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1.
Am J Physiol Gastrointest Liver Physiol ; 294(2): G554-66, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18079280

ABSTRACT

Based on findings in rodents, we sought to test the hypothesis that purinergic modulation of synaptic transmission occurs in the human intestine. Time series analysis of intraneuronal free Ca(2+) levels in submucosal plexus (SMP) from Roux-en-Y specimens was done using Zeiss LSM laser-scanning confocal fluo-4 AM Ca(2+) imaging. A 3-s fiber tract stimulation (FTS) was used to elicit a synaptic Ca(2+) response. Short-circuit current (I(sc) = chloride secretion) was recorded in mucosa-SMP in flux chambers. A distension reflex or electrical field stimulation was used to study I(sc) responses. Ca(2+) imaging was done in 1,222 neurons responding to high-K(+) depolarization from 61 surgical cases. FTS evoked synaptic Ca(2+) responses in 62% of recorded neurons. FTS caused frequency-dependent Ca(2+) responses (0.1-100 Hz). FTS Ca(2+) responses were inhibited by Omega-conotoxin (70%), hexamethonium (50%), TTX, high Mg(2+)/low Ca(2+) (< or = 100%), or capsaicin (25%). A P2Y(1) receptor (P2Y(1)R) antagonist, MRS-2179 or PLC inhibitor U-73122, blocked FTS responses (75-90%). P2Y(1)R-immunoreactivity occurred in 39% of vasoactive intestinal peptide-positive neurons. The selective adenosine A(3) receptor (AdoA(3)R) agonist 2-chloro-N(6)-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide (2-Cl-IBMECA) caused concentration- and frequency-dependent inhibition of FTS Ca(2+) responses (IC(50) = 8.5 x 10(-8) M). The AdoA(3)R antagonist MRS-1220 augmented such Ca(2+) responses; 2-Cl-IBMECA competed with MRS-1220. Knockdown of AdoA(1)R with 8-cyclopentyl-3-N-(3-{[3-(4-fluorosulphonyl)benzoyl]-oxy}-propyl)-1-N-propyl-xanthine did not prevent 2-Cl-IBMECA effects. MRS-1220 caused 31% augmentation of TTX-sensitive distension I(sc) responses. The SMP from Roux-en-Y patients is a suitable model to study synaptic transmission in human enteric nervous system (huENS). The P2Y(1)/Galphaq/PLC/inositol 1,3,5-trisphosphate/Ca(2+) signaling pathway, N-type Ca(2+) channels, nicotinic receptors, and extrinsic nerves contribute to neurotransmission in huENS. Inhibitory AdoA(3)R inhibit nucleotide or cholinergic transmission in the huENS.


Subject(s)
Enteric Nervous System/physiology , Receptors, Purinergic/physiology , Synaptic Transmission/physiology , Aniline Compounds , Calcium/metabolism , Chloride Channels/drug effects , Chloride Channels/metabolism , Electric Stimulation , Enteric Nervous System/drug effects , Fluorescent Dyes , Humans , Microscopy, Confocal , Nerve Fibers/physiology , Neurons/drug effects , Neurons/metabolism , Obesity/metabolism , Quinazolines/pharmacology , Receptors, Purinergic/drug effects , Receptors, Purinergic P2/physiology , Receptors, Purinergic P2Y1 , Submucous Plexus/cytology , Submucous Plexus/drug effects , Submucous Plexus/physiology , Synaptic Transmission/drug effects , Triazoles/pharmacology , Type C Phospholipases/metabolism , Vasoactive Intestinal Peptide/metabolism , Xanthenes
2.
Surg Endosc ; 21(7): 1180-3, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17287911

ABSTRACT

BACKGROUND: Few Western studies have focused on percutaneous techniques using percutaneous transhepatic choledochoscopy (PTHC) and holmium:yttrium-aluminum-garnet (YAG) laser to ablate biliary calculi in patients unable or unwilling to undergo endoscopic or surgical removal of the calculi. The authors report the efficacy of the holmium:YAG laser in clearing complex biliary calculi using percutaneous access techniques. METHODS: This study retrospectively reviewed 13 non-Asian patients with complex secondary biliary calculi treated percutaneously using holmium:YAG laser. Percutaneous access was accomplished via left, right, or bilateral hepatic ducts and upsized for passage of a 7-Fr video choledochoscope. Lithotripsy was performed under choledochoscopic vision using a holmium:YAG laser with 200- or 365-microm fibers generating 0.6 to 1.0 joules at 8 to 15 Hz. Patients underwent treatment until stone clearance was confirmed by PTHC. Downsizing and subsequent removal of percutaneous catheters completed the treatment course. RESULTS: Seven men and six women with an average age of 69 years underwent treatment. All the patients had their biliary tract stones cleared successfully. Of the 13 patients, 3 were treated solely as outpatients. The average length of percutaneous access was 108 days. At this writing, one patient still has a catheter in place. The average number of holmium:YAG laser treatments required for stone clearance was 1.6, with no patients requiring more than 3 treatments. Of the 13 patients, 8 underwent a single holmium:YAG laser treatment to clear their calculi. Prior unsuccessful attempts at endoscopic removal of the calculi had been experienced by 7 of the 13 patients. Five patients underwent percutaneous access and subsequent stone removal as their sole therapy for biliary stones. Five patients were cleared of their calculi after percutaneous laser ablation of large stones and percutaneous basket retrieval of the remaining stone fragments. There was one complication of pain requiring admission, and no deaths. CONCLUSIONS: The use of PTHC with holmium:YAG laser ablation is safe and efficacious, but requires prolonged biliary access and often multiple procedures to ensure clearance of all calculi.


Subject(s)
Aluminum , Gallstones/therapy , Lithotripsy, Laser/methods , Yttrium , Adult , Aged , Cholangiopancreatography, Endoscopic Retrograde/methods , Female , Follow-Up Studies , Gallstones/diagnostic imaging , Humans , Length of Stay , Lithotripsy, Laser/instrumentation , Male , Middle Aged , Pain Measurement , Retrospective Studies , Risk Factors , Severity of Illness Index , Treatment Outcome
3.
Surg Endosc ; 21(3): 445-8, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17054006

ABSTRACT

BACKGROUND: As with new laparoscopic techniques, the ability to convince surgeons and gastroenterologists to embrace endolumenal techniques and the additional training required to perform the new procedures will correlate with how rapidly endolumenal therapies are adopted. The authors measured their ability to change attitudes among surgeons, who may or may not perform endoscopy as a part of their practice, toward endolumenal therapies. METHODS: As part of the endoluminal therapy postgraduate course presented at the annual Society of American Gastrointestinal Endoscopic Surgeons (SAGES) meeting in Ft. Lauderdale, Florida 2005, experts presented current literature and data on new endolumenal techniques. The participants, primarily of surgeons, were polled electronically about a number of case scenarios before and after their presentation. Each scenario was relevant to the topic presented and chosen to reflect potentially controversial disease processes with traditional or endolumenal treatment options. The responses were collected in real time and displayed to course participants. RESULTS: A panel of 10 experts presented data on a range of endolumenal therapies including endolumenal treatment for gastroesophageal reflux disease (GERD), endoscopic stenting, endoscopic treatments in bariatric surgery, intraoperative endoscopy, endoscopic mucosal resection (EMR), transanal endoscopic microsurgery (TEM), mucosal ablation for Barrett's esophagus, intralumenal resection, translumenal endoscopic surgery, and how to educate surgeons in new endolumenal techniques. Demographic data showed that 83.6% of the participants performed endoscopy as part of their practice. A comparison with traditional surgical options showed a statistically significant positive attitude change (p < 0.05) toward adoption of most endolumenal techniques after expert presentation. Only EMR and TEM did not show a statistically significant change in the participants' willingness to adopt these techniques. There was no significant change in the attitudes of how best to train surgeons. After presentation of the training options, 76% of the respondents believed that these techniques should be taught in residency. CONCLUSIONS: The education of surgeons in new endolumenal therapeutic techniques can have a significant impact in terms of changing practice attitudes and may accelerate adoption of new endoscopic techniques.


Subject(s)
Angioplasty/education , Education, Medical, Continuing/methods , Gastrointestinal Diseases/surgery , Health Knowledge, Attitudes, Practice , Angioplasty/instrumentation , Bariatrics/methods , Curriculum , Endoscopes, Gastrointestinal , Endoscopy, Gastrointestinal/methods , Humans , Laparoscopy , Microsurgery , Practice Patterns, Physicians'/statistics & numerical data , United States
4.
Surg Endosc ; 21(4): 560-9, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17180281

ABSTRACT

BACKGROUND: This study aimed to determine the optimal treatment parameters for the ablation of intestinal metaplasia (IM) containing high-grade dysplasia (HGD) using a balloon-based ablation system for patients undergoing esophagectomy. METHODS: Immediately before esophagectomy, patients underwent ablation of circumferential segments of the esophagus containing IM-HGD using the HALO360 system. The treatment settings were randomized to 10, 12, or 14 J/cm2 for two, three, or four applications. After esophagectomy, multiple sections from ablation zones were microscopically evaluated. Histologic end points included maximum ablation depth (histologic layer) and complete ablation of all IM-HGD (yes/no). RESULTS: Eight men with a mean age of 57 years (range, 45-71 years) were treated, and 10 treatment zones were created. There were no device-related adverse events. At resection, there was no evidence of a transmural thermal effect. Grossly, ablation zones were clearly demarcated sections of ablated epithelium. The maximum ablation depth was the lamina propria or muscularis mucosae. The highest energy (14 J/cm2, 4 applications) incurred edema in the superficial submucosa, but no submucosa ablation. Complete ablation of IM and HGD occurred in 9 of 10 ablation zones (90%), defined as complete removal of the epithelium with only small foci of "ghost cells" representing nonviable, ablated IM-HGD and demonstrating loss of nuclei and cytoarchitectural derangement. One focal area of viable IM-HGD remained at the margin of one ablation zone (12 J/cm2, 2 applications) because of incomplete overlap. CONCLUSION: Complete ablation of IM-HGD without ablation of submucosa is possible using the HALO360 system. Ablation depth is dose related and limited to the muscularis mucosae. In one patient, small residual foci of IM-HGD at the edge of the ablation zone were attributable to incomplete overlap, which can be avoided. This study, together with nonesophagectomy IM-HGD trials currently underway, will identify the optimal treatment parameters for IM-HGD patients who would otherwise undergo esophagectomy or photodynamic therapy.


Subject(s)
Barrett Esophagus/pathology , Barrett Esophagus/surgery , Catheter Ablation/instrumentation , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophagectomy/instrumentation , Aged , Barrett Esophagus/mortality , Biopsy, Needle , Catheterization/instrumentation , Equipment Design , Equipment Safety , Esophageal Neoplasms/mortality , Esophagectomy/methods , Follow-Up Studies , Humans , Immunohistochemistry , Male , Metaplasia/pathology , Middle Aged , Neoplasm Invasiveness/pathology , Risk Assessment , Survival Analysis , Treatment Outcome
5.
Surg Endosc ; 20(1): 125-30, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16333533

ABSTRACT

BACKGROUND: The goal of this study was to determine the optimal treatment parameters for the ablation of human esophageal epithelium using a balloon-based bipolar radiofrequency (RF) energy electrode. METHODS: Immediately prior to esophagectomy, subjects underwent esophagoscopy and ablation of two separate, 3-cm long, circumferential segments of non-tumor-bearing esophageal epithelium using a balloon-based bipolar RF energy electrode (BARRX Medical, Inc., Sunnyvale, CA, USA). Subjects were randomized to one of three energy density groups: 8, 10, or 12 J/cm2. RF energy was applied one time (1x) proximally and two times (2x) distally. Following resection, sections from each ablation zone were evaluated using H&E and diaphorase. Histological endpoints were complete epithelial ablation (yes/no), maximum ablation depth, and residual ablation thickness after tissue slough. Outcomes were compared according to energy density group and 1x vs 2x treatment. RESULTS: Thirteen male subjects (age, 49-85 years) with esophageal adenocarcinoma underwent the ablation procedure followed by total esophagectomy. Complete epithelial removal occurred in the following zones: 10 J/cm2 (2x) and 12 J/cm2 (1x and 2x). The maximum depth of injury was the muscularis mucosae: 10 and 12 J/cm2 (both 2x). A second treatment (2x) did not significantly increase the depth of injury. Maximum thickness of residual ablation after tissue slough was only 35 microm. CONCLUSIONS: Complete removal of the esophageal epithelium without injury to the submucosa or muscularis propria is possible using this balloon-based RF electrode at 10 J/cm2 (2x) or 12 J/cm2 (1x or 2x). A second application (2x) does not significantly increase ablation depth. These data have been used to select the appropriate settings for treating intestinal metaplasia in trials currently under way.


Subject(s)
Adenocarcinoma/surgery , Catheter Ablation/instrumentation , Esophageal Neoplasms/surgery , Esophagectomy/methods , Esophagus/surgery , Aged , Aged, 80 and over , Electrodes , Epithelium/surgery , Equipment Design , Esophagoscopy , Esophagus/pathology , Humans , Male , Middle Aged , Postoperative Period , Reoperation , Treatment Outcome
6.
Surg Endosc ; 20(1): 153-8, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16333546

ABSTRACT

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum usually is created by a compressed gas source. This exposes the patient to cool dry gas delivered at room temperature (21 degrees C) with 0% relative humidity. Various delivery methods are available for humidifying and heating CO2 gas. This study was designed to determine the effects of heating and humidifying gas for the intraabdominal environment. METHODS: For this study, 44 patients undergoing laparoscopic Roux-en-Y gastric bypass were randomly assigned to one of four arms in a prospective, randomized, single-blinded fashion: raw CO2 (group 1), heated CO2 (group 2), humidified CO2 (group 3), and heated and humidified CO2 (group 4). A commercially available CO2 heater-humidifier was used. Core temperatures, intraabdominal humidity, perioperative data, and postoperative outcomes were monitored. Peritoneal biopsies were taken in each group at the beginning and end of the case. Biopsies were subjected staining protocols designed to identify structural damage and macrophage activity. Postoperative narcotic use, pain scale scores, recovery room time, and length of hospital stay were recorded. One-way analysis of variance (ANOVA) and the nonparametric Kruskal-Wallis test were used to compare the groups. RESULTS: Demographics, volume of CO2 used, intraabdominal humidity, bladder temperatures, lens fogging, and operative times were not significantly different between the groups. Core temperatures were stable, and intraabdominal humidity measurements approached 100% for all the patients over the entire procedure. Total narcotic dosage and pain scale scores were not statistically different. Recovery room times and length of hospital stay were similar in all the groups. Only one biopsy in the heated-humidified group showed an increase in macrophage activity. CONCLUSIONS: The intraabdominal environment in terms of temperature and humidity was similar in all the groups. There was no significant difference in the intraoperative body temperatures or the postoperative variable measured. No histologic changes were identified. Heating or humidifying of CO2 is not justified for patients undergoing laparoscopic bariatric surgery.


Subject(s)
Carbon Dioxide , Gastric Bypass , Hot Temperature , Humidity , Pneumoperitoneum, Artificial , Abdomen , Adult , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/therapeutic use , Body Temperature , Dose-Response Relationship, Drug , Humans , Length of Stay , Middle Aged , Morphine/administration & dosage , Morphine/therapeutic use , Pain Measurement , Peritoneum/pathology , Recovery Room , Single-Blind Method , Time Factors
7.
Minerva Gastroenterol Dietol ; 50(3): 253-60, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15729200

ABSTRACT

Robotic surgical systems are relatively new technical devices designed to address several of the limitations inherent to standard laparoscopy. Since the 1(st) report of a computer-assisted fundoplication in 1997, numerous authors have reported their experiences with these devices in antireflux surgery. While there are several advantages to robotic when compared to standard laparoscopic antireflux surgery, there are also some distinct drawbacks. Robotic surgical systems allow the surgeon to perform more complex maneuvers with increased precision and accuracy, and without tremor. The image is high-definition and the surgeon operates in a more ergonomic position. These systems are also costly to purchase and maintain, they are large and may limit access to the patient during surgery, they provide a narrower field of view of the operative site, and they provide the surgeon with essentially no tactile feedback. Clinical outcomes of robotic fundoplication seem to be very similar to those of standard laparoscopic fundoplication, although the operating times in many series are increased when using the robot. The role of computer-assisted fundoplication in general practice, at least at the current level of robotic technology, remains to be defined.


Subject(s)
Gastroesophageal Reflux/surgery , Robotics , Surgery, Computer-Assisted , Humans , Robotics/methods , Surgery, Computer-Assisted/methods
8.
Surg Endosc ; 18(1): 56-9, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14625732

ABSTRACT

BACKGROUND: In the United States, Roux-en-Y gastric bypass has evolved into the procedure of choice for clinically severe obesity. Stomal stenosis resulting in gastric outlet obstruction is a recognized complication. Endoscopic balloon dilation is often used to treat this condition. To evaluate the safety and efficacy of endoscopic management of stomal stenosis we evaluated our treatment methods and outcomes. METHODS: The records of all patients undergoing Roux-en-Y gastric bypass from 1 July 2000 to 30 June 2002 were studied. Stenosis was defined as signs and symptoms of obstruction with inability to cannulate the gastrojejunostomy using an 8.5-mm diagnostic endoscope. Charts were reviewed and demographic data, operative course, symptoms, and outcomes were recorded. RESULTS: A total of 562 patients underwent Roux-en-Y gastric bypass for obesity during the study period. Of these, 38 patients underwent endoscopic balloon dilation for stomal stenosis, for a stenosis rate of 6.8%. The average time from surgery to initial dilation was 7.7 weeks (range 3 to 24). The average number of dilations required was 2.1 (range one to six). The mean initial balloon size was 13 mm and the mean final balloon size was 16 mm. Two patients failed endoscopic dilation and proceeded to surgery, including one patient who developed pneumomediastinum and pneumothorax after dilation. All patients were relieved of their gastric outlet obstruction. The success rate for endoscopic balloon dilation was 95% with a 3% complication rate. CONCLUSIONS: In our experience, the rate of gastrojejunostomy stenosis following Roux-en-Y gastric bypass is 6.8%. Endoscopic balloon dilation is a safe and effective therapy for stomal stenosis with a high success rate. It should be considered an appropriate intervention with a low risk for reoperation.


Subject(s)
Anastomosis, Roux-en-Y , Catheterization , Endoscopy/methods , Gastric Bypass , Gastric Outlet Obstruction/surgery , Postoperative Complications/surgery , Surgical Stomas , Adult , Constriction, Pathologic/surgery , Female , Gastric Outlet Obstruction/etiology , Humans , Male , Postoperative Complications/etiology , Retrospective Studies , Safety , Treatment Outcome
9.
Surg Endosc ; 17(10): 1521-4, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12915974

ABSTRACT

BACKGROUND: The Academic Robotics Group prospectively studied 211 robotically assisted operations to assess the safety and utility of robotically assisted surgery. METHODS: All operations took place at one of four member institutions between June 2000 and June 2001 using the recently FDA-approved daVinci robotic system. A variety of procedures were undertaken, including antireflux surgery (69), cholecystectomy (36), Heller myotomy (26), bowel resection (17), donor nephrectomy (15), left internal mammery artery mobilization (14), gastric bypass (seven), splenectomy (seven), adrenalectomy (six), exploratory laparoscopy (three), pyloroplasty (four), gastrojejunostomy (two), distal pancreatectomy (one), duodenal polypectomy (one), esophagectomy (one), gastric mass resection (one), and lysis of adhesions (one). RESULTS: Average operating room time was 188 min (range 45 to 387, SD = 83), surgical time 143 min (range 35 to 462, SD = 63), and robot time 90 min (range 12 to 235, SD = 47). Median length of stay was 1 day (range 0 to 37). There were 8 (4%) technical complications during procedures, five minor (four hook cautery dislodgement, one slipped robotic trocar) and three major (system malfunctions, two of which required conversion to standard laparoscopy). In all cases, technical problems caused only delay, without apparent altered outcome. There were medical/surgical complications in nine patients (4%). Six (3%) were considered major, including one death unrelated to the robotic procedure. CONCLUSIONS: The results of robotic-assisted surgery compare favorably with those of conventional laparoscopy with respect to mortality, complications, and length of stay. Robotic-assisted surgery is safe and effective and is a new reality for American surgery. The role of these devices in surgery will expand as the technology evolves.


Subject(s)
Digestive System Surgical Procedures/statistics & numerical data , Robotics , Surgery, Computer-Assisted/classification , Surgery, Computer-Assisted/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Nephrectomy/statistics & numerical data , Postoperative Complications/epidemiology , Prospective Studies , Surgery, Computer-Assisted/instrumentation , Treatment Outcome , United States
10.
J Laparoendosc Adv Surg Tech A ; 13(1): 33-6, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12676019

ABSTRACT

Computer-assisted surgical devices, or "surgical robots," have recently been approved for general surgical use. The device allows the surgeon remote control of multi-articulated instrument arms with a three-dimensional view. Here we report the first known case of pancreatic resection with use of a computer-assisted, or robotic, surgical device. A 46-year old woman presented with back pain and a complex cystic mass in the tail of the pancreas. The daVinci surgical robot was used to remove the lesion en bloc with the tail of the pancreas and spleen. The patient did well and returned to full activity promptly. In summary, robotic technology may enhance advanced laparoscopic procedures. Pancreatic resection is feasible, and future experience will determine the true benefits of this technique.


Subject(s)
Carcinoma, Neuroendocrine/surgery , Pancreatic Neoplasms/surgery , Robotics , Surgery, Computer-Assisted , Female , Humans , Middle Aged
11.
Surg Endosc ; 16(12): 1790-2, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12239646

ABSTRACT

BACKGROUND: A new type of computer-enhanced telemanipulator device for "robotic" laparoscopic surgery was recently approved. We prospectively evaluated the initial patients undergoing procedures with this new device at our institution. METHODS: Patient demographics, operative indications, port placement, operative time, robot time, complications, and hospital stay were recorded. Follow-up evaluation was appropriate for the individual procedure. RESULTS: Initially, 35 cases were managed. There were 22 anti-reflux procedures, 9 Heller myotomies, 1 pyloroplasty, 1 distal pancreatectomy with splenectomy, 1 esophagectomy with intrathoracic anastomosis, and 1 diagnostic laparoscopy. The operative times ranged from 88 to 458 min. The robot use times were between 16 and 185 min. There were no device-related complications. CONCLUSIONS: Computer-enhanced robotic telesurgery is a safe and effective treatment method for a variety of diseases of the proximal gastrointestinal tract. Further study is needed to determine the benefits of this approach as compared with current technology.


Subject(s)
Laparoscopy/methods , Robotics , Surgery, Computer-Assisted/methods , Surgical Procedures, Operative/methods , Telemedicine/methods , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Cholecystitis/diagnosis , Cholecystitis/surgery , Esophageal Achalasia/surgery , Esophagectomy/adverse effects , Esophagectomy/methods , Esophagogastric Junction/surgery , Follow-Up Studies , Fundoplication/adverse effects , Fundoplication/methods , Gangrene/diagnosis , Gangrene/surgery , Humans , Intraoperative Complications , Laparoscopy/adverse effects , Pancreatectomy/adverse effects , Pancreatectomy/methods , Prospective Studies , Pylorus/surgery , Splenectomy/adverse effects , Splenectomy/methods , Surgical Procedures, Operative/adverse effects , Time Factors
12.
Gene ; 278(1-2): 235-43, 2001 Oct 31.
Article in English | MEDLINE | ID: mdl-11707341

ABSTRACT

Previous studies have shown that the p16(INK4a) tumor suppressor gene is inactivated in up to 98% of human pancreatic cancer specimens and 83% of oral squamous cell carcinomas. Inactivation of the related p15(INK4b) gene has also been identified in a number of tumors and cell lines, however, its role as an independent tumor suppressor remains to be elucidated. Chemically-induced tumors in the Syrian Golden hamster (Mesocricetus auratus) have been shown to be excellent representative models for the comparative development and progression of a number of human malignancies. The purpose of this study was to determine the importance of the p16(INK4a) and p15(INK4b) genes in two experimental hamster models for human pancreatic and oral carcinogenesis. First, hamster p16(INK4a) and p15(INK4b) cDNAs were cloned and sequenced. The hamster p16(INK4a) cDNA open reading frame (ORF) shares 78%, 80%, and 81% identity with the human, mouse, and rat p16(INK4a) sequences, respectively. Similarly, the hamster p15(INK4b) cDNA ORF shares 82% and 89% sequence identity with human and mouse p15(INK4b), respectively. Second, a deletion analysis of hamster p16(INK4a) and p15(INK4b) genes was performed for several tumorigenic and non-tumorigenic hamster cell lines and revealed that both p16(INK4a) and p15(INK4b) were homozygously deleted in a cheek pouch carcinoma cell line (HCPC) and two pancreatic adenocarcinoma cell lines (KL5B, H2T), but not in tissue matched, non-tumorigenic cheek pouch (POT2) or pancreatic (KL5N) cell lines. These data strongly suggest that homozygous deletion of the p16(INK4a) and p15(INK4b) genes plays a prominent role in hamster pancreatic and oral tumorigenesis, as has been well established in correlative studies in comparable human tumors. Furthermore, this study supports the comparative importance of the hamster pancreatic and cheek pouch models of carcinogenesis in subsequent mechanistic-, therapeutic-, and preventive-based studies aimed at providing important translational data applicable to pancreatic adenocarcinoma and oral squamous cell carcinoma in humans.


Subject(s)
Cell Cycle Proteins/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , DNA, Complementary/genetics , Gene Deletion , Mesocricetus/genetics , Neoplasms, Experimental/genetics , Tumor Suppressor Proteins , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , Cricetinae , Cyclin-Dependent Kinase Inhibitor p15 , DNA Mutational Analysis , DNA, Complementary/chemistry , Homozygote , Molecular Sequence Data , Mouth Neoplasms/genetics , Mouth Neoplasms/pathology , Neoplasms, Experimental/pathology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Sequence Alignment , Sequence Analysis, DNA , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Tumor Cells, Cultured
13.
J Laparoendosc Adv Surg Tech A ; 11(4): 251-3, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11569517

ABSTRACT

PURPOSE: Our objective was to determine the efficacy of computer-assisted robotic laparoscopic Heller myotomy. METHODS: A 76-year-old woman with a significant history of achalasia was evaluated for laparoscopic Heller myotomy. The daVinci surgical system was used throughout the procedure. RESULTS: Computer assistance allowed scaling of hand motions from a range of 2:1 to 5:1. Successful dissection of the esophageal musculature was accomplished, and a Toupet-type fundoplication was performed. The patient was discharged from the hospital the day after surgery with five port incisions, each <1 cm. CONCLUSIONS: Telemanipulator computer-assisted surgical devices may have applications in procedures that require advanced and finely tuned motions, such as Heller myotomy. The benefits of extra magnification and three-dimensional imaging can help prevent esophageal perforation and identify residual circular muscle fibers.


Subject(s)
Digestive System Surgical Procedures/methods , Esophageal Achalasia/surgery , Fundoplication/methods , Laparoscopy/methods , Surgery, Computer-Assisted/methods , Aged , Digestive System Surgical Procedures/instrumentation , Esophageal Achalasia/diagnosis , Female , Humans , Robotics
14.
Arch Surg ; 136(7): 752-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11448384

ABSTRACT

HYPOTHESIS: Changing category 1 criteria to include primarily physiologic and anatomic indicators of injury, eliminating mechanism of injury criteria, decreases the rate of overtriage without compromising outcomes. METHODS: Retrospective review of our American College of Surgeons-verified level I trauma registry from January 1, 1996, to December 31, 1998, comparing patients before and after trauma alert criteria changes. RESULTS: There was a significant decrease in category 1 alerts, representing a reduction in overtriage. There was a concomitant increase in injury severity and mortality in category 1 patients. There was no significant change in injury severity or mortality for category 2 patients. CONCLUSIONS: There was a significant reduction in overtriage of trauma patients demonstrated without an appreciable impact on patient outcome. Changing trauma response criteria to more physiologic and anatomic indicators allowed improved triage of trauma patients, which improves resource allocation.


Subject(s)
Triage/standards , Wounds and Injuries/diagnosis , Adult , Female , Humans , Injury Severity Score , Male , Ohio/epidemiology , Retrospective Studies , Treatment Outcome , Triage/methods , Wounds and Injuries/mortality , Wounds and Injuries/therapy
15.
Surg Laparosc Endosc Percutan Tech ; 11(2): 88-91, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11330390

ABSTRACT

To determine the accuracy of ultrasound-diagnosed polypoid lesions of the gallbladder in their institution, the authors reviewed the records of 41 patients with polypoid lesions of the gallbladder who underwent cholecystectomy, and collected data concerning age, sex, symptoms, and histopathologic diagnosis. Histopathologic evaluation confirmed polyps in only two patients (4.9%) categorized as having polypoid lesions of the gallbladder. Most specimens from patients with ultrasonography reports suggesting small polyps manifested cholesterolosis (17 of 41) or cholelithiasis (15 of 41). No specimen harbored malignancy. Mean patient age was 47.4 years, and the most common symptoms were pain (85%), nausea (44%), vomiting (29%), and abnormal liver function test results (14%). The accuracy of sonography for diagnosing polypoid lesions of the gallbladder was poor. Many of the small polyps seen on sonography most likely represented a stone embedded in the gallbladder wall or other abnormality. Because of the likelihood of cholelithiasis, the authors recommend that patients with biliary symptoms and ultrasonography findings suggesting polypoid lesions of the gallbladder undergo cholecystectomy.


Subject(s)
Gallbladder Neoplasms/diagnostic imaging , Polyps/diagnostic imaging , Adult , Aged , Cholelithiasis/diagnostic imaging , Cholesterol/analysis , Female , Gallbladder Neoplasms/chemistry , Humans , Male , Middle Aged , Polyps/chemistry , Predictive Value of Tests , Retrospective Studies , Ultrasonography
16.
Ann Diagn Pathol ; 4(2): 95-8, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10760323

ABSTRACT

Laparoscopic and thoracoscopic autopsies have previously only been performed on an experimental basis to determine their potential usefulness as a substitute for a conventional postmortem examination. We present the case of a patient with an unusual variant of malignant melanoma (diffuse melanosis) in whom the immediate cause of death clinically was thought to be fulminant hepatic failure, the etiology of which was unknown. The family was unwilling to consent to a conventional autopsy, but would permit a postmortem examination limited to a 2-cm abdominal incision and removal of a sample of liver. In view of the unanswered clinical questions regarding the cause of the acute hepatic failure and its possible relationship to the diagnosis of diffuse melanosis, we decided that more extensive examination of the abdominal cavity, specifically the liver, was required and that the only way that this could be accomplished was by laparoscopic techniques. Laparoscopic examination of the abdominal cavity revealed multiple melanotic nodules on the surface of the liver and studding the omentum. Multiple liver samples were easily obtained; these revealed massive diffuse necrosis of the liver parenchyma with scattered nodular deposits of dark pigment consistent with melanin. We report the first known case in which a laparoscopic autopsy was used to obtain valuable information that answered clinically relevant questions. Laparoscopic autopsy can offer the a family that is unwilling to consent to a conventional postmortem examination an alternative that can potentially provide answers to clinical questions that otherwise would have been unresolved.


Subject(s)
Autopsy/methods , Melanoma/pathology , Adult , Humans , Laparoscopy/methods , Male , Melanosis/pathology
17.
Surg Endosc ; 13(12): 1208-10, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10594267

ABSTRACT

BACKGROUND: Recent data suggest that children have a higher incidence of recurrence than adults after nonoperative treatment of primary spontaneous pneumothorax (PSP). Video-assisted thoracoscopic surgery (VATS) allows efficacious therapy with significantly less morbidity. We attempt to define the most cost-effective clinically efficacious strategy using VATS to manage pediatric PSP. METHODS: We retrospectively reviewed all admissions to a tertiary care children's hospital for PSP between January 1, 1991 and June 30, 1996. RESULTS: Fifteen children had 29 primary or recurrent PSPs. Mean patient age was 14.8 +/- 1.1 years, boy-girl ratio 4:1, median body mass index 18 (normal, 20-25), and 67% of pneumothoraces left sided. All patients were managed initially nonoperatively: 14 with tube thoracostomy drainage and 1 with oxygen alone. Of the children initially managed nonoperatively, 57% had a recurrent pneumothorax, and 50% of these patients eventually developed contralateral pneumothoraces. Nonoperative treatment for recurrence resulted in a 75% second recurrence rate. In contrast, eight children who underwent operative management had a 9% incidence of recurrence. The total for charges accrued in treating 29 pneumothoraces in these 15 patients was approximately $315,000. In the same population, the estimated charges for initial nonoperative therapy followed by bilateral thoracoscopy after a single recurrence would be $230,000. CONCLUSIONS: A cost-effective treatment strategy for pediatric primary spontaneous pneumothorax is tube thoracostomy at first presentation, followed by VATS with thoracoscopic bleb resection and pleurodesis for patients who experience recurrent pneumothorax.


Subject(s)
Pneumothorax/economics , Pneumothorax/surgery , Thoracic Surgery, Video-Assisted/economics , Adolescent , Adult , Cost-Benefit Analysis , Drainage , Hospital Charges , Humans , Pneumothorax/therapy , Recurrence , Retrospective Studies , Thoracostomy/economics
18.
Am J Surg ; 178(5): 415-7, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10612540

ABSTRACT

BACKGROUND: Video broadcasting of surgical procedures is an important tool for education, training, and consultation. Current video conferencing systems are expensive and time-consuming and require preplanning. Real-time Internet video is known for its poor quality and relies on the equipment and the speed of the connection. The Internet2, a new high-speed (up to 2,048 Mbps), large bandwidth data network presently connects more than 100 universities and corporations. We have successfully used the Internet2 to broadcast the first real-time, high-quality audio/video program from a live laparoscopic operation to distant points. METHODS: Video output of the laparoscopic camera and audio from a wireless microphone were broadcast to distant sites using a proprietary, PC-based implementation of H.320 video conferencing over a TCP/IP network connected to the Internet2. The receiving sites participated in two-way, real-time video and audio communications and graded the quality of the signal they received. RESULTS: On August 25, 1998, a laparoscopic Nissen fundoplication was transmitted to Internet2 stations in Colorado, Pennsylvania, and to an Internet station in New York. On September 28 and 29, 1998, we broadcast laparoscopic operations throughout both days to the Internet2 Fall Conference in San Francisco, California. Most recently, on February 24, 1999, we transmitted a laparoscopic Heller myotomy to the Abilene Network Launch Event in Washington, DC. CONCLUSIONS: The Internet2 is currently able to provide the bandwidth needed for a turn-key video conferencing system with high-resolution, real-time transmission. The system could be used for a variety of teaching and educational programs for experienced surgeons, residents, and medical students.


Subject(s)
General Surgery/education , Internet , Laparoscopy/methods , Telemedicine , Humans , Internship and Residency , Video Recording
19.
J Gastrointest Surg ; 2(1): 72-8, 1998.
Article in English | MEDLINE | ID: mdl-9841971

ABSTRACT

The long-term sequelae of pancreaticoduodenectomy are not completely understood. In the present study nutritional status, pancreatic function, and subjective quality-of-life parameters were evaluated in 45 patients who had previously undergone either pylorus-preserving pancreaticoduodenectomy (PPPD) or standard pancreaticoduodenectomy (SPD). Quality-of-life parameters, as measured by the Short Form-36 health survey, demonstrated no significant differences between the subgroups and normal control subjects in six of the eight domains for physical and mental health. Patients who had undergone SPD were noted to have significantly lower scores for general health and vitality than either age-matched control subjects or those who had undergone PPPD. No differences in nutritional parameters or indicators of pancreatic exocrine function between the two groups were identified. An elevated hemoglobin A1c value was seen in only one patient who was not diabetic preoperatively. Our data indicate that long-term survivors of pancreaticoduodenectomy generally feel as good as their normal counterparts, although SPD may result in some health satisfaction deficits. Nutritional status and pancreatic exocrine function are not improved in patients undergoing a pylorus-preserving procedure, and postoperative pancreatic endocrine dysfunction is unusual in both groups.


Subject(s)
Pancreaticoduodenectomy , Attitude to Health , Case-Control Studies , Evaluation Studies as Topic , Female , Follow-Up Studies , Gastroenterostomy , Glycated Hemoglobin/analysis , Health Status , Humans , Jejunum/surgery , Male , Mental Health , Middle Aged , Nutritional Status , Pancreas/physiopathology , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/methods , Pancreaticoduodenectomy/psychology , Pancreaticojejunostomy , Patient Satisfaction , Pyloric Antrum/surgery , Pylorus/surgery , Quality of Life , Survivors , Treatment Outcome
20.
J Surg Res ; 79(2): 154-7, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9758731

ABSTRACT

BACKGROUND: Dehydroepiandrosterone (DHEA), an androgen precursor, inhibits the induction of pancreatic cancer in some animal models. Our laboratory has previously demonstrated that the sulfated form of DHEA (DHAS), when administered by intraperitoneal injection, inhibits the growth of pancreatic cancer xenografts in nude mice. In the present study, we hypothesize that DHEA-mediated pancreatic cancer growth inhibition is associated with alterations in plasma sex hormone concentrations. MATERIALS AND METHODS: Forty male, nude, athymic mice were fed either Teklad 22/5 rodent diet or diet supplemented with 0.6% DHEA ad libitum. Four weeks following the institution of the experimental diets, 1 x 10(6) MiaPaCa-2 cells were injected into the right flank of each animal. Tumor area was recorded weekly and tumor weights were measured after 5 weeks. Plasma DHAS, testosterone, and progesterone concentrations were determined by radioimmunoassay. RESULTS: Plasma DHAS, testosterone, and progesterone concentrations were all significantly elevated in the DHEA-treated group. DHEA-treated mouse plasma DHAS concentrations were approximately 50-fold higher than controls. Mean tumor weight was significantly reduced in the DHEA group (68.9 +/- 39.1 vs 121.0 +/- 64.3). DHEA treatment did not result in significant animal weight reductions and toxic side effects were not observed. CONCLUSIONS: Dietary supplementation with 0.6% DHEA causes significant elevations in plasma DHAS concentration. DHEA administration significantly inhibits pancreatic cancer cell growth at plasma concentrations 1 x 10(5)-fold lower than previously reported. The mechanism of action may involve elevated concentrations of sex hormones.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Dehydroepiandrosterone/administration & dosage , Pancreatic Neoplasms/pathology , Adjuvants, Immunologic/pharmacology , Administration, Oral , Animals , Body Weight/drug effects , Cell Division/drug effects , Dehydroepiandrosterone/pharmacology , Dehydroepiandrosterone Sulfate/blood , Humans , Male , Mice , Mice, Nude , Neoplasm Transplantation , Pancreatic Neoplasms/blood , Progesterone/blood , Reference Values , Testosterone/blood
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