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Biomedical subjects

Sergey V Kantsevoy

Publications and source records attributed to Sergey V Kantsevoy.

15 recordsLinked to original sources

Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study.

BACKGROUND & AIMS: Individuals with a strong family history of pancreatic cancer and persons with Peutz-Jeghers syndrome (PJS) have an increased risk for pancreatic cancer. This study screened for early pancreatic neoplasia and compared the pancreatic abnormalities in high-risk individuals and control subjects. METHODS: High-risk individuals with PJS or a strong family history of pancreatic cancer were prospectively evaluated with baseline and 12-month computed tomography (CT) scan and endoscopic ultrasonography (EUS). If EUS was abnormal, EUS-fine-needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP) were performed. Surgery was offered to patients with potentially neoplastic lesions. Radiologic findings and pathologic diagnoses were compared. Patients undergoing EUS and/or ERCP for benign non-pancreatic indications were concurrently enrolled as control subjects. RESULTS: Seventy-eight high-risk patients (72 from familial pancreatic cancer kindreds, 6 PJS) and 149 control patients were studied. To date, 8 patients with pancreatic neoplasia have been confirmed by surgery or fine-needle aspiration (10% yield of screening); 6 patients had 8 benign intraductal papillary mucinous neoplasms (IPMNs), 1 had an IPMN that progressed to invasive ductal adenocarcinoma, and 1 had pancreatic intraepithelial neoplasia. EUS and CT also diagnosed 3 patients with 5 extrapancreatic neoplasms. At EUS and ERCP abnormalities suggestive of chronic pancreatitis were more common in high-risk patients than in control subjects. CONCLUSIONS: Screening EUS and CT diagnosed significant asymptomatic pancreatic and extrapancreatic neoplasms in high-risk individuals. IPMN should be considered a part of the phenotype of familial pancreatic cancer. Abnormalities suggestive of chronic pancreatitis are identified more commonly at EUS and ERCP in high-risk individuals.

Adult↗

Hypoxia-inducible factor-1alpha promotes nonhypoxia-mediated proliferation in colon cancer cells and xenografts.

Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that directly transactivates genes important for the growth and metabolism of solid tumors. HIF-1alpha is overexpressed in cancer, and its level of expression is correlated with patient mortality. Increased synthesis or stability of HIF-1alpha can be induced by hypoxia-dependent or hypoxia-independent factors. Thus, HIF-1alpha is expressed in both nonhypoxic and hypoxic cancer cells. The role of HIF-1alpha in nonhypoxia-mediated cancer cell proliferation remains speculative. We have disrupted HIF-1alpha by targeted homologous recombination in HCT116 and RKO human colon cancer cells. Loss of HIF-1alpha significantly reduced nonhypoxia-mediated cell proliferation in vitro and in vivo. Paradoxically, loss of HIF-1alpha expression did not grossly affect the hypoxic compartments within tumor xenografts in vivo, although HIF-1alpha promoted cell proliferation and survival under hypoxia in vitro. To further test the role of HIF-1alpha within tumor compartments, we generated cells with combined disruptions of both HIF-1alpha and vascular endothelial growth factor (VEGF). In all xenografts, disruption of VEGF led to marked expansion of the hypoxic compartments and growth delay. Nonetheless, the presence or absence of HIF-1alpha did not grossly affect these expanded hypoxic compartments. These data provide compelling evidence that, in a subset of colon cancers, (a) HIF-1alpha is a positive factor for nonhypoxia-mediated cell proliferation in vitro and in vivo and (b) HIF-1alpha is a positive factor for cell proliferation and survival under hypoxic conditions in vitro, but does not grossly contribute to the tumor hypoxic compartments in vivo.

Animals↗

The endoscopic transilluminator: an endoscopic device for identification of the proximal jejunum for transgastric endoscopic gastrojejunostomy.

BACKGROUND: Localization of the proximal jejunum is important for creation of gastrojejunal anastomosis to palliate gastric outlet obstruction or for treatment of obesity with gastric bypass. OBJECTIVE: To facilitate identification of the proximal jejunum during transgastric endoscopic gastrojejunostomy with the use of an endoscopic transilluminator (ET). DESIGN AND SETTING: Acute experiments in a live porcine model. INTERVENTIONS: The ET is a 3500-mm long, 6F radio-opaque tube with a fiberoptic core that lights up at its distal end. When situated in the intestinal lumen, it transilluminates the bowel wall. With the animal under general anesthesia with endotracheal intubation, a colonoscope was advanced to the proximal jejunum. A plastic tube (3500-mm long, 3.5 mm in diameter) was passed through the biopsy channel and placed into the small bowel. The colonoscope was withdrawn, leaving the tube in place. The ET was introduced into the jejunum through the tube. A gastric wall incision was made and the endoscope was advanced to the peritoneal cavity. The transilluminated loop of the proximal jejunum was identified and gastrojejunal anastomosis was made by use of a previously reported endoscopic technique. MAIN OUTCOME MEASUREMENTS: Identification of the proximal jejunum. RESULTS: Eleven pigs (average weight 55 kg) had ET placement. In all of the pigs, placement of the ET was performed easily to the proximal small bowel, and the proximal jejunum was successfully localized by either direct visualization of the transilluminated loop only or with the aid of fluoroscopy. The tip of the ET was usually located about 50 to 70 cm distal to the ligament of Treitz. There were no complications related to the use of ET. LIMITATIONS: The device has not yet been evaluated in humans. CONCLUSIONS: The ET is a safe instrument and can be used to identify the proximal jejunum to facilitate endoscopic gastrojejunostomy.

Animals↗

Immediate endoscopic closure of colon perforation by using a prototype endoscopic suturing device: feasibility and outcome in a porcine model (with video).

BACKGROUND: Perforation is an uncommon but potentially devastating complication of colonoscopy. Surgical closure is the standard of care. Immediate endoluminal closure of a perforation would avoid the morbidity and mortality associated with general anesthesia, laparotomy, and surgical repair. OBJECTIVES: To evaluate the feasibility and safety of full-thickness endoscopic closure of colonic perforations with a prototype endoscopic suturing device, the Eagle Claw, in a porcine model. DESIGN: Endoscopic animal experimental study of closure of colon perforation by using a porcine model. SUBJECTS: Ten pigs were included in the study. INTERVENTIONS: The Eagle Claw was used to close small perforations (1.5 to 2 cm) of the colon created by needle-knife with the animal under general anesthesia by using the endoluminal route. All animals received intravenous antibiotics and were allowed to eat after 24 hours. MAIN OUTCOME MEASUREMENTS: The animals were monitored daily for signs of sepsis and peritonitis. On day 7, they were euthanized. The peritoneal cavity was examined for fecal peritonitis, and the colon perforation site was checked for wound dehiscence and pericolic abscess formation. RESULTS: Endoscopic closure of the colon perforation was successful in 7 animals, and they recovered well without any sepsis or peritonitis. Necropsy did not reveal fecal peritonitis or pericolonic abscess formation at the site of perforation, and the perforation healed well. Closure was successful in 1 animal, but necropsy revealed dehiscence of the colon perforation site. Endoscopic closure was unsuccessful in 2 animals, and these were euthanized immediately. CONCLUSIONS: Closure of acute perforation of the colon is feasible with the Eagle Claw endoscopic suturing device in a porcine model.

Animals↗

Pilot study of the porcine uterine horn as an in vivo appendicitis model for development of endoscopic transgastric appendectomy.

BACKGROUND: Iatrogenic inflammation of the porcine uterine horn may serve as an in vivo appendicitis model for the development of endoscopic transgastric appendectomy. OBJECTIVE: Five female pigs. STUDY DESIGN: Animal study. SETTINGS: General anesthesia. MAIN OUTCOME MEASUREMENTS: Anatomical appearance and technical feasibility. INTERVENTIONS: Three pigs were used to identify an injectable material that would inflame the uterine horn, and 2 pigs were used for a pilot appendectomy. Three types of materials were individually injected into the bilateral uterine horns, and the ideal material to inflame the uterine horn was injected into the right uterine horn for the last 2 pigs. After 24 hours, the injected uterine horns of the first 3 pigs were assessed and a pilot appendectomy was performed in the last 2 pigs. RESULTS: Ethanolamine oleate (EO) injected uterine horns demonstrated similarities to the inflamed human appendix. Simulations of the appendectomy were successfully performed by using the EO model. LIMITATIONS: Suboptimal existing tools. CONCLUSIONS: This preliminary study demonstrated the technical feasibility to create a model for acute appendicitis by using the porcine uterine horn and transgastric appendectomy.

Animals↗

Principle and history of Natural Orifice Translumenal Endoscopic Surgery (NOTES).

The field of gastrointestinal endoscopy has been witnessing major advances over the last five decades. Developing from flexible endoscopy to endoscopic retrograde cholangiopancreatography (ERCP) in the 1950's and 70's to endoscopic ultrasound in the 80's, endoscopic technology has been transformed from serving purely diagnostic purposes to therapeutic applications. One recent major advance is the notion of using the flexible endoscope, taking it beyond the gastrointestinal lumen into what lies beyond the confines of the gastrointestinal tract. Natural orifice translumenal surgery offers the exciting potential to be safer, less invasive and possibly more cost-effective than the traditional open surgical or laparoscopic approach. The history and principles of natural orifice translumenal endoscopic surgery (NOTES), along with future implications, are outlined in this article.

Endoscopy, Digestive System↗

Peroral transgastric endoscopic ligation of fallopian tubes with long-term survival in a porcine model.

BACKGROUND: We have previously reported the feasibility and safety of the peroral transgastric endoscopic approach for diagnostic peritoneoscopy, liver biopsy, and gastrojejunostomy with long-term survival in a porcine model. This approach eliminates incisions of the abdominal wall, providing a less invasive alternative to diagnostic and therapeutic laparoscopy. We now report successful performance of peroral endoscopic transgastric ligation of Fallopian tubes with long-term survival in a porcine model. METHODS: Six female 50-kg pigs had general anesthesia and irrigation of the stomach with an antibiotic solution. Gastric puncture was performed with needleknife electrocautery followed by balloon dilatation of the tract with 20-mm TTS dilating balloon (Microvasive). A standard upper endoscope that underwent high-level disinfection and gas sterilzation was advanced into the peritoneal cavity through a sterile overtube. Both Fallopian tubes were identified and one was ligated using Olympus Endoloops. The other patent tube served as a control. Tubal patency was evaluated by hysterosalpingogram before and after ligation. After a follow-up period of 2-3 weeks, the pigs were sacrificed for postmortem examination. RESULTS: The Fallopian tubes were easily accessed, identified and ligated in all 6 pigs. In each pig, fluoroscopy confirmed complete obstruction of the ligated tube with preserved patency of the other tube. All pigs survived well and ate heartily without any ill-effects. Postmortem examination did not reveal any peritonitis or intra-abdominal adhesions. The Endoloops were in place with complete obstruction of the ligated tubes and patency of the controls. Histopathologic examination of the tubes showed chronic inflammatory infiltrates without abscesses. CONCLUSIONS: The peroral endoscopic transgastric approach to ligation of the Fallopian tubes with long-term survival is technically feasible and safe in a porcine model. The endoscopic transgastric approach to the peritoneal cavity has potential for a wide array of diagnostic and therapeutic procedures.

Animals↗

Endoscopic suturing without extracorporeal knots: a laboratory study.

BACKGROUND: To eliminate cumbersome extracorporeal knotting, we designed a new endoscopic suturing device, the Eagle Claw V. The efficacy of the new device was tested on the Erlangen model and was compared with the initial extracorporeal knotting version (Eagle Claw II). METHODS: Segments of porcine splenic arteries were placed on the mucosal surface of the anterior wall of a pig stomach. The two ends of the artery were brought out through the gastric wall and were connected to a two-channel manometer. The Eagle Claw V has a curved needle with a detachable tip. After puncturing the tissue, the needle tip was engaged into a catching cartridge, where the suture had been embedded in a tightening mechanism. The suture could be tightened by simply pulling the end. The Eagle Claw V was used to plicate the splenic arteries mounted on the stomach. Suturing was considered secure if the suture could withstand endoluminal pressure greater than 200 mm Hg that lasted at least 10 seconds. RESULTS: Eleven of 15 stitches (73.3%) gained secure plication of the vessels. The suturing time (mean +/- standard deviation 2.93 +/- 0.80 minutes) was significantly faster than that of the Eagle Claw II (9.38 +/- 1.51 minutes). The device consistently achieved penetration of the muscular layer, and 4 of 15 sutures included the serosa. The 4 failures were because of suture breakage in two, thread entanglement in one, and cartridge dislodgement in one. CONCLUSIONS: The present prototype represents significant improvements in the ease of operation and the security of the suture, bringing the technique closer to clinical use for a variety of applications.

Animals↗

Eagle Claw II: A novel endosuture device that uses a curved needle for major arterial bleeding: a bench study.

BACKGROUND: Control of bleeding from major arteries in the upper-GI tract remains difficult with currently available endoscopic devices. We designed an endosuture device that uses a curved needle and extracorporeal knotting, and assessed the device in stopping arterial bleeding in a bench model. METHODS: Harvested porcine splenic arteries (2-mm diameter) were tunneled submucosally in pig stomach with the open end protruding into an artificially created mucosal defect. The outer end of the vessel was connected to a pulsatile pump, and red ink was infused at a pressure of about 100 mm Hg. The stomach was installed on an Erlangen endo-training model. The suturing device (Eagle Claw II), mounted outside an endoscope, has an eyed, curved needle that carries a 3-0 nylon thread. After puncture, the thread was retrieved by using a hook. Three-throw square knots were tied at the thread extracorporeally and were pushed into place by using a knotting cap. The criteria of successful plication was defined as hemostasis after knotting, no leakage at pressures of >200 mm Hg, and the vessel was completely encircled by the suture. RESULTS: A total of 25 sutures were made with the mean time of 9.38 minutes (standard deviation 1.51). Control of the bleeding was obtained with 17 sutures (68%). The causes for failure were the following: a suture was too shallow (4), a loose knot (2), incorrect suture position (1), and stomach-wall edema (1). CONCLUSIONS: Control of bleeding from large arteries by using endoscopic suturing is possible. Continued refinements of the device are required.

Animals↗

Endoscopic gastrojejunostomy with survival in a porcine model.

BACKGROUND: We have previously reported the feasibility and the safety of an endoscopic transgastric approach to the peritoneal cavity in a porcine model. We now report successful performance of endoscopic gastrojejunostomy with survival. METHODS: All procedures were performed on 50-kg pigs, with the pigs under general anesthesia, in aseptic conditions with sterilized endoscopes and accessories. The stomach was irrigated with antibiotic solution, and a gastric incision was performed with a needle-knife and a sphincterotome. A standard upper endoscope was advanced through a sterile overtube into the peritoneal cavity. A loop of jejunum was identified, was retracted into the stomach, and was secured with sutures while using a prototype endoscopic suturing device. An incision was made into the jejunal loop with a needle-knife, and the filet-opened ends of the jejunal wall were secured to the gastric wall with a second line of sutures, completing the gastrojejunostomy. OBSERVATIONS: Two pigs survived for 2 weeks. Endoscopy and a radiographic contrast study performed after gastrojejunostomy revealed a patent anastomosis with normal-appearing gastric and jejunal mucosa. Postmortem examination demonstrated a well-healed anastomosis without infection or adhesions. CONCLUSIONS: The endoscopic transgastric approach to create a gastrojejunostomy is technically feasible and can be performed, with survival, in a porcine model.

Animals↗

Flexible transgastric peritoneoscopy: a novel approach to diagnostic and therapeutic interventions in the peritoneal cavity.

BACKGROUND: A novel endoscopic peroral transgastric approach to the peritoneal cavity was tested in a porcine model in acute and long-term survival experiments. METHODS: Transgastric peritoneoscopy was evaluated in 50-kg pigs. After upper endoscopy, the peritoneal cavity was accessed by needle-knife puncture of the gastric wall, followed by extension of the incision either with a pull-type sphincterotome or by balloon dilation. The peritoneal cavity was examined, and a liver biopsy specimen was obtained. The gastric wall incision was closed with clips. OBSERVATIONS: Twelve acute and 5 survival experiments were performed. Both techniques of gastric wall incision were without complication. The acute experiments demonstrated the technical feasibility of the approach. In the survival experiments, all pigs recovered and gained weight. CONCLUSIONS: The peroral transgastric approach to peritoneal cavity technically is feasible and has the potential to be an alternative to laparoscopy and laparotomy.

Animals↗

Widespread EMR: a new technique for removal of large areas of mucosa.

BACKGROUND: Widespread EMR is a novel technique for resection of large areas of mucosa as a single bloc. Large lesion size (>2 cm) is a recognized limitation of current EMR techniques. This study assessed the technical feasibility, efficacy, and safety of widespread EMR in a porcine model. METHODS: Widespread EMR was performed in 6 pigs. A submucosal fluid cushion was created in the distal esophagus by using a 0.83% solution of hydroxypropyl methylcellulose. A mucosal strip 5 cm in length and including at least 50% of the luminal circumference was marginated by using a prototype cutting device. The proximal end of the mucosa was stripped from the submucosa by using a grasping forceps. The distal end was snare resected. Resected tissue was assessed histologically. Endoscopy was repeated at weeks 1 and 6. At week 6, a second widespread EMR of the mucosa on the wall opposite the initial resection was attempted to create a full circumferential resection. RESULTS: Widespread EMR was completed in all animals. The esophagus was denuded of mucosa in 5-cm lengths that included 50% of the circumference of the lumen. No procedure-related complication was observed. Histologic assessment demonstrated that the resection specimen included mucosa and submucosa but not muscularis propria. Endoscopy at 1 week revealed mucosal regrowth in two animals and ulceration in 4. At week 6, regrowth of mucosa was noted in all animals. The second wide EMR proved to be technically difficult and was associated with perforation, peri-esophageal abscess, and stricture formation. CONCLUSIONS: Wide EMR appears to be technically feasible for removal of large areas of mucosa. Mucosal strips 5 cm long that included over 50% of the luminal circumference were resected safely. Resection was followed by complete regrowth of the mucosa. However, a second wide EMR to create a circumferential resection proved to be technically difficult and unsafe.

Animals↗

Endoscopic cryotherapy for the treatment of bleeding mucosal vascular lesions of the GI tract: a pilot study.

BACKGROUND: Thermal therapy is the cornerstone of endoscopic treatment of bleeding mucosal lesions of the GI tract. However, there is a 20% failure rate and contact devices may be cumbersome in the treatment of large bleeding areas. A pilot study was conducted to evaluate the safety and efficacy of endoscopic cryotherapy for bleeding mucosal vascular lesions. METHODS: Patients with recurrent bleeding from diffuse mucosal vascular lesions were treated with cryotherapy and had endoscopic and clinical follow-up. RESULTS: Twenty-six patients with gastric and duodenal arteriovenous malformations (n = 7), watermelon stomach (n = 7), radiation-induced gastritis (n = 5), and radiation-induced proctitis (n = 7) were treated with mean of 3.4 (1.6) sessions. The best results were achieved in patients with radiation-induced proctitis, with cessation of bleeding in all 7 patients. Cryotherapy was also effective in patients with multiple arteriovenous malformations (86%) and watermelon stomach (71%). It was less effective in patients with radiation-induced damage to stomach and duodenum, although all patients in this group were debilitated because of disseminated malignancy. CONCLUSIONS: Cryotherapy is a safe and effective treatment for bleeding from diffuse mucosal lesions of the GI tract. Bleeding from radiation-induced proctitis and multiple arteriovenous malformations is particularly responsive to endoscopic cryotherapy.

Aged↗