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Objective Endoscopic ultrasound is the standard procedure for the diagnosis of pancreatic lesions and new needles have been developed to improve tissue acquisition (FNB). Rapid onset evaluation (ROSE) decreases the number of needle passes but is not always available. We introduced an easy and rapid method of direct classification of EUS-FNB sample namely Visual on-site evaluation (VOSE). Aims To assess the accuracy of VOSE in predicting the histological adequacy of specimens. To evaluate the diagnostic power of FNB and the rate of core tissue obtained. Methods Prospective single center study on patients with pancreatic lesions that underwent EUS-FNB. VOSE parameters were presence of blood, macroscopic visible core (MVC), number, color and length of specimen. The association between VOSE tool and histological adequacy was assessed. Fisher’s exact test and Student’s t-test used to compare categorical and continuous variables. Logistic regression analysis was used to assess association between variables. Results 99 patients (58.6% male; mean age 68.4 ± 10) enrolled, including 102 lesions. Total number of passes was 358 with median number of 4 (range, 2–4). The 92.7% of samples were adequate and it was higher with the 22-G needle than with 25G (96.5% vs 89.2% p 0.01). VOSE “red-mixed specimen” was associated with a higher probability of histological adequacy (OR 2.39 95% CI 1.03–5.42 p = 0.04). Conclusions The VOSE tool “red-mixed specimen” can be used to predict the histological adequacy and guide the number of needle passes. Overall, FNB provides a high rate of adequate and diagnostic specimen and high rate of core tissue especially with the 22G needle.

Background and aim Endoscopic full-thickness resection(EFTR) with FTRD® in colo-rectum may be useful for several indications.The aim was to assess its efficacy and safety. Material and methods In this retrospective multicenter study 114 patients were screened; 110 (61M/49F, mean age 68 ± 11 years, range 20–90) underwent EFTR using FTRD®. Indications were:residual/recurrent adenoma (39), incomplete resection at histology (R1 resection) (26), non-lifting lesion (12), adenoma involving the appendix (2) or diverticulum (2), subepithelial lesions(10), suspected T1 carcinoma (16), diagnostic resection (3). Technical success (TS: lesion reached and resected), R0 resection (negative lateral and deep margins),EFTR rate(all layers documented in the specimen) and safety have been evaluated. Results TS was achieved in 94.4% of cases. EFTR was achieved in 91% with lateral and deep R0 resection in 90% and 92%. Mean size of specimens was 20 mm (range 6–42). In residual/recurrent adenomas, final analysis revealed: low-risk T1 (11), adenoma with low-grade dysplasia (LGD) (24) and high-grade dysplasia (HGD) (3), scar tissue (1). Histology reports of R1 resections were: adenoma with LGD (6), with HGD (1), low-risk (6) and high-risk (1) T1, scar tissue (12). Non-lifting lesions were diagnosed as: adenoma with HGD (3), low-risk (7) and high risk (2) T1. Adverse clinical events occurred in 12 patients (11%),while adverse technical events in11%. Three-months follow-up was available in 100 cases and residual disease was evident in only seven patients. Conclusions EFTR using FTRD® seems to be a feasible, effective and safe technique for treating selected colo-rectal lesions. Comparative prospective studies are needed to confirm these promising results.

The treatment of choice for the unresectable cholangiocarcinoma is based on biliary decompression procedures. Despite stent placement is the standard of care, it is related to well-known complications. Hence, alternative techniques were proposed. Ideally, they should guarantee an adequate intraductal disobstruction, without injuring the surrounding tissues.This pre-clinical study aims to investigate the thermal effects of the laser ablation (LA) in the biliary tree, in terms of intraductal and surrounding tissue temperature achieved with different laser settings. The common bile ducts (in their upper and lower portions) of two pigs were ablated for 6 minutes with a diode laser at 3 W and 5 W. A custom-made laser applicator was used to obtain a circumferential ablation within the ducts. The intraductal temperature (T id ) was monitored by means of a fiber Bragg grating (FBG) sensor, while an infrared thermal camera monitored the T distribution in the surrounding tissues (T sup ). A maximum T difference of 65 °C and 57 °C was evidenced between the two power settings for the T id measured in the upper and lower ducts, respectively. The mean difference between T id and the averaged T sup values was evaluated. At 5 W, a difference of 37±3 °C and 44±10 °C were obtained for the upper and lower ducts, respectively. At 3 W, a T difference of 2±1 °C was obtained for the upper biliary duct, while a difference of 8±1 °C was documented for the lower duct. Based on the results obtained in this preliminary study, the possibility to equip the laser probe with temperature sensor can improve the control and the safety of the procedure; this solution will guarantee the monitoring of the treatment while preserving the lumen and the surrounding structures.

Laser Ablation (LA) is a minimally invasive technique for tumor removal. The laser light is guided into the target tissue by a fiber optic applicator; thus the physical features of the applicator tip strongly influence size and shape of the tissue lesion. This study aims to verify the geometry of the lesion achieved by a tapered-tip applicator, and to investigate the percentage of thermally damaged cells induced by the tapered-tip fiber optic applicator. A theoretical model was implemented to simulate: i) the distribution of laser light fluence rate in the tissue through Monte Carlo method, ii) the induced temperature distribution, by means of the Bio Heat Equation, iii) the tissue injury, by Arrhenius integral. The results obtained by the implementation of the theoretical model were experimentally assessed. Ex vivo porcine liver underwent LA with tapered-tip applicator, at different laser settings (laser power of 1 W and 1.7 W, deposited energy equal to 330 J and 500 J, respectively). Almost spherical volume lesions were produced. The thermal damage was assessed by measuring the diameter of the circular-shaped lesion. The comparison between experimental results and theoretical prediction shows that the thermal damage discriminated by visual inspection always corresponds to a percentage of damaged cells of 96%. A tapered-tip applicator allows obtaining localized and reproducible damage close to spherical shape, whose diameter is related to the laser settings, and the simple theoretical model described is suitable to predict the effects, in terms of thermal damage, on ex vivo liver. Further trials should be addressed to adapt the model also on in vivo tissue, aiming to develop a tool useful to support the physician in clinical application of LA.

Thermal therapies are minimally invasive procedures used to locally remove tumor in several organs by means of cytotoxic temperature. Among several techniques, laser ablation (LA) is appreciated for the possibility to be performed by flexible optical fibers, hence to be coupled with MR imaging for procedure guidance. In this work, we present the first in vivo trial on pig pancreas undergoing LA and simultaneous multipoint temperature monitoring by means of fiber optic sensors (Fiber Bragg gratings -FBGs-). The clinical procedure has been performed through percutaneous access to the pancreas. The optical output of the FBGs, measuring both the temperature evolution and the breathing movement, is post-processed to neglect possible artifacts on the signal. Temperature data were also employed to estimate the thermal dose induced within the pancreas. The findings of this study may be useful for the definition of the safe LA to the patients, and allow understanding the effects of the laser light on the pancreatic tissue, paving the way for a controlled therapy in clinical settings.

Radiofrequency ablation (RFA) is a minimally invasive procedure used to treat tumors by means of hyperthermia, mostly through percutaneous approach. The tissue temperature plays a pivotal role in the achievement of the target volume heating, while sparing the surrounding healthy tissue from thermal damage. Several techniques for thermometry during RFA are investigated, most of them based on the use of single-point measurement system (e.g., thermocouples). The measurement of temperature map is crucial for the real-time control and fine adjustment of the treatment settings, to optimize the shape and size of the ablated volume. The recent interest about fiber optic sensors and, among them, fiber Bragg gratings (FBGs) for the monitoring of thermal effects motivated further investigation. In particular, the feature of FBGs to form an array of several elements, thus to be inscribed within the same fiber, allows the use of a single probe for the multi-points monitoring of the tissue temperature during RFA. Hence, the aim of this study is the development and characterization of a needle-like probe embedding an array of three FBGs, which was tested on pig liver during in vivo trials. The needle allows a safe and easy insertion of the fiber optic within the liver. It was inserted by ultrasound guidance into the liver, and monitored the change of tissue temperature during RFA controlled by the roll-off technique. Also the measurement error induced by breathing movements of the liver was assessed (less than 3 °C). Results encourage the use of the probe in clinical settings, as well as the improvement of some features, e.g., a higher number of FBGs for performing quasi-distributed measurement. © 2016 IEEE.

In this work, we investigated the temperature increment experienced by biological tissue during radiofrequency ablation (RFA). The measurements were performed by using two custom-made thermal probes based on fiber optic sensors (fiber Bragg gratings, FBGs). The two probes embed a total of 9 FBGs. Experiments were performed during RFA of an ex vivo healthy porcine liver. The RFA heating module was equipped with 5 thermocouples. Results show that the temperature increment close to the applicator (i.e., 0.6 cm-0.7 cm) reaches the temperature which is set as a target on the RFA module (i.e., approximately 100 °C). The distance from the applicator also has an impact on the dynamics of the heating phenomenon: at short distances the tissue temperature reaches a steady state condition after a few minutes, on the other hand the sensors placed at a distance ≥2cm did not reach the steady-state conditions during the 14-minute procedure. The multipoint temperature monitoring, which uses sensors at several distances from the applicator, can provide useful information regarding the boundary of damaged volume. This approach can be combined with the monitoring temperature system embedded in the heating equipment, to better control the damaged volume, and to improve the treatment outcomes.

Laser-induced interstitial thermotherapy (LITT) has been recently applied to pancreas in animal models for ablation purpose. Assessment of thermal effects due to the laser-pancreatic tissue interaction is a critical factor in validating the procedure feasibility and safety. A mathematical model based on bioheat equation and its experimental assessment was developed. The LITT procedure was performed on 40 ex vivo porcine pancreases, with an Nd:YAG (1064 nm) energy of 1000 J and power from 1.5 up to 10 W conveyed by a quartz optical fiber with 300 μm diameter. Six fiber Bragg grating sensors have been utilized to measure temperature distribution as a function of time at fixed distances from the applicator tip within pancreas undergoing LITT. Simulations and experiments show temperature variations Δ T steeply decreasing with distance from the applicator at higher power values: at 6 W, ∆T40 °C at 5 mm and Δ T is approximately equal to 5 °C at 10 mm. Δ T nonlinearly increases with power close to the applicator. Ablated and coagulated tissue volumes have also been measured and experimental results agree with theoretical ones. Despite the absence of data in the current literature on pancreas optical parameters, the model allowed a quite good prediction of thermal effects. The prediction of LITT effects on pancreas is necessary to assess laser dosimetry.

Estimation of optical properties of biologic tissues is determinant for laser dosimetry in medical applications. Tissues highly absorb and scatter the light in near infrared spectrum, where the laser provides therapeutic effects. Novel frontiers of clinical practice, e.g., the employment of laser light for the treatment of pancreatic cancer, require information about pancreas-laser interaction, which are crucial for therapy management. The property of biological tissues to scatter the light traveling through is described by the anisotropy coefficient (g). The relationship between g and the angular distribution of the scattered light is described by Henyey-Greenstein phase function. The measurement of angular distribution of scattered light is performed by the goniometric technique. This paper describes the estimation of g of ex vivo pancreas at 1064 nm, performed by a goniometric-based system, where a photodetector measures intensities of scattered light at fixed angles between -120° and 120°. A two-term Henyey-Greenstein phase function has been employed to estimate anisotropy coefficient for forward (gfs) and backward scattering (gbs). Experimental trails were performed to assess the repeatability of measurement system: percentage value of standard deviation is generally lower than 8% for angles higher (lower) than 13° (13°). Measurements were performed for the first time on healthy swine pancreas, aiming to investigate the influence of coagulation temperature: gfs decreases from 0.94 (at 25 °C) to 0.93 (at 80 °C). Afterwards, the same set up has been employed for the estimation of g of human pancreas affected by neuroendocrine tumor, which presented an estimated values for gfs of 0.89.

Laser Ablation (LA) is a minimally-invasive procedure for tumor treatment. LA outcomes depend on the heat distribution inside tissues and require accurate temperature measurement during the procedure. Magnetic resonance imaging (MRI) allows a non-invasive and three-dimensional thermometry of the organ undergoing LA. In this study, the temperature distribution within two swine pancreases and three swine livers undergoing LA (Nd:YAG, power: 2 W, treatment time: 4 min) was monitored by a 1.5-T MR scanner, utilizing two T 1 -weighted sequences (IRTF and SRTF). The signal intensity in four regions of interest, placed at different distances from the laser applicator, was related to temperature variations monitored in the same regions by twelve fiber Bragg grating sensors. The relationship between the signal intensity and temperature increase was calculated to obtain the calibration curve and to evaluate accuracy, sensibility and precision of each sequence. This is the first study of MR-based thermometry during LA on pancreas. More specifically, the IRTF sequence provides the highest temperature sensitivity in both liver (1.8 ± 0.2 °C −1 ) and pancreas (1.8 ± 0.5 °C −1 ) and the lowest precision and accuracy. SRTF sequence on pancreas presents the highest accuracy and precision (MOD SFRT = −0.1 °C and LOA SFRT = [−2.3; 2.1] °C).

Laser interstitial thermotherapy (LITT) is a minimally invasive technique used to thermally destroy tumour cells. Being based on hyperthermia, LITT outcome depends on the temperature distribution inside the tissue. Recently, CT scan thermometry, based on the dependence of the CT number (HU) on tissue temperature (T) has been introduced during LITT; it is an attractive approach to monitor T because it overcomes the concerns related to the invasiveness. We performed LITT on nine ex vivo swine livers at three different laser powers, (P=1.5 W, P=3 W, P=5 W) with a constant treatment time t=200 s; HU is averaged on two ellipsoidal regions of interest (ROI) of 0.2 cm2, placed at two distances from the applicator (d=3.6 mm and d=8.7 mm); a reference ROI was placed away from the applicator (d=30 mm). The aim of this study is twofold: 1) to evaluate the effect of the T increase in terms of HU variation in ex vivo swine livers undergoing LITT; and 2) to estimate the P value for tissue vaporization. To the best of our knowledge, this is the first study focused on the HU variation in swine livers undergoing LITT at different P. The reported findings could be useful to assess the effect of LITT on the liver in terms of both T changes and tissue vaporization, with the aim to obtain an effective therapy.

Laser interstitial thermotherapy (LITT) is employed to destroy tumors in organs, and its outcome strongly depends on the temperature distribution inside the treated tissue. The recent introduction of computed tomography (CT) scan thermometry, based on the CT number dependence of the tissue with temperature, overcomes the invasiveness of other techniques used to monitor temperature during LITT. The averaged CT number (ROI = 0.02 cm2) of an ex vivo swine pancreas is monitored during LITT (Nd:YAG laser power of 3 W, treatment time: 120 s) at different distances from the applicator (from 4 to 30 mm). The averaged CT number shows a clear decrease during treatment: it is highest at 4 mm from the applicator (mean variation in the whole treatment of -0.256 HU s-1) and negligible at 30 mm, since the highest temperature increase is present close to the applicator (i.e., 45 °C at 4 mm and 25 °C at 6 mm). To obtain the relationship between CT numbers and pancreas temperature, the reference temperature was measured by 12 fiber Bragg grating sensors. The CT number decreases as a function of temperature, showing a nonlinear trend with a mean thermal sensitivity of -0.50 HU °C-1. Results here reported are the first assessment of pancreatic CT number dependence on temperature, at the best of our knowledge. Findings can be useful to further investigate CT scan thermometry during LITT on the pancreas. © 2013 Institute of Physics and Engineering in Medicine.

BACKGROUND & AIMS: Tumor necrosis factor alpha (TNF-alpha) release plays a pivotal role in the pathogenesis of liver injury induced by lipopolysaccharide (LPS) administration in D-galactosamine (GalN)- sensitized mice. Interleukin (IL) 10 is an anti-inflammatory cytokine that inhibits TNF-alpha synthesis and release both in vitro and in vivo and prevents lethality from experimental endotoxemia. The present study was designed to ascertain whether in vivo treatment with IL-10 protects mice against LPS/GalN-induced liver injury. METHODS: Mice were treated with an intraperitoneal dose of LPS/GalN with or without IL-10 pretreatment. Liver injury was assessed biochemically and histologically, and plasma TNF-alpha levels, liver myeloperoxidase activity, and adhesion molecule expression were determined. RESULTS: Administration of LPS in GalN-sensitized mice caused lethal shock and massive hepatic necrosis in almost 100% of the mice. The effect was associated with a significant increase in plasma TNF-alpha concentrations, liver myeloperoxidase activity, and up-regulation of adhesion molecules on liver specimens and circulating neutrophils. Pretreatment with IL-10 reduced plasma TNF-alpha concentrations and LPS/GalN-induced liver injury and lethality. Moreover, IL-10 reduced the LPS/GalN-induced liver neutrophil margination and up-regulation of adhesion molecules both on liver specimens and circulating neutrophils. CONCLUSIONS: The present results suggest that IL-10 therapy could be useful in the treatment of TNF-alpha-mediated liver diseases. (Gastroenterology 1996 Sep;111(3):736-44)

e15246 Background: Satellite repeat RNAs HSAT II belongs to an heterogeneous group of non-coding transcripts, namely long non-coding RNAs. HSAT II transcripts, recently found in pancreatic ductal a...

Patients who are undergoing endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for suspected pancreatic tumors frequently undergo endoscopic retrograde cholangiopancreatography (ERCP) for palliation of their symptoms. Performing EUS-FNA and ERCP in tandem may be cost-effective and may reduce procedure time, but the potential risks associated with this approach have not been clearly defined in the literature. We report two patients who underwent same-day therapeutic ERCP after transduodenal EUS-FNA for pancreatic tumors. Endoscopic biliary manipulation during ERCP aggravated an inadvertent and subclinical needle puncture injury to the bile duct sustained during the preceding EUS-FNA. This resulted in leakage of bile into the retroperitoneal space, and both patients required laparotomy and surgical drainage. Additional clinical evidence is needed to clarify these issues and to determine whether it would be prudent to perform therapeutic ERCP prior to diagnostic transduodenal EUS-FNA when these two procedures are planned as sequential or same-day procedures.

Neutrophil adherence within the gastric microcirculation is thought to be a major step in the pathogenesis of gastric mucosal damage induced by indomethacin. Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations. Rats were treated with 20 mg/kg oral indomethacin, pretreated with vehicle or with four different doses of pentoxifylline intraperitoneally, and killed after three hours. The gross gastric mucosal injury, neutrophil margination into the gastric microcirculation, mucosal concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha), and PGE2 and serum TNF alpha values were measured. Whether the pentoxifylline induced protection involved nitric oxide mediated pathways or gastric acid secretion was evaluated. The data indicate that pentoxifylline reduces indomethacin induced mucosal damage and neutrophil margination in a dose dependent manner without exerting any effect on gastric mucosal prostaglandin concentrations. The maximally effective dose (200 mg/kg) of pentoxifylline reduced gastric damage by 90% and slightly stimulated acid secretion. The effect of pentoxifylline was not affected by pretreatment with the nitric oxide inhibitor. Pentoxifylline prevented the indomethacin induced increase in TNF alpha concentrations in a dose dependent fashion. Serum TNF alpha values were 30.5 (7.0) IU/ml (mean (SEM)) in rats treated with indomethacin alone and 5.0 (2.5) IU/ml (p < 0.01) in rats treated with indomethacin plus 200 mg/kg pentoxifylline. Pentoxifylline, therefore, prevents the acute gastric mucosal damage and neutrophil margination induced by indomethacin and reduces indomethacin induced release of TNF alpha.