A biomarker panel predicts progression of Barrett's esophagus to esophageal adenocarcinoma.

Progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) is uncommon but the consequences are serious. Predictors of progression are essential to optimize resource utilization. This study assessed the utility of a promising panel of biomarkers applicable to routine paraffin embedded biopsies (FFPE) to predict progression of BE to EAC in a large population-based, nested case-control study.We utilized the Amsterdam-based ReBus nested case-control cohort. BE patients who progressed to high-grade dysplasia (HGD)/EAC (n = 130) and BE patients who never progressed (n = 130) were matched on age, sex, length of the BE segment, and duration of endoscopic surveillance. All progressors had minimum 2 years of endoscopic surveillance without HGD/EAC to exclude prevalent neoplasia. We assessed abnormal DNA content, p53, Cyclin A, and Aspergillus oryzae lectin (AOL) in FFPE sections. We performed conditional logistic regression analysis to estimate odds ratio (OR) of progression based on biomarker status.Expert LGD (OR, 8.3; 95% CI, 1.7-41.0), AOL (3 vs. 0 epithelial compartments abnormal; OR, 3.6; 95% CI, 1.2-10.6) and p53 (OR, 2.3; 95% CI, 1.2-4.6) were independently associated with neoplastic progression. Cyclin A did not predict progression and DNA ploidy analysis by image cytometry was unsuccessful in the majority of cases, both were excluded from the multivariate analysis. The multivariable biomarker model had an area under the receiver operating characteristic curve of 0.73.Expert LGD, AOL, and p53 independently predict neoplastic progression in BE patients and are applicable to routine practice. These biomarkers can aid in selecting patients for endoscopic ablation or more intensive surveillance.

Association of sporadic and familial Barrett's esophagus with breast cancer.

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Based on striking aggregation of breast cancer and BE/EAC within families as well as shared risk factors and molecular mechanisms of carcinogenesis, we hypothesized that BE may be associated with breast cancer. Pedigree analysis of families identified prospectively at multiple academic centers as part of the Familial Barrett's Esophagus Consortium (FBEC) was reviewed and families with aggregation of BE/EAC and breast cancer are reported. Additionally, using a matched case-control study design, we compared newly diagnosed BE cases in Caucasian females with breast cancer (cases) to Caucasian females without breast cancer (controls) who had undergone upper endoscopy (EGD). Two familial pedigrees, meeting a stringent inclusion criterion, manifested familial aggregation of BE/EAC and breast cancer in an autosomal dominant inheritance pattern with incomplete penetrance. From January 2008 to October 2016, 2812 breast cancer patient charts were identified, of which 213 were Caucasian females who underwent EGD. Six of 213 (2.82%) patients with breast cancer had pathology-confirmed BE, compared to 1 of 241 (0.41%) controls (P-value < 0.05). Selected families with BE/EAC show segregation of breast cancer. A breast cancer diagnosis is marginally associated with BE. We postulate a common susceptibility between BE/EAC and breast cancer.

Lymph node characterization in vivo using endoscopic ultrasound spectrum analysis with electronic array echo endoscopes.

Our purpose was to demonstrate the use of radiofrequency spectral analysis to distinguish between benign and malignant lymph nodes with data obtained using electronic array echo endoscopes, as we have done previously using mechanical echo endoscopes. In a prospective study, images were obtained from eight patients with benign-appearing lymph nodes and 11 with malignant lymph nodes, as verified by fine-needle aspiration. Midband fit, slope, intercept, correlation coefficient, and root-mean-square (RMS) deviation from a linear regression of the calibrated power spectra were determined and compared between the groups. Significant differences were observable for mean midband fit, intercept, and RMS deviation (t test P < 0.05). For benign (n = 16) vs. malignant (n = 12) lymph nodes, midband fit and RMS deviation provided classification with 89 % accuracy and area under receiver operating characteristic (ROC) curve of 0.95 based on linear discriminant analysis. We concluded that the mean spectral parameters of the backscattered signals from electronic array echo endoscopy can provide a noninvasive method to quantitatively discriminate between benign and malignant lymph nodes.

Tissue apposition system: new technology to minimize surgery for endoscopically unresectable colonic polyps.

OBJECTIVE: This is the first clinical series using the Tissue Apposition System (TAS) device in a feasibility study of polypectomy as an alternative to laparoscopic colectomy (LC) for endoscopically unresectable polyps. TAS is a novel T-tag system for endoscopic placement of sutures, facilitating closure of larger defects from advanced endoluminal or transluminal endoscopic procedures. Such novel instrumentation may reduce risk and accelerate recovery. METHODS: After institutional review board approval, patients with endoscopically unresectable polyps who would otherwise require LC were enrolled. The polyp site was visualized by colonoscopy and resected with laparoscopic assistance, using endoscopic mucosal resection (EMR) or submucosal dissection. After confirming benign disease by frozen section, the polypectomy site was closed by TAS under laparoscopic observation to avoid injury to surrounding structures. Follow-up colonoscopy was performed at 3 months. RESULTS: Seven patients were recruited (5 men; mean age, 66 years). Polyps were from 20 to 50 (mean, 30) mm in diameter; six were in the right colon, and three were on the mesenteric border of the bowel. All final pathology was benign. Mean EMR time was 29 min, mean time taken for TAS was 37 min, and mean total operative time was 199 min. Two TAS procedures required conversion to LC (one unresectable polyp and one device failure). Five TAS procedures were completed, with a mean hospital stay of 1.2 days, and no complications. Follow-up colonoscopy revealed healing without polyp recurrence in any case. One patient (initial 5-cm sigmoid polyp) developed a very mild clinically asymptomatic stricture in the sigmoid colon. CONCLUSIONS: This initial human experience demonstrates that TAS can be used safely in the colon under laparoscopic control. TAS permits safe closure of defects after endoscopic polypectomy of selected and otherwise unresectable polyps. Such technology may potentially avoid the need for LC and permit rapid recovery with short hospital stay.

[Impact of small molecules on intermolecular interactions underlying the ligand technologies in laboratory diagnosis].

Hydrogen peroxide has been found to have a distorting effect on the quality of determination of the serological markers of hepatitis B and C, transglutaminase antibodies: an increase in the percent of false higher (anti-HBsAg, HBeAg, anti-HCV) and false lower (anti-HBeAg) values, and on the results of PCR-based diagnosis (PCR inhibition that was more pronounced especially in low viremia). A possibility of interference of measurement results in the blood metabolite pool should be taken into account in the use of high-technology methods of laboratory analysis. In particular, there may be changes in the detection of immunological and molecular biological methods in hyperpyruvatemia and hyperoxaloacetatemia, with elevated peroxide concentrations during pathological processes.

[AB0 blood group-associated biological variability in the content of metabolites].

The performed studies provided new evidence for biological variability in clinically important analytes, estimated a possible association of the metabolic features and the conservative genetic attribute--the ABO blood group. Certain features in the levels of protein, carbohydrate, lipid, and mineral metabolic parameters were revealed in relation to various blood groups.

Endoscopic full-thickness resection of gastric tumors using a novel grasp-and-snare technique: feasibility in ex vivo and in vivo porcine models.

BACKGROUND AND STUDY AIMS: Endoscopic full-thickness resection (EFTR) is a less-invasive method of en bloc removal of gastrointestinal tract tumors. The aim of this study was to evaluate the feasibility of a grasp-and-snare EFTR technique using a novel tissue-lifting device that provides more secure tissue anchoring and manipulation. METHODS: EFTR of normal gastric tissue and model stomach tumors was performed using a double-channel therapeutic endoscope with a prototype tissue-lifting device through one channel and a prototype hexagonal snare through the other. The lifting device was advanced through the open snare and anchored to the gastric wall immediately adjacent the model tumor. The tissue-lifting device was then partially retracted into the endoscope, causing the target tissue, including tumor, to evert into the gastric lumen. The open snare was then placed distal to the tumor around uninvolved gastric tissue. Resection was performed with a blended electrosurgical current through the snare. In the live pigs, EFTR was followed by laparotomy to asses for complications. RESULTS: 24 EFTRs were performed -- 14 in explanted stomachs and 10 in live pigs. In total, 23/24 resections resulted in full-thickness gastric defects. Resection specimens measured up to 5.0 cm when stretched and pinned on a histology stage. Gross margins were negative in 17/20 model tumor resections. Two resections were complicated by gastric mural bleeding. There was no evidence of adjacent organ injury. CONCLUSIONS: EFTR of gastric tumors using the grasp-and-snare technique is feasible in pigs. This technique is advantageous in that eversion of the gastric wall avoids injury to external organs, continuous luminal insufflation is not required, and the involved techniques are familiar to endoscopists. Additional research is necessary to further evaluate safety and reliable closure.

Complete endoscopic closure of gastrotomy after natural orifice translumenal endoscopic surgery using the NDO Plicator.

BACKGROUND: The NDO Plicator is a device developed for endoscopic treatment of gastroesophageal reflux disease (GERD) by approximation of tissues together with a double-pledgeted U-stitch. It was theorized that this device may facilitate transgastric natural orifice translumenal endoscopic surgery (NOTES) because closure of the transgastric defect remains a key component for advancement of this new technology. METHODS: A standardized 12-mm gastrotomy was created endoscopically in four pigs using a combination of needle-knife cautery and balloon dilation. As the endoscope was removed, a Savary soft-tipped wire was introduced into the stomach, and the NDO Plicator was subsequently advanced over the wire. Each defect was identified, and the device was positioned. If necessary, the Plicator's tissue grasper was used to hold the superior aspect of the gastrotomy and bring the opposed borders of the defect within the jaws of the device. The device was fired three times, leaving three pledgeted suture bundles to close the gastric defect. After closure, each animal was explored, and the integrity of the closure was assessed. The animals underwent in vivo contrast fluoroscopy and ex vivo burst pressure testing studies for assessment of leakage at the closure site. RESULTS: The first animal was used to test feasibility, refine techniques, and develop a standard procedure. All of the next three animals studied showed complete sealing of the gastrotomy site without evidence of contrast extravasation on multiplanar fluoroscopic imaging. Each stomach was excised, submerged in water, and subjected to a pressurized air leak test. No leaks were noted until pressures exceeded 55 mmHg. CONCLUSION: This study supports the use of the NDO Plicator for closure of standardized gastric defects in a porcine model. In addition to closing NOTES gastrotomies, the NDO Plicator may be a particularly useful tool for obtaining complete closure of gastric perforations and anastomotic leaks, and for performing stomal reduction after gastric bypass procedures. The mechanical properties of a closure are not the only factor determining whether a leak will develop. Tissue opposition, ischemia, and tension are important factors that are not easily or reliably measured. The physiologic relevance of gastric bursting pressure is not known. Therefore, corollary animal studies with longer-term evaluation are necessary before research proceeds to clinical trials.

Diaphragm pacing with natural orifice transluminal endoscopic surgery: potential for difficult-to-wean intensive care unit patients.

BACKGROUND: Up to 50% of the patients in the intensive care unit (ICU) require mechanical ventilation, with 20% requiring the use of a ventilator for more than 7 days. More than 40% of this time is spent weaning the patient from mechanical ventilation. Failure to wean from mechanical ventilation can in part be attributable to rapid onset of diaphragm atrophy, barotrauma, posterior lobe atelectasis, and impaired hemodynamics, which are normally improved by maintaining a more natural negative chest pressure. The authors have previously shown that laparoscopic implantation of a diaphragm pacing system benefits selected patients. They now propose that an acute ventilator assist with interventional neurostimulation of the diaphragm in the ICU is feasible and could facilitate the weaning of ICU patients from mechanical ventilation. Natural orifice transluminal endoscopic surgery (NOTES) has the potential to expand the benefits of the diaphragm pacing system to this acute patient population by allowing it to be performed at the bedside similarly to insertion of the common gastrostomy tube. This study evaluates the feasibility of this approach in a porcine model. METHODS: Pigs were anesthetized, and peritoneal access with the flexible endoscope was obtained using a guidewire, needle knife cautery, and balloon dilation. The diaphragm was mapped using a novel endoscopic electrostimulation catheter to locate the motor point (where stimulation provides complete contraction of the diaphragm). An intramuscular electrode then was placed at the motor point with a percutaneous needle. The gastrotomy was managed with a gastrostomy tube. RESULTS: Four pigs were studied, and the endoscopic mapping instrument was able to map the diaphragm to identify the motor point. In one animal, a percutaneous electrode was placed into the motor point under transgastric endoscopic visualization, and the diaphragm could be paced in conjunction with mechanical ventilation. CONCLUSIONS: These animal studies demonstrate the feasibility of transgastric mapping of the diaphragm and implantation of a percutaneous electrode for therapeutic diaphragmatic stimulation.

A reliable method for monitoring intraabdominal pressure during natural orifice translumenal endoscopic surgery.

BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) provides surgical access to the peritoneal cavity without skin incisions. The NOTES procedure requires pneumoperitoneum for visualization and manipulation of abdominal organs, similar to laparoscopy. Accurate measurement of the pneumoperitoneum pressure is essential to avoid potentially deleterious effects of intraabdominal compartment syndrome. A reliable method for monitoring pneumoperitoneum pressures during NOTES has not been identified. This study evaluated several methods of monitoring intraabdominal pressures with a standard gastroscope during NOTES. METHODS: Four female pigs (25 kg) were sedated, and a single-channel gastroscope was passed transgastrically into the peritoneal cavity. Pneumoperitoneum was achieved via a pressure insufflator through a percutaneous, intraperitoneal 14-gauge catheter. Three other pressures were recorded via separate catheters. First, a 14-gauge percutaneous catheter passed intraperitoneally measured true intraabdominal pressure. Second, a 14-gauge tube attached to the endoscope was used to measure endoscope tip pressure. The third pressure transducer was connected directly to the accessory channel of the endoscope. The abdomen was insufflated to a range of pressures (10-30 mmHg), and simultaneous pressures were recorded from all three pressure sensors. RESULTS: Pressure correlation curves were developed for all animals across all intraperitoneal pressures (mean error, -4.25 to -1 mmHg). Endoscope tip pressures correlated with biopsy channel pressures (R2 = 0.99). Biopsy channel and endoscope tip pressures fit a least-squares linear model to predict actual intraabdominal pressure (R = 0.99 for both). Both scope tip and biopsy channel port pressures were strongly correlative with true intraabdominal pressures (R2 = 0.98 and R2 = 0.99, respectively). CONCLUSION: This study demonstrates that monitoring pressure through an endoscope is reliable and predictive of true intraabdominal pressure. Gastroscope pressure monitoring is a useful adjunct to NOTES. Future NOTES procedures should incorporate continuous intraabdominal pressure monitoring to avoid the potentially deleterious effects of pneumoperitoneum during NOTES. This can be achieved by the integration of pressure-monitoring capabilities into gastroscopes.

Demographic and phenotypic features of 70 families segregating Barrett's oesophagus and oesophageal adenocarcinoma.

BACKGROUND: Based on reported familial patterns, inheritance of a predisposition of developing Barrett's oesesophagus (BO) and oesophageal adenocarcinoma (OAC) likely follows an autosomal dominant model of most inherited cancer syndromes. oesophagus (BO) and oesophageal adenocarcinoma (OAC) likely follows an autosomal dominant model of most inherited cancer syndromes. AIMS: We analysed the phenotypic features of 70 familial BO/OAC families accrued for the purpose of initiating a linkage study to search for genes that contribute to susceptibility for BO/OAC. METHODS: Families with young or familial BO/OAC were recruited from participating institutions and self-referral from advertisement. RESULTS: A total of 70 families (173 affected and 784 unaffected individuals) were recruited into this study. Mean ages of diagnosis of BO and OAC among males were 50.6 and 57.4 years, respectively; among females, 52.1 and 63.5 years, respectively. The standardised incidence ratio (SIR) of cancers other than OAC or oesophagogastric junctional adenocarcinoma (OGJAC), among probands was 0.71. Seventy one percent of the pedigrees have "typical" structures with less than three affected individuals. Power calculations under realistic model assumptions suggest that if genetic heterogeneity is absent or limited, then DNA collection from members of these pedigrees could enable the identification of a novel candidate susceptibility gene for BO/OAC in a genome scan. CONCLUSIONS: This is the largest series of families with BO/OAC yet reported, features of which are consistent with inherited germline predisposition. Further, the SIR of cancers other than OAC/OGJAC was 0.71 among 70 probands, indicating these individuals were not more likely to develop non-OAC cancers.

Endoscopic ultrasonography.

Optimal treatment of gastric carcinoma requires accurate staging as there are marked differences in the prognosis of early and advanced gastric cancer which influence the decision for surgical resection versus nonsurgical palliation. Endoscopic ultrasonography (EUS), by virtue of its considerable accuracy, has become the method of choice for regional staging of gastric cancer. EUS is unique in its ability to image the gastric wall as a 5-layer structure that correlates with actual histological layers. Thus, tumor depth can be imaged very precisely. Peritumor inflammation is the most common cause for overstaging by EUS; difficulty in determining tumor involvement of, but not through, the subserosa is another important reason for inaccurate staging. EUS is able also to detect small lymph nodes in the perigastric region. Although assessment of malignancy in nodes can be difficult, ultrasound-guided fine needle aspiration cytology appears to be an accurate method to determine lymph node status. Surgery remains the standard treatment for gastric cancer, but new methods of endoscopic resection combined with high-frequency ultrasound may hold promise for future treatment of early gastric cancer. In addition to current radial and sector scanning instruments, recently introduced high-frequency ultrasound probes enhance the diagnostic possibilities of this technology.

Procedure-specific outcomes assessment for endoscopic ultrasonography.

Endosonography (EUS) is a relative newcomer to the field of gastrointestinal endoscopy. Nevertheless, two prospective studies with similar results have shown that EUS leads to a change in management in roughly two-thirds of patients in whom it is performed, with many of these changes being to less invasive or less expensive management. Preliminary investigations on the use of catheter probes for performing EUS have shown similar effects. Specific investigations on the effect of EUS on the outcomes of patients with submucosal tumors, esophageal cancers, pancreatic cancers, and rectal cancers need to be performed. Selective studies have demonstrated EUS to be cost-effective for the management of submucosal tumors and ampullary tumors. The complication rate of EUS appears to be comparable to that of upper endoscopy. There is little or no information regarding training in EUS, practice variation, or affect of EUS on quality of life.

[Stimulation of regenerative processes and correction of the functional activity of the liver in its partial resection and toxic lesions]. / Stimuliatsiia protsessov regeneratsii i korrektsiia funktsional'noi aktivnosti pecheni pri ee chastichnoi rezektsii i toksicheskikh porazheniiakh.

The effects of hepatotropic growth factors (HGFs) and phospholipid drugs on the recovery of functions and the regeneration of the rat liver were studied in CC14-induced toxic damage and after partial hepatectomy (PHE). HGFs isolated from the cytoplasmic cells of the regenerating liver, as well as from the liver of the animals given prodigiozan and from the media taken after culturing the explants of the regenerating liver were found to stimulate DNA synthesis and hepatocytic proliferation following PHE and in the cirrhotic liver. Prodigiozan was shown to induce the formation of HGFs not only in the rat liver following PHE, but in the liver of intact animals. It was established that the covalently binding complex of albumin and bilirubin stimulated the synthesis of proteins and DNA in the regenerating liver, but non-covalently binding complex inhibited these processes. When CC14 was administered to the animals, the two complexes enhanced the reparative synthesis of DNA, without changing the level of replicating synthesis, the non-covalently binding complex completely eliminating the single-strand breaks in DNA. Phospholipid agents containing soybean and sunflower phosphatidylcholines increased the synthesis of RNA and albumin, which were decreased due to exposure to CC14 and had the property of stimulating the synthesis of total DNA and considerably enhancing that of mitochondrial DNA.

[Characteristics of the reaction of the macrophage lysosomal apparatus in guinea pigs immunized with a live and a killed Br. abortus culture]. / Osobennosti reaktsii lizosomal'nogo apparata makrofagov morskikh svinok, immunizirovannykh zhivoi i ubitoi kul'turoi Br. abortus

Accumulation of fluorescent antigen-antibody complex in the cytoplasmic granules at various time intervals after the phagocytosis of brucellae treated with brucella fluorescent serum was studied in the peritoneal macrophage culture of guinea pigs immunized with live and killed brucella culture. The activity of the lysosomic system was also studied. Immunization with live brucellae led to an increase in the acid phosphatase activity, to an increased rate of destruction of phagocytosed spheroplasts with fluorescent antibodies fixed on their surface, to a more rapid accumulation of fluorescent antigen-antibody complex in secondary lysosomes and to a more marked humoral response than the immunization with the killed culture. Changes in macrophages correlated with positive skin allergic reactions, and were apparently associated with increased sensitivity of a delayed type.

[Effect of antilysosomal sera on the phagocytosis of corpuscular antigens in a macrophage culture]. / Vliianie antilizosomnykh syvorotok na fagotsitoz korpuskuliarnykh antigenov v kul'ture makrofagov

A study was made of the effect of the antilysosomal sera on various phases of phagocytosis Macrophages fluorochromized with acridine orange served as a model for the assessment of the effect of the antilysosomal sera on the phagocytosis: the fluorescent-microscopic method permitted to evaluate quantitatively the activity of the antilysosomal sera and to study the intracellular changes in the phagocytized antigen associated with its interaction with the lysosomes. The data obtained showed the antisera to the enzymes and the lysosome membranes to inhibit the phagocytosis both in the presence of a complement and without it. It was also demonstrated that the antilysosomal sera influenced the activity of the acid phosphatase and its distribution in the macrophages.

[Stimulation of DNA and RNA synthesis in the liver of hepatectomized rats by fractions of liver cytosol and conditioned media obtained during cultivation of rat liver explants]. / Stimuliatsiia sinteza DNK i RNK v pecheni gepatéktomirovannykh krys fraktsiiami tsitozolia pecheni i konditsionirovannoi sredy, poluchennoi pri kul'tivirovanii éksplantatov pecheni krys.

Heat resistant fractions stimulating proliferation (PSF) were identified in the fractions of rat liver cytosol after 70% hepatectomy as well as in the medium harvested after cultivation of rat liver explants. The PSF augmented considerably the rate of DNA synthesis, it increased synthesis and transport of rapidly labelled RNA as well as the level of mitotic activity in rat liver tissue resected by 30% and 80%. Role of the PSF in regulation and acceleration of regeneration processes in the residual parts of liver tissue, remained after hepatectomy, is discussed.