aim of treating patients suffering from hemorrhoids is to eliminate or to relieve their complaints. The method should be performed on an out-patient basis, and should be painless and low rated concerning complications. The Morinaga technique fulfills these conditions, its feasibility and the results in 281 patients are presented.

A simple phantom for learning EUS-guided FNA.

BACKGROUND: The learning curve for EUS-guided FNA (EUS-FNA) is formidable. Development of a phantom to assist in teaching the technique may be beneficial. This study assessed the feasibility of using a low-cost phantom made of commonly available materials to practice EUS-FNA. METHODS: A 2500-mL barium enema bag was modified by running a plastic tube (3-mm inner diameter) through it and sealing one end. One hundred grams of standard agar were suspended in 4 liters of tap water. The broth was heated slowly to boiling. The dissolved agar was then transferred to the barium enema bag after mixing in diced carrots, elbow macaroni, peas, and fingertips of surgical gloves filled with 5 mL of normal saline solution (6 of each) to simulate solid and cystic lesions. Immersion of the phantom in a basin of water provided acoustic coupling. One end of the 3-mm plastic tubing was attached to the nozzle of a water jet device and the other end to its reservoir to create a closed system allowing water recirculation. A linear array echoendoscope and a fine needle were used to perform EUS-FNA. The analysis is descriptive. OBSERVATIONS: The phantom was readily made with inexpensive components (total cost <$50). With refrigeration the phantom was used repetitively during a 4-month period. It produced EUS images with an echotexture comparable with liver. The solid and cystic components resembled hepatic cysts and solid masses encountered when performing EUS in humans. Under EUS-guidance, fine-needle aspirates of selected lesions could be performed allowing targeting, aspiration, and sampling of selected lesions. The Doppler flow effect allowed examination of a simulated vascular structure during FNA. CONCLUSIONS: Once validated, an EUS phantom made of simple components may become an invaluable educational tool for teaching EUS-FNA. Further studies are needed to determine how it affects the skills of gastroenterologists with and without EUS experience.

[Utility of rectal endoscopic ultrasonography for digestive involvement of pelvic endometriosis. Technique and results]. / Apport de l'échoendoscopie rectale dans le bilan des atteintes digestives de l'endométriose pelvienne. Technique et résultats.

Intestinal endometriosis present in up to 37% of cases is difficult to diagnose and treatment remains complex. Until recently barium enema and colonoscopy are the only two diagnostic tools. However there were many drawbacks and technical limitations due to the particular development of the endometrial lesions with frequent respect of the mucosa. Digestive involvement was often preoperative discovery and treatment was frequently incomplete. Development of endoscopic ultrasonography has improved the potential for preoperative diagnosis of digestive endometriosis. Many publications have now demonstrated its utility. Compared to other imaging techniques endoscopic ultrasonography has better sensibility close to 100%. Endoscopic ultrasonography is superior to Magnetic Resonance Imaging for the diagnosis of rectosigmoid endometriosis. Magnetic Resonance Imaging however gives a largest view of the pelvis. Using preoperatively endoscopic ultrasonography in patients who are at risk of digestive involvement will help to choose between different therapeutic modalities and surgical techniques.

Evaluation of the colorectal wall in normal subjects and patients with ulcerative colitis using an ultrasonic catheter probe.

BACKGROUND: Ulcerative colitis is usually evaluated by barium enema and colonoscopy, methods of imaging that are limited to the mucosal surface. Endoscopic ultrasonography (EUS) is the best modality for the evaluation of transmural changes in the bowel wall. We therefore evaluated the colorectal wall in normal control subjects and patients with ulcerative colitis using an ultrasonic catheter probe. METHODS: Endoscopic ultrasound with a catheter probe was performed on 36 normal control subjects (36 examinations) and 72 patients (111 examinations) with documented ulcerative colitis. RESULTS: In normal control subjects, the total wall, mucosa, submucosa, and muscularis propria were significantly thicker in the rectum than in the colon. There was no significant difference in the thickness of the colon and rectum among different age groups or between men and women. In ulcerative colitis, we classified the boundary of each layer into three patterns (smooth, irregular, and blurred) and then classified the wall into six types. In Matts grade 2 and 3 ulcerative colitis lesions, the total wall and each layer were significantly thicker than lower grade lesions and normal control subjects. For grade 1 and most of the grade 2 lesions, the boundary of each layer was smooth. In some of the grade 3 lesions, the mucosa-submucosa and submucosa-muscularis propria layer borders were abnormal. In all grade 4 cases, the mucosa-submucosa boundary was blurred. There was some correlation between the Matts grade and EUS findings except for Matts grade 3 lesions which had various EUS patterns. CONCLUSION: Endoscopic ultrasound with a catheter probe is a useful modality for the transmural assessment of the colorectal wall and, when used in conjunction with the many clinical and endoscopic parameters currently available, may contribute to the diagnosis and treatment of ulcerative colitis.

Benign prostatic hyperplasia: US-guided transrectal urethral enlargement with radio frequency--initial results in a canine model.

PURPOSE: To enlarge the prostatic urethra with thermal coagulation with transrectal radio-frequency (RF) application in dogs. MATERIALS AND METHODS: Eight aged dogs underwent RF ablation of periurethral prostatic tissue for 6 minutes. Eighteen-gauge electrodes were placed into the periurethral tissues with a transrectal approach and ultrasound (US) guidance. Prostatic and rectal temperatures were measured during RF application. US, conventional and computed tomographic (CT) retrograde urethrography (RUG), and CT were performed immediately (n = 8) and at 3-96 days (n = 6) after ablation. Histopathologic analysis was performed at sacrifice immediately (n = 2), at 28 days (n = 2), or at 3 months (n = 4) after treatment. RESULTS: All procedures were successful with no complications and were performed in less than 30 minutes. Rectal mucosal temperature did not exceed 38 degrees C. Immediately after treatment, CT and US demonstrated 1.2-cm foci of altered periurethral tissue that corresponded to solid coagulated tissue at histopathologic analysis. By day 3, CT, RUG, and US demonstrated that these foci had begun to cavitate, resulting in enlargement of the urethra. Complete cavitation was demonstrated by day 28. Minimal reduction in the degree of urethral enlargement was noted by day 60, but narrowing, urethral strictures, or fistulas were not observed at 3 months. At histopathologic analysis, focal cavitary enlargement with at least doubling of the urethral diameter and with normal urothelium was noted in all dogs surviving at least 28 days. CONCLUSION: Transrectal RF urethral enlargement is feasible and safe in animals and merits investigation for alleviating urethral obstruction due to benign prostatic hyperplasia.

Transperineal radiofrequency interstitial tumor ablation (RITA) of the prostate.

The purpose of this study was to investigate the safety and feasibility of radiofrequency interstitial tumor ablation (RITA) in localized prostate cancer (PCa) and to assess the predictability of the lesions obtained. In 10 patients with localized PCa (mean age 70.4 years), a total of 21 marker lesions were induced under general (n = 3), spinal (n = 4), or local anesthesia only (n = 3). Radiofrequency energy was delivered transperineally under transrectal ultrasound (TRUS) guidance. Radical prostatectomy was performed in all patients 1-7 days after RITA. The findings of intraoperative TRUS and histologic examination of the specimen were correlated. Lesions 2 x 2 x 2 cm were targeted. Postoperatively, patients were catheterized for an average of 1.8 days (range 1-3). Average lesion diameters defined by coagulative necrosis at histologic examination were 2.20 +/- 0.23 x 2.10 +/- 0.31 x 2.38 +/- 0.14 cm (average volume 5.86 +/- 1.63 cm3). Lesions were well defined and did not extend beyond the prostatic capsule. No complications (e.g., rectal wall injury) were noted. RITA-induced lesions were safe, feasible, technically simple, and resulted in lesions well predictable in size and location. On histologic examination, well-defined areas of coagulative necrosis were documented. No damage to the periprostatic tissue was noted. The procedure can be performed with spinal or local anesthesia only.

[Endorectal echotomography in assessing the spread of rectal cancer]. / Endorektal'naia ékhotomografiia v otsenke rasprostranennosti raka priamoi kishki.

Endorectal echotomography is one of modern methods to diagnose rectal carcinoma spreading. On the basis of examination of 56 patients with the above pathology the authors have studied the ultrasonic semiotics of tumourous lesion of rectum and its regional lymphatic apparatus during different stages of the illness. The article contains an outline of the methods of investigation. The findings from ultrasonic diagnosis were compared with the results of clinical, endoscopic investigations and histological analysis of the operative material. A high diagnostic value was shown of the method in the assessment of local spread of the tumor: sensitivity--94.6%, specificity--83.3%, general precision--91.8%. Endorectal ultrasonic tomography permits the enlarged pararectal lymphatic nodes to be visualized but the method's demerit is lack of ultrasonic criteria in the differential diagnosis between the metastatic lesion of the lymphatic node and inflammatory type changes.

[Magnetic resonance tomography and endosonography in the preoperative staging of advanced rectal carcinomas after hyperthermoradiochemotherapy]. / Magnetresonanztomographie und Endosonographie beim präoperativen Staging fortgeschrittener Rektumkarzinome nach Hyperthermoradiochemotherapie.

PURPOSE: Comparison of diagnostic accuracy of staging of endorectal sonography (ES) and body coil MRI after preoperative hyperthermoradiochemotherapy in patients with advanced rectal cancer. METHODS: Prospective analysis of MRI and ES in 30 patients after hyperthermoradiochemotherapy and correlation with histopathological patterns. RESULTS: T-staging by MRI was correct in 47% and by ES in 53% of the cases. Despite similar accuracy of staging in T0- and T1-tumours, we found different accuracies concerning T2-tumour staging about 63% versus 73% (MRI/ES), concerning perirectal infiltration 70% for both techniques, concerning invasion of adjacent organs 90% versus 87%, and concerning lymph node metastases without respect to the N-stage 63% versus 63%. CONCLUSION: Both imaging modalities provide useful information for operation planning despite limited accuracy after hyperthermoradiochemotherapy. The body coil MRI does not seem to be severely inferior to ES in post-therapeutic staging, despite better contour line imaging by ES. With respect to the determination of invasion of other organs, MRI seems to be more useful.

[Endosonography of the pharynx]. / Endosonographie des Pharynx.

BACKGROUND: Endosonography is a diagnostic tool for the examination of tumors of the oral cavity. The pharynx is usually not assessable for conventional endosonography due to problems with the placement of the probe in deeper areas of the pharynx. PATIENTS: A fingertop ultrasonography probe was combined with a stick allowing the user to locate the probe in deeper areas of the pharynx. The stick had two flexible joints and a device for attaching the probe in the front. We evaluated 48 patients with tumors of the posterior wall of the pharynx (n = 6), lateral wall of the pharynx (n = 7), tonsil (n = 17), sinus piriformis (n = 13), and nasopharynx (n = 5) during preoperative tumor endoscopy under general anesthesia. Thirty-two patients suspected of having a tonsillar abscess were examined under local anesthesia. RESULTS: The evaluation of the tumor dissemination and the determination of the relationship between the tumor and the internal carotid artery was excellent for tumors of the posterior and lateral wall of the pharynx. The investigation of tumors of the sinus piriformis and the nasopharynx was difficult and tumor growth could not be determined normally with endosonography. In four cases, retropharyngeal lymph nodes could be detected. The sensitivity for the diagnosis of tonsillar abscesses was 84%. CONCLUSION: Endosonography of the deeper areas of the pharynx seems to be a useful instrument for investigating growth of tumors at the lateral and posterior wall of the pharynx. Endosonographic results might be helpful for deciding between endoscopic and external approaches. Endosonography is not sufficiently sensitive for diagnosing tonsillar abscesses, but might be helpful in clinically difficult cases.