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S K Libutti

Publications and source records attributed to S K Libutti.

89 records · Page 5Linked to original sources
PubMed1994

Characterization of a novel tumor-derived cytokine. Endothelial-monocyte activating polypeptide II.

Endothelial-monocyte activating polypeptide II (EMAP II) was initially identified in the supernatant of murine methylcholanthrene A-induced fibrosarcomas (Meth A) by its capacity to activate host effector cells (Kao, J., Ryan, J., Brett, J., Chen, J., Shen, H., Fan, Y-G., Godman, G., Familletti, P., Wang, F., Pan, Y-C., Stern, D., and Clauss, M. (1992) J. Biol. Chem. 267, 20239-20247). Based on the NH2-terminal protein sequence, a full-length cDNA has been cloned which indicates that the precursor of EMAP II is a unique, leaderless, single polypeptide chain with predicted molecular mass approximately 34 kDa and that the mature form released by Meth A cells corresponds to approximately 20 kDa. Purified recombinant mature EMAP II (EMAP II, approximately 20 kDa form) activated endothelial cells with resulting elevation of cytosolic free calcium concentration, release of von Willebrand factor, induction of tissue factor, and expression of the adhesion molecules E-selectin and P-selectin. Neutrophils exposed to EMAP II demonstrated elevated cytosolic free calcium concentration, peroxidase generation, and chemotaxis. EMAP II also activated mononuclear phagocytes elevating cytosolic free calcium concentration, inducing tumor necrosis factor-alpha (TNF) and tissue factor, and stimulating chemotaxis. Systemic infusion of EMAP II into C3H/HeJ or Balb/c mice was associated with systemic toxicity, pulmonary congestion, and the appearance of TNF, interleukin-1 and -6 in the plasma. A single intra-tumor injection of EMAP II into Meth A sarcomas induced acute thrombohemorrhage and partial tumor regression. Local injection of EMAP II into a tumor resistant to the effects of TNF, murine mammary carcinoma, rendered it sensitive to subsequently administered TNF, which resulted in acute thrombohemorrhage and partial regression. These data suggest that recombinant EMAP II, a tumor-derived cytokine, has properties of a proinflammatory mediator with the capacity to prime the tumor vasculature for a locally destructive process.

Amino Acid Sequence↗
PubMed1994

Laparoscopic resection of a nonparasitic liver cyst.

The spectrum of treatment options for symptomatic, benign, nonparasitic hepatic cysts has ranged from percutaneous aspiration to liver transplantation. Most large series have demonstrated that complete resection of the cyst is associated with the lowest rate of recurrence. However, a conventional open laparotomy may subject these patients to unacceptable morbidity given the benign nature of most of these lesions. We successfully performed a complete resection of a large hepatic cyst using a laparoscopic approach. Using an endoscopic GIA stapling device we were able to remove the cyst with minimal blood loss and in minimal operative time. The patient tolerated the procedure well, was discharged home on postoperative day 2, and in follow-up has been without recurrent symptoms.

Aged↗
PubMed1994

Preliminary results of laser tissue welding in extravesical reimplantation of the ureters.

One exciting potential use of laparoscopic technology is the extravesical reimplantation of the ureters. We have assessed the efficacy of laser-activated fibrinogen solder to close vesical muscle flaps over submucosal ureters (Lich-Gregoir technique) in a canine model. Four dogs were subjected to unilateral flap closures via a protein solder (indocyanine green and fibrinogen) applied to the bladder serosa and exposed to 808 nm. continuous wave diode laser energy. Contralateral reimplantation was performed using 4-zero vicryl muscle flap closures (controls). At 7, 14 and 28 days postoperatively, intravenous pyelograms confirmed bilateral ureteral patency. At intravesical pressures above 100 cm. H2O, there was no evidence of wound disruption in either group. Nondisrupted wound closures were sectioned and strained until ultimate breakage to determine tensile strength. At each study interval the laser-welded closures withstood greater stress than the controls. Although these data represent single tissue samples and are not amenable to statistical analysis, laser-welded closures appeared to be stronger at each study interval. In conclusion, laser-welded vesical wound closures appear at least as strong as suture closures in the canine model.

Animals↗
PubMed1994

Canine choledochotomy closure with diode laser-activated fibrinogen solder.

BACKGROUND: An alternative to mechanical stapling or hand suturing is needed to permit laparoscopic common bile duct exploration. We evaluated the strength and healing characteristics of canine choledochotomies sealed with a fibrinogen solder and a diode laser. METHODS: After creation of a 0.5 cm longitudinal choledochotomy, the edges were coapted with forceps, and a fibrinogen solder mixed with indocyanine green dye was applied. The solder was sealed in place with an 810 nm diode laser (125 W/cm2). RESULTS: Immediate mean leakage pressure was 264 +/- 7 mm Hg compared with 83 +/- 66 mm Hg in suture controls. This increased to 364 +/- 115 mm Hg at 2 days and was more than 510 mm Hg at 7 days. On histologic examination rapid reabsorption of the solder with no signs of inflammation or stenosis was seen. No episodes of dehiscence or peritonitis occurred. CONCLUSIONS: Laser soldering provides a watertight choledochotomy closure with adequate immediate strength allowing a reliable, technically feasible common bile duct exploration via a laparoscopic approach.

Animals↗
PubMed1992

The effects of laser-assisted fibrinogen bonding on suture material.

To evaluate the effect of laser-assisted fibrinogen bonding on the tensile strength of suture material, 10 types of sutures were exposed to various time intervals of diode laser energy after pretreatment with dye-enhanced fibrinogen solder. After exposure, each suture material was stressed on a tensometer and compared with nonlased suture material. Our results indicate that polytetrafluoroethylene suture material was virtually unaffected at all time intervals of exposure to laser energy. Polyester suture material retained 64.3% of its tensile strength at 60 sec of exposure to laser energy. White silk suture material maintained 80% of its initial tensile strength at 60 sec of exposure. These suture materials may be used safely in conjunction with laser-assisted fibrinogen bonding even if prolonged laser exposure is necessary. The other suture materials tested may be compromised significantly by prolonged exposure to laser energy and must be used with relatively shorter irradiation periods.

Biocompatible Materials↗
PubMed1992

Laser bonding of secondary bronchi with solvent--detergent-treated cryoprecipitate.

Management of bronchopleural fistula is a challenging clinical problem. Laser-assisted cryoprecipitate bonding techniques offer a means to fix precisely tissue glues into the fistulae through a bronchoscopic approach. Analogous studies exist using fibrin glue with thrombin. Using a canine model, secondary bronchi were sealed with cryoprecipitate made from solvent/detergent-treated plasma (treated to inactivate membrane-enveloped virus) mixed with indocyanine green (absorption 805 nm). Diode laser energy (emission 808 nm, 7.3 W/cm 2) was applied to the solder until dessication was observed. Leakage pressures (n = 7) ranged between 18 and 86 mmHg with a mean of 46 +/- 24 mmHg. Laser-assisted solder techniques provide a reliably strong seal over leaking bronchial stumps and use of dye enhancement prevents undesired collateral thermal injury to surrounding bronchial tissue. Solvent/detergent plasma, prepared by methods shown to inactivate large quantities of HIV, HBV, and HCV, is an effective source of cryoprecipitate and should allow widespread use of pooled human material in a clinical setting.

Animals↗
PubMed1992

Alternative wavelengths for sutureless laser microvascular anastomosis: a preliminary study on acute samples.

Attempts to improve the speed and patency of microvascular anastomosis with laser-assisted techniques have provided a modest reduction in operative time and comparable success rates. Using sutureless microvascular anastomoses, 30 end-to-end anastomoses were created in the rat carotid artery using the gallium-aluminum-arsenide diode laser (808 nm). Indocyanine green and fibrinogen were applied to enhance tissue absorption of the laser energy and strengthen the bond created. These were compared with previously reported welds using the THC:YAG laser (2150 nm). Mean welding times were 140 and 288 s, and mean bursting pressures immediately after welding were 515 and 400 mmHg for the diode and THC:YAG laser groups, respectively. Histologically, both lateral and vertical spread of thermal damage was limited. Since both lasers create welds of adequate initial strength without stay sutures and are faster and easier to use than existing systems, evaluation of long-term patency would be worthwhile.

Anastomosis, Surgical↗
PubMed1992

Comparison of laser-assisted fibrinogen-bonded and sutured canine arteriovenous anastomoses.

The effect of laser-assisted fibrinogen bonding (LAFB) on the development of intimal hyperplasia was studied with stress-strain profiles and histologic evaluation of canine arteriovenous fistulas (AVFs). In 19 animals femoral AVFs were created with an 808 nm diode laser after topical application of fibrinogen mixed with indocyanine green dye; in the contralateral limb a sutured AVF was created. The animals were divided into three groups. Group 1 dogs (n = 6) were killed serially up to 4 weeks after surgery to examine the healing of the anastomoses created with LAFB. Group 2 dogs (n = 6) were killed 1 month after surgery, and the fresh specimens were strained axially to produce a stress-strain profile graph. Group 3 dogs (n = 7) were killed 7 months after surgery, and the AVFs were infused with formalin under pressure and histologically prepared to allow comparison of the ratio of maximum to minimum intimal hypertrophy. Fibrinogen used for LAFB was resorbed during the first month after operation without evidence of foreign body reaction or inflammation. Tensile break force was not significantly different in the laser-bonded group (4.6 +/- 2.4 pounds) and the sutured group (4.3 +/- 1.7 pounds). The modulus (tensile break force per square inch), a measure of elasticity, identified the laser-bonded AVF (149 +/- 44 pounds per square inch) to be less rigid than the sutured AVF (203 +/- 35 pounds per square inch) (p less than 0.05). No significant differences in the degree of intimal hyperplasia were noted in any area of the anastomoses. Use of LAFB neither accelerates nor prevents intimal hyperplasia in a canine AVF model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Skin closure with dye-enhanced laser welding and fibrinogen.

The topical application of wavelength-specific dye and fibrinogen has been used to enhance laser closure of vascular anastomoses. We compared the closure of skin incisions by two different dye-enhanced, fibrinogen-based laser welding systems [argon laser (power density 4.78 W/cm2) with fluorescein isothiocyanate dye (n = 32) and diode laser (power density 9.55 W/cm2) with indocyanine green dye (n = 32)] with closure by interrupted 5-0 nylon suture (n = 64) and examined tensile strength, hydroxyproline production, histology, and cosmesis. Two 3-cm full-thickness incisions were made on the shaved backs of 64 rats. One incision was closed with suture, whereas the other, after treatment with the appropriate dye, was welded with either argon- or diode-lasered fibrinogen. At postoperative days 5, 10, 15, and 28, the closure sites were harvested and sectioned for analysis. Initially, wounds closed with argon-lasered fibrinogen showed less inflammatory response, greater collagen production (34.61 +/- 0.74 mg/gm), and greater mean peak stress at rupture (64.85 lbs/in2) than those closed with suture (16.42 +/- 3.20 mg/gm, 26.68 lbs/in2) (p less than 0.05). By 15 days, both argon and diode laser closures are superior in strength and collagen production to suture closure (p less than 0.05). At 28 days, diode laser closures (1315.60 lbs/in2) are stronger than suture closures (998.09 lbs/in2), whereas both are stronger than argon laser closures (813.16 lbs/in2) (p less than 0.05). Cosmetically, argon-welded wounds consistently appeared finer and lacked cross-hatched suture scars.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

A preliminary study of dye-enhanced laser photosclerosis.

Laser ablation of veins after injection of wavelength-specific dyes to enhance and localize energy absorption could provide a useful adjunct to current treatment options. To enhance the absorption of diode laser energy at 808 nm, ear veins of 41 rabbits were infused with 2 to 3 ml of indocyanine green dye (maximum absorption, 805 nm) and exposed for 2 to 20 seconds. Animals were killed between 0 and 28 days after operation. Discrete time intervals of laser exposure exist during which various-sized vessels can be ablated without significant thermal injury to the overlying tissue. Small vessels (0.2 mm in diameter) blanch after 2 to 3 seconds of exposure, whereas medium-sized vessels (2 mm in diameter) require 8 to 10 seconds. Vessels can be ablated with a power density as low as 11.1 W/cm2. Specimens taken immediately after laser exposure show vessel wall thinning and a reirradiation effect, created as laser energy initially absorbed by dye is reemitted. By the seventh day after operation, a brisk inflammatory response and acanthosis of the overlying epidermal layer develop. The lumen is partially filled by thrombus with cellular invasion. By postoperative day 28, the epidermal thickening and inflammatory reaction have resolved; the vessel walls are fibrotic. The use of low-power, air-cooled diode lasers, in conjunction with wavelength-specific dyes, may provide a simple, viable, and cosmetically appealing alternative to the treatment of superficial varicosities of the extremities.

Animals↗
PubMed1990

Canine colonic anastomoses reinforced with dye-enhanced fibrinogen and a diode laser.

Leakage from colonic anastomoses is a common cause of morbidity in patients recovering from bowel surgery. We evaluated a technique of laser-fibrinogen reinforcement to strengthen colonic anastomoses in a canine model. After creation of eight single-layer interrupted suture anastomoses in six dogs, indocyanine green-dye-enhanced fibrinogen was topically applied to the serosal surface and exposed to 808 nm diode laser energy. Immediately following colonic anastomosis, the mean leakage pressure was 137 +/- 22 mm Hg in the group (n = 8) using sutures alone and 326 +/- 67 mm Hg (P less than 0.001) in the group (n = 8) after the sutured anastomosis was reinforced with lasered-fibrinogen. On histological examination, no evidence of thermal injury to the tissue edges was noted and a layer of fibrinogen bridged the anastomotic gap. Laser dye-enhanced fibrinogen reinforcement significantly enhances the strength of sutured colonic anastomoses without causing appreciable thermal injury to the host tissues.

Anastomosis, Surgical↗
PubMedDate not supplied

Isolated organ perfusion does not result in systemic microembolization of tumor cells.

BACKGROUND: Isolated organ perfusion with hyperthermia and melphalan with or without tumor necrosis factor-alpha has been effectively used to treat regionally confined, unresectable malignancies of both the limb and liver. Many patients, however, will eventually relapse at distant sites. We used reverse transcription-polymerase chain reaction (RT-PCR) to determine whether significant tumor microembolization occurs in patients undergoing isolated limb perfusion (ILP), isolated hepatic perfusion (IHP), or hepatic resection. METHODS: Primers specific for the human tyrosinase gene or carcinoembryonic antigen gene were designed for RT-PCR to screen melanoma or colon adenocarcinoma, respectively. RNA from human melanoma lines (Pmel and 1286) and human colon adenocarcinoma lines (H508 and HT29) were used to generate positive control cDNA. Normal human blood was inoculated with tumor cells at concentrations that ranged from 10(-2) to 10(5) tumor cells/ml of blood to define the sensitivity. Systemic and perfusate blood samples were drawn from 15 patients (8 patients underwent IHP, 5 patients underwent ILP, and 2 patients underwent resection) before the start of the operation, immediately before and during the perfusion, and postoperatively. Mononuclear cell fractions were separated from the blood samples and RNA was extracted for the RT-PCR assay. Standard primers for human beta-actin were used to confirm that cDNA was generated after the RT reaction. RESULTS: RT-PCR assay sensitivity was determined to be 10 tumor cells/ml of whole blood. Of the 8 IHP patients, 6 had colon metastases and 2 had ocular melanoma metastases to the liver. All 5 ILP patients had in transit melanoma of the extremity. Two patients with colon metastases to the liver were found to have resectable disease. There were no detectable circulating tumor cells in the systemic circulation either preoperatively or postoperatively in all 15 patients that were screened. CONCLUSIONS: RT-PCR is a highly sensitive method of detecting tumor cells in perfusate or blood. Manipulation of the limb or liver followed by resection or isolated hyperthermic perfusion does not cause detectable release of circulating tumor cells. The late development of distant metastases observed in many of these patients does not correlate with the ability to measure circulating tumor cells during regional therapy.

Adenocarcinoma↗
PubMedDate not supplied

Endothelial monocyte-activating polypeptide II, a tumor-derived cytokine that plays an important role in inflammation, apoptosis, and angiogenesis.

The interactions between a tumor and its surrounding environment are complex and characterized by a variety of factors. Tumors produce a number of proteins that enable them to recruit a vascular supply, invade into surrounding tissues, and metastasize to distant sites. The host, in turn, responds to these signals by producing its own repertoire of molecules that may either assist or prevent the actions of the tumor. A thorough understanding of this relationship is critical to the development of novel anti-cancer therapies. The tumor-derived cytokine endothelial monocyte-activating polypeptide II (EMAP-II) has profound effects on the tumor as well as on host response. These effects target the inflammatory cascade as well as the processes involved in angiogenesis. In this review the authors describe the current understanding of the role of EMAP-II in inflammation, apoptosis, and angiogenesis and use this molecule to illustrate the complex interactions that occur in the tumor microenvironment.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Gadolinium-enhanced 3D MRA prior to isolated hepatic perfusion for metastases.

PURPOSE: Isolated hepatic perfusion (IHP) is a new treatment for patients with isolated unresectable liver metastases, which can result in a partial or complete response in approximately 75% of patients. Preoperative knowledge of hepatic arterial anatomy is important to adequately perfuse the liver. Digital subtraction angiography (DSA) is currently used to identify the hepatic arterial anatomy. The purpose of this study was to determine if MR angiography (MRA) could replace DSA prior to IHP. METHOD: Twenty-seven patients scheduled to undergo IHP underwent MRA with a contrast-enhanced 3D time-of-flight gradient echo sequence. Both maximal intensity projections (MIPs) and source coronal images were used to evaluate the images. The results of the MRA were interpreted by two readers who were blinded to the surgical results. The first 17 patients also underwent DSA, and a separate comparison was made with those results. Anatomy was characterized as either normal hepatic arteries (NHAs), normal vasculature with an accessory left hepatic artery (aLHA), or a replaced right hepatic artery (rRHA). RESULTS: MRA correctly detected all 22 patients with NHAs but also identified 6 aLHAs, of which only 2 were confirmed surgically. MRA correctly detected all five rRHAs. MIP images alone accurately depicted the hepatic arterial anatomy in only 9 of 27 (33%), usually because significant vessels were not visualized or their origin could not be determined. Source coronal images were required to accurately determine the anatomy in all patients. Among the 17 patients who underwent DSA, MRA detected 14 of 14 with NHA and 3 of 3 with rRHA. Six aLHAs were identified by MRA and five were confirmed by DSA. CONCLUSION: Enhanced 3D MRA is an accurate method of depicting the hepatic arterial supply. In comparison to surgery, MRA overestimates the number of aLHAs, but this may be because these small vessels are not detected at surgery. Based on the results of this study, DSA has been replaced by MRA in the planning of IHP at our institution. A better display of MRA images is needed as MIP images were usually insensitive for the small caliber arteries supplying the liver.

Angiography, Digital Subtraction↗
PubMedDate not supplied

Continuous hyperthermic peritoneal perfusion with cisplatin for the treatment of peritoneal mesothelioma.

PURPOSE: Peritoneal mesothelioma remains a difficult therapeutic challenge. Aggressive debulking combined with continuous hyperthermic peritoneal perfusion (CHPP) using cisplatin (CDDP) is a novel strategy for the treatment of peritoneal mesothelioma, allowing high regional delivery of chemotherapeutics and hyperthermia while minimizing systemic toxicity. PATIENTS AND METHODS: From June 1993 to May 1996, 10 patients with peritoneal mesothelioma (six men, four women; mean age 40 years, range 15-57) underwent tumor debulking followed by a 90-minute CHPP. CHPP parameters included mean initial CDDP of 120 micrograms/mL (range 81-166), perfusate volume 5.2 L (range 4-7), flow 1.5 L/min, intraperitoneal temperature at three locations-41.5 degrees C, 40.5 degrees C, 41.1 degrees C, and core temperature 38.4 degrees C (range 37.2 degrees C-39.5 degrees C). Nine of 10 patients had malignant peritoneal mesothelioma, eight with associated ascites, while the tenth had a symptomatic, multiply recurrent benign peritoneal mesothelioma. Nine of 10 patients were optimally debulked. Pharmacokinetics were performed on blood and perfusate samples on nine patients; CDDP levels were quantitated by atomic absorption spectroscopy. RESULTS: Total perfusate cisplatin AUC was a mean of 21-fold higher (range 2- to 116-fold) than total serum cisplatin AUC, and serum CDDP behaved similarly to systemically administered CDDP. Median follow-up after CHPP is 10 months (range 2-32), with no treatment-related mortality. In eight optimally debulked patients there is no evidence of recurrent disease clinically or by CT or MRI. Seven patients with symptomatic ascites have been completely palliated. CONCLUSIONS: CHPP with CDDP is well tolerated with no significant regional toxicity. Because favorable CDDP pharmacokinetics suggest the potential for enhanced CDDP tumoricidal effect during CHPP, tumor debulking and CHPP may represent an effective strategy for the treatment of peritoneal mesothelioma.

Adolescent↗