Changing attitudes toward endolumenal therapy.

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.

Efficacy of percutaneous treatment of biliary tract calculi using the holmium:YAG laser.

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.

Endoscopic ablation of intestinal metaplasia containing high-grade dysplasia in esophagectomy patients using a balloon-based ablation system.

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.

Thin-layer ablation of human esophageal epithelium using a bipolar radiofrequency balloon device.

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.

Heating and humidifying of carbon dioxide during pneumoperitoneum is not indicated: a prospective randomized trial.

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.

Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors: an analysis of p16/MTS1 tumor suppressor gene inactivation.

Neoplasms of the endocrine pancreas are extremely rare, and molecular mechanisms influencing their development are poorly understood. Nevertheless, gastrinomas have become a paradigm for the study of hormonally active tumors. In the present study, 12 gastrinoma and nonfunctioning pancreatic neuroendocrine tumor specimens were evaluated for genetic alterations of the p16/MTS1 tumor suppressor gene. DNA extracted from microdissected portions of paraffin-embedded tumor sections were examined for mutations and homozygous deletions using "Cold" single-strand conformation polymorphism and semiquantitative PCR-based analyses, respectively. Samples were also analyzed for the presence of 5' CpG island hypermethylation using methylation-specific PCR. The p16/MTS1 gene was found to be homozygously deleted in 41.7% of tumors and methylated in 58.3%, but no mutations were identified by single-strand conformation polymorphism analyses. Overall, 91.7% of the specimens demonstrated inactivating alterations in p16/MTS1. These data suggest that transcriptional silencing of p16/MTS1 is a frequent event in these rare and poorly understood tumors.

Oxythiamine and dehydroepiandrosterone inhibit the nonoxidative synthesis of ribose and tumor cell proliferation.

This study investigates the significance of the glucose-6-phosphate dehydrogenase (G6PD) catalyzed oxidative and the transketolase (TK) catalyzed nonoxidative pentose cycle (PC) reactions in the tumor proliferation process by characterizing tumor growth patterns and synthesis of the RNA ribose moiety in the presence of respective inhibitors of G6PD and TK. Mass spectra analysis of 13C-labeled carbons revealed that these PC reactions contribute to over 85% of de novo ribose synthesis in RNA from [1,2-(13)C]glucose in cultured Mia pancreatic adenocarcinoma cells, with the fraction synthesized through the TK pathway predominating (85%). Five days of treatment with the TK inhibitor oxythiamine (OT) and the G6PD inhibitor dehydroepiandrosterone-sulfate (0.5 microM each) exerted a 39 and a 23% maximum inhibitory effect on cell proliferation in culture, which was increased to 60% when the two drugs were administered in combination. In vivo testing of 400 mg/kg OT or dehydroepiandrosterone-sulfate in C57BL/6 mice hosting Ehrlich's ascitic tumor cells revealed a 90.4 and a 46% decrease in the final tumor mass after 3 days of treatment. RNA ribose fractional synthesis through the TK reaction using metabolites directly from glycolysis declined by 9.1 and 23.9% after OT or the combined treatment, respectively. Nonoxidative PC reactions play a central regulating role in the carbon-recruiting process toward de novo nucleic acid ribose synthesis and cell proliferation in vitro and in vivo. Therefore, enzymes or substrates regulating the nonoxidative synthesis of ribose could also be the sites to preferentially target tumor cell proliferation by new anticancer drugs.

Identification and sequencing of the Syrian Golden hamster (Mesocricetus auratus) p16(INK4a) and p15(INK4b) cDNAs and their homozygous gene deletion in cheek pouch and pancreatic tumor cells.

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.

Laparoscopic splenectomy in the management of immune thrombocytopenia purpura.

The role of splenectomy in the management of immune thrombocytopenia purpura is well known. Recent improvements in laparoscopic technology have significantly expanded the variety of general surgical procedures amenable to a minimally invasive approach. An initial experience of four cases of immune thrombocytopenic purpura managed by laparoscopic splenectomy is presented. The entire procedure was completed under laparoscopic guidance in three of four cases, and a counterincision was required to control bleeding in one patient. The procedure is performed with five operating ports including a camera port, two retraction ports, and two dissection ports. Dissection begins at the lower pole of the spleen and progresses cephalad to the hilum where major vessels are individually ligated and divided. The short gastric vessels are divided with a linear laparoscopic stapler. The lateral peritoneal attachments are divided, and the spleen is removed intact through a 6 cm fascial incision at the umbilicus. Laparoscopic splenectomy appears to be a safe and efficacious procedure that is useful in the management of certain hematologic diseases and may ultimately be performed for a variety of pathologic conditions involving the spleen.

Long-term prognosis of Zollinger-Ellison syndrome in multiple endocrine neoplasia.

BACKGROUND: The long-term prognosis of Zollinger-Ellison Syndrome (ZES) is not well defined. The findings of other endocrinopathies, the need for long-term surveillance, and the role of surgical treatment are controversial. METHODS: To help provide more information about these topics the records of 76 patients with ZES were reviewed. RESULTS: Nineteen patients with gastrinoma had multiple endocrine neoplasia (MEN). Fifteen had hyperparathyroidism from 14 years before to 38 years after the diagnosis of ZES. Three patients had pituitary adenomas. The unusual findings of pheochromocytoma were also seen in three patients. Sixteen patients were followed at least 10 years and 12 were followed for more than 20 years. Surgical cure was achieved in only one patient after a 12-year follow-up. The actual 5-, 10-, 15-, and 20-year survival rates of 94%, 75%, 61%, and 58%, respectively, were compared with patients with sporadic ZES with 5-, 10-, 15-, and 20-year survival rates of 62%, 50%, 37%, and 31%, respectively. CONCLUSIONS: Multiple endocrinopathies are common but are rarely diagnosed synchronously, mandating life-long surveillance for patients with ZES. Long-term prognosis is good. Survival is longer for patients with ZES and MEN compared with patients with sporadic ZES. Surgical cure is rare. Surgical excision without a single localized lesion does not seem justified.

Dehydroepiandrosterone-sulfate inhibits pancreatic carcinoma cell proliferation in vitro and in vivo.

BACKGROUND: Dehydroepiandrosterone-sulfate (DHEA-S) is a potent inhibitor of glucose-6 phosphate dehydrogenase, the rate limiting enzyme of the hexose monophosphate shunt, a biochemical pathway that provides substrate for DNA synthesis in neoplastic tissue. DHEA-S has been shown to inhibit the growth of neoplasms arriving from human skin, lung, colon, and mammary tissue. This study evaluates the effect of DHEA-S on human pancreatic cancer cell lines in vitro and in vivo. METHODS: In vitro, the human pancreatic adenocarcinoma cell lines MiaPaCa-2, Capan-1, Capan-2, CAV and Panc-1 were treated with concentrations of 1.9 mumol/L to 1000 mumol/L DHEA-S in 1% dimethylsulfoxide (DMSO) for 5 consecutive days. Cell proliferation was determined by a nonradioactive cell proliferation assay and compared with DMSO treated controls. In vivo testing was performed by inoculating two cell lines, MiaPaCa-2 and Panc-I, into the flank of 40 male nude athymic mice in four study groups. After 1 week of growth, 667 mg/kg DHEA-S in 1% DMSO or 0.2 ml 1% DMSO alone in the control group was administered by daily intraperitoneal injection. Body weight and tumor size was recorded weekly, and tumor weight was measured after 3 weeks of treatment. RESULTS: In vitro cell proliferation was decreased in the five cell lines by 36% to 62% of controls (p < 0.001) at 500 mumol/L DHEA-S. In vivo, after 2 weeks, tumor size was only 76% (p < 0.008) and 67% (p < 0.005) of the controls. After 3 weeks of treatment, tumor size was 73% (p < 0.001) and 53% (p < 0.001) of controls, and tumor weight was decreased by 73% in MiaPaCa-2 (p < 0.001) and 66% in Panc-1 (p < 0.001). Radioimmunoassay measurements of DHEA-S and testosterone from DHEA-S treated mouse plasma showed a significant increase in circulating levels of these hormones. CONCLUSIONS: DHEA-S achieves high serum levels after intraperitoneal injection without elevation of serum testosterone levels and produces no significant toxicity. Treatment with DHEA-S results in a significant reduction of proliferation of human pancreatic cancer cells in culture and when grown as subcutaneous tumors in athymic nude mice.

Indium-111-pentetreotide scanning versus conventional imaging techniques for the localization of gastrinoma.

BACKGROUND: The present study evaluates 111In-pentetreotide scanning as a method for detection of gastrinomas. Operative findings serve as the benchmark for comparison of the efficacy of 111In-pentetreotide versus conventional imaging studies. METHODS: Twelve patients (seven female and five male; age, 37 to 80 years) with histologic confirmation of gastrinoma underwent thin section dynamic computed tomography (CT) scanning and 111In-pentetreotide scanning. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 111In-pentetreotide and CT scanning are compared on the basis of tumor size and location. RESULTS: Thirty discrete foci of intrahepatic and extrahepatic tumors were detected at operation. CT scanning detected three of nine pancreaticoduodenal lesions, whereas eight of these nine extrahepatic primary tumors were imaged by 111In-pentetreotide scanning. No false-positive 111In-pentetreotide scans were noted. The sensitivity of CT scanning for detection of metastatic disease was 56% versus 94% for the 111In-pentetreotide scan. Successful CT imaging was highly dependent on tumor size. No tumor smaller than 1 cm was imaged by CT, whereas four of seven lesions greater than 1 cm were imaged by 111In-pentetreotide scintigraphy. The smallest gastrinoma imaged by 111In-pentetreotide scanning was a 4 mm duodenal tumor. CONCLUSIONS: 111In-pentetreotide scanning was superior to CT scanning for localizing gastrinomas. Further studies are required to determine whether 111In-pentetreotide scans will complement or replace traditional imaging methods.

Reducing overtriage without compromising outcomes in trauma patients.

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.

Detection of aerosolized cells during carbon dioxide laparoscopy.

Laparoscopic surgery for malignancy has been complicated by port-site recurrences. The exact mechanism has yet to be defined. In vitro studies suggest that carbon dioxide-induced tumor cell aerosolization may play a role. We have attempted to document this in a human model. Patients scheduled for elective laparoscopy underwent port placement and abdominal insufflation with carbon dioxide. A suction trap was then filled with 40 cc of normal saline solution and attached to an insufflation site on the port. The carbon dioxide effluent was directed through the saline. The specimen was concentrated, resuspended, and transferred to a slide. A Papanicolaou stain was used. Thirty-five specimens were obtained. Fifteen patients (37%) had malignant disease, which was metastatic in eight. Five patients had carcinomatosis. In two of those with carcinomatosis, staining revealed a large number of malignant cells. Malignant cells were not found in any other patients. In two patients, however, aerosolized mesothelial cells were identified. Follow-up ranged from 2 to 7 months. One patient who displayed cellular aerosolization developed a port-site recurrence. We conclude that malignant cells are aerosolized but only during laparoscopy in the presence of carcinomatosis. It is unlikely that tumor cell aerosolization contributes significantly to port-site metastasis.

Outcome analysis of long-term survivors following pancreaticoduodenectomy.

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.

Thiamine supplementation to cancer patients: a double edged sword.

The objectives of this review are to (a) explain the mechanism by which thiamine (vitamin B1) promotes nucleic acid ribose synthesis and tumor cell proliferation via the nonoxidative transketolase (TK) pathway; (b) estimate the thiamine intake of cancer patients and (c) provide background information and to develop guidelines for alternative treatments with antithiamine transketolase inhibitors in the clinical setting. Clinical and experimental data demonstrate increased thiamine utilization of human tumors and its interference with experimental chemotherapy. Analysis of RNA ribose indicates that glucose carbons contribute to over 90% of ribose synthesis in cultured cervix und pancreatic carcinoma cells and that ribose is synthesized primarily through the thiamine dependent TK pathway (> 70%). Antithiamine compounds significantly inhibit nucleic acid synthesis and tumor cell proliferation in vitro and in vivo in several tumor models. The medical literature reveals little information regarding the role of the thiamine dependent TK reaction in tumor cell ribose production which is a central process in de novo nucleic acid synthesis and the salvage pathways for purines. Consequently, current thiamine administration protocols oversupply thiamine by 200% to 20,000% of the recommended dietary allowance, because it is considered harmless and needed by cancer patients. The thiamine dependent TK pathway is the central avenue which supplies ribose phosphate for nucleic acids in tumors and excessive thiamine supplementation maybe responsible for failed therapeutic attempts to terminate cancer cell proliferation. Limited administration of thiamine and concomitant treatment with transketolase inhibitors is a more rational approach to treat cancer.

Pancreatic pseudocysts following acute pancreatitis.

BACKGROUND: Pancreatic pseudocysts (PP) following acute pancreatitis have traditionally been approached by observation to allow cyst maturation. However, recent evidence suggests a selective approach toward management is indicated. METHODS: We retrospectively reviewed the presentation, operative management, and outcome of patients developing PP following acute pancreatitis since 1988. PP related to chronic pancreatitis were excluded. RESULTS: Twenty-seven patients were identified, 17 with giant PP (> 10 cm) and 10 with PP less than 10 cm. Groups were not different with respect to age and etiology of pancreatitis, predominantly biliary. Patients with giant PP had a significantly greater number of Ranson criteria at presentation and underwent drainage procedures earlier following their initial presentation. With respect to giant PP, 7 patients underwent internal drainage all via cystogastrostomy with 5 complications. Nine of 10 patients underwent urgent operation via external drainage. There were 3 pancreatic fistulas in this group. The morbidity and mortality rates for giant PP were 65% and 18% respectively. With respect to smaller PP, 8 underwent internal drainage with 1 death (mortality rate 10%). External drainage was performed in 2 patients with 1 pancreatic fistula (morbidity 10%). CONCLUSIONS: Patients with PP and a high Ranson score following acute pancreatitis are at significant risk for giant PP formation. Expectant management of giant PP is associated with higher morbidity and mortality than small PP suggesting that earlier external drainage, before clinical deterioration, may be beneficial. To be accurate, comparisons of outcomes for various treatment modalities must take into consideration PP size.

Laparoscopic skills enhancement.

BACKGROUND: Laparoscopy requires a unique subset of surgical skills that, for the inexperienced, can significantly delay the development of basic operative skills. We hypothesized that learning laparoscopic suturing and knot tying would improve laparoscopic skills. METHODS: A laparoscopic training seminar for junior surgical residents was established to test this hypothesis. Emphasis was placed on laparoscopic knot tying and suturing. Skills were assessed at the beginning and the end of the course. RESULTS: All residents showed significant improvement. Dominant and nondominant hand skills improved by 30.2% and 26.9%, respectively. Two-handed skills improved by 58.6% and 30.1%. Overall scores improved by 28.9%. CONCLUSIONS: A structured laparoscopic skills course stressing knot tying and suturing is an effective way to develop dexterity and significantly improve the performance of laparoscopic tasks. These improvements can be accomplished in a cost-effective curriculum that should enhance the surgical education of residents and speed the acquisition of competent operative skills.

Prophylactic cholecystectomy is not indicated following renal transplantation.

BACKGROUND: The appropriate management of gallstones in patients undergoing renal transplantation is controversial. Screening for gallstones and subsequent prophylactic cholecystectomy has been recommended by some authors for kidney transplant candidates. Our program does not practice routine pretransplant screening for gallstones, and we reviewed our data to determine the outcome of our management approach. METHODS: We reviewed the records of the 1,364 currently followed patients who have undergone kidney transplant at our institution since 1985 in order to evaluate the morbidity and mortality of biliary disease in the post-transplant period. We attempted to contact all patients by telephone or mail survey for the presence of biliary tract disease or operations. RESULTS: Six hundred and sixty-two patients were fully evaluated. Fifty-two (7.85%) required cholecystectomy for stone disease. Seven patients underwent incidental cholecystectomy during other operations, 2 patients developed acalculus cholecystitis, and 14 patients with asymptomatic cholelithiasis are being followed up. Surgical indications included 38 biliary colic, 9 acute cholcystitis, 3 gallstone pancreatitis, and 2 patients who were asymptomatic. Fifty-two patients underwent 30 laparoscopic cholecystectomies, 20 open cholecystectomies, and 2 conversions. Surgery occurred from 7 days to 9.6 years following transplantation. Overall, the median hospital stay (no postoperative stay) was 4 days (range 1 to 57). Patients undergoing laparoscopy had a median stay of 2 days compared with 7 days for those undergoing an open procedure. Complications were seen in 6 patients (11.5%) with no morbidity and no graft loss. The 1-, 2-, and 5-year graft survival was 98%, 96%, and 85%, respectively, in patients undergoing cholecystectomy. CONCLUSIONS: Transplant patients are not at an increased risk for developing biliary tract disease compared with nontransplant patients. Gallstone disease does not have a negative impact on graft survival. Treatment of gallstones has a low risk and does not represent an increased risk of complications in patients following renal transplantation.

Transmission of live laparoscopic surgery over the Internet2.

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.