Five years' experience of PAS Port intravenous access system in adult cystic fibrosis.

An implantable venous access system provides a reliable and painless entry site for intravenous treatment. This study reports the authors' experience with such a system in adult patients with cystic fibrosis. Sixty five (87%) of 75 PAS Ports were placed successfully in 57 patients with cystic fibrosis. Because of early difficulties in advancing the catheter in patients whose veins had been traumatized by repeated courses of intravenous antibiotics, a technique was developed whereby venous entry was gained by direct subclavian puncture. This catheter insertion method was used in 53 (82%) attempts and the catheter was then passed by subcutaneous tunnelling to the port site on the ventral aspect of the upper arm. Fifty seven (88%) insertions were successful under local anaesthetic. The major early and late complications were iatrogenic pneumothorax (six cases) and infection (five cases), respectively. Late complications were more common when there was coexisting disease, e.g. diabetes mellitus, or an acute severe respiratory exacerbation, or when the Port was used for parenteral feeding. In conclusion, the PAS Port can be inserted safely by direct subclavian puncture. It was well tolerated and universally liked by the patients.

Laparoscopic colorectal surgery.

Laparoscopic surgery has been readily adapted to the management of patients with colorectal disease without any large-scale randomized clinical studies to support its use, particularly in patients with colorectal cancer. This overview analyses the currently available data and highlights the areas where caution is merited and optimism encouraged.

1997 Harry M. Vars Research Award. Does the route of feeding modify gut barrier function and clinical outcome in patients after major upper gastrointestinal surgery?

BACKGROUND: Direct experimental evidence suggests that total enteral nutrition (TEN) reduces septic morbidity compared with bowel rest and total parenteral nutrition (TPN) and that mucosal support and maintenance of gut barrier function is a key mechanism. This effect is supported indirectly by clinical studies, but this question has not previously been investigated directly in the postoperative patient. This study examined the hypothesis that early enteral feeding after major upper gastrointestinal surgery may modulate gut barrier function and decrease the risk of major infective complications compared with bowel rest and parenteral nutrition. METHODS: A randomized clinical trial of 67 patients (TPN = 34; TEN = 33) fed postoperatively for 7 days was performed. Thirty-day major morbidity and mortality were monitored. Intestinal permeability was measured using the lactulose/mannitol test preoperatively and on postoperative days 1 and 7. Systemic anti-endotoxin core immunoglobulin G and M antibodies and serum albumin and C-reactive protein were quantified at these time points. RESULTS: No clinical benefit was observed in patients fed enterally compared with the parenterally fed group. Intestinal permeability was increased on the 1st postoperative day in association with evidence of endotoxin exposure. By day 7, enteral feeding compared with parenteral feeding had failed to significantly influence any of the gut barrier or systemic parameters. CONCLUSIONS: This randomized controlled trial of TEN vs TPN after major upper gastrointestinal surgery failed to show a clinical benefit for the enteral route. Moreover, enteral nutrition did not modulate gut barrier function postoperatively.

Effects of albumin coating of knitted Dacron grafts on transinterstitial blood loss and tissue ingrowth and incorporation.

Transinterstitial blood loss at implantation and the degree of graft incorporation and inner capsule thickening was compared in serial explants of albumin-coated Dacron versus blood preclotted Dacron grafts in the canine thoracoabdominal aortic position (8 mm internal diameter x 30 cm length). The coated grafts were Bard DeBakey Vasculour II knitted Dacron prostheses impregnated with carbodiimide-cross-linked human albumin. Control grafts were otherwise identical and preclotted with the recipients' whole blood before heparinization during surgery. Transinterstitial blood loss after establishing flow was measured by weighing sponges wrapped around the grafts. Albumin pretreatment resulted in significantly less median blood loss (5.1 g versus 11 g, P=0.04; Mann-Whitney rank sum test). Grafts were explanted at 1 week, 4 weeks, 10 weeks, and 20 weeks. Patency was 100% in both groups. Graft incorporation at explantation was graded by the surgeon as: 1 = none, 2 = minimal, 3 = moderate, or 4 = extensive. No significant differences were noted at any time period. Inner capsule thickness measurements were made every 2.5 mm along the length of all explants. Grafts explanted at 1 week displayed no inner capsules. By 20 weeks, median inner capsule thickness was significantly less in albumin-coated grafts (190 microm versus 235 microm; P<0.0001). These inner capsules in both groups formed as islands, containing abundant myofibroblasts and collagen, covered by endothelial cells and surrounded by residual fibrin coagula. In conclusion, albumin-coated knitted Dacron grafts displayed less transinterstitial blood loss at implantation, and qualitatively similar incorporation, but significantly thinner inner capsules at 20 weeks.

Administration of peripheral parenteral nutrition: a prospective study comparing rotation of venous access sites with ultrafine cannulas.

Peripheral veins have been used successfully for patients requiring short- to medium-term total parenteral nutrition. This study prospectively compares two methods of peripheral parenteral nutrition (PPN). Forty-six patients requiring parenteral nutrition (PN) were identified prospectively. Fifty courses of PPN were prescribed using a standardized PPN formula of 9.3 g nitrogen, 1400 kCal, 2500 ml (KABI II, Pharmacia). Patients were randomized to receive PPN via 23G, 15 cm flexane catheters (Nutriline) inserted into an antecubital vein which remained in-situ with a continuous infusion over 24 h, or to receive 12-h cyclical infusions through peripherally sited 18G catheters (Venflon) which were removed postinfusion and reinserted into the contralateral forearm on alternate days. Data collected included duration, complications and cost of materials for each prescribed course. A scoring system to determine patient anxiety and depression and a questionnaire regarding patients' perspectives were evaluated. Fifty courses were prescribed, 26 by rotation of veins (RV) and 24 by Nutriline (N). Mean duration of feeding was 7.9 and 8.6 days, respectively; cost of materials were comparable 6.48/day (RV) vs 5.17/day (N); 2 RV patients failed to complete their course (no access [P< 0.05], whilst 9 N patients failed to complete their course (4 severe phlebitis, 2 no venous access, 2 septicaemia, 1 dislodged). Five patients required CPN (RV, N 3) while 4 remaining patients were fed by an alternative PPN method. The overall incidence of anxiety was 20% and of depression 16%, with no significant difference between groups. The majority of patients (87%) found mobility restricted. Twelve-hourly infusions via alternate forearm veins were significantly more successful than continuous infusions via Nutriline, both in terms of completion of the prescribed course and less venous morbidity. This study confirms that rotation of forearm veins allows affordable and successful PN administration to the majority of patients, with low PN-related morbidity.

Impaired gut barrier function in malnourished patients.

The gastrointestinal tract is essential to host defence, acting as a barrier to absorption and translocation of gut antigens, including bacteria. In experimental models, protein malnutrition is permissive to gut barrier failure and endogenous infection. A clinical correlate has not been described. Intestinal morphology and barrier function to food protein antigens was studied in malnourished patients. Thirty-five individuals were evaluated, 20 malnourished patients and 15 well nourished hospital controls. Morphology was assessed from endoscopic biopsies of the second part of the duodenum, and serum immunoglobulin (Ig) G antibodies to gliadin and beta-lactoglobulin were measured. No antibody to food proteins was evident in the control group. In contrast, serum IgG antibodies to at least one antigen were present in 15 malnourished patients and to both antigens in ten (P < 0.0001 versus controls). Severely malnourished patients were more likely to have both antibodies present than those with mild or moderate malnutrition (P < 0.05). Antibody-positive malnourished patients had significantly better nutritional status than antibody-negative patients with malnutrition (P < 0.05). In no group of patients was there morphological evidence of abnormal mucosa or an immunological infiltrate. Gut barrier function is compromised in malnourished patients which suggests a mechanism that may facilitate gut-derived infection and sepsis.

Prospective study of the aetiology of infusion phlebitis and line failure during peripheral parenteral nutrition.

Four techniques of administering peripheral parenteral nutrition (PPN) were examined prospectively to investigate the role of mechanical trauma in the development of infusion phlebitis. Patients in group 1 (n = 15) were fed via a standard 18-G Teflon cannula which was removed on completion of the infusion and was rotated to the contralateral arm every day. Group 2 patients (n = 15) had a similar catheter sited in each forearm simultaneously, with rotation of the side of infusion each day. Patients in group 3 (n = 17) had a 15-cm Silastic rubber catheter inserted into a forearm vein and a standard cannula sited in the contralateral forearm, with alternation of infusion each day. Those in group 4 (n = 13) had a fine-bore 23-G silicone catheter sited in one arm only. Patients in groups 1, 2 and 3 were fed over 12-h cycles and those in group 4 for a 24-h continuous cycle. A total of 408 patient-days of PPN were given. Mean duration of PPN in groups 1-4 was 7.5, 9, 5.5 and 5 days respectively. Infusion phlebitis was not recorded in patients who had a daily change of cannula (group 1), but occurred in four patients in group 2, eight in group 3 and eight in group 4. Phlebitis scores were 0, 9, 15 and 12 for groups 1-4 respectively. Severe phlebitis and line occlusion occurred more frequently in patients with a 15-cm catheter (group 3) and in those fed continuously over 24 h (group 4). These results suggest that mechanical trauma is an important factor in the aetiology of infusion phlebitis. This can be minimized by reducing the time for which the vein wall is exposed to nutrient infusion and by reducing the amount of prosthetic material within the vein.

Staged resection or primary anastomosis for obstructing lesions to the left colon.

The management of obstructing left-sided colonic and rectal lesions has traditionally been by a staged procedure. The introduction of 'on-table lavage', has made primary resection and anastomosis of the large bowel feasible for patients presenting as emergencies. We have studied the perioperative course of 28 patients who presented with left colonic obstruction to determine whether primary anastomosis conferred additional morbidity. The patients ranged in age from 29 to 89 years (mean 66 years) at presentation. The ASA status of patients was comparable in both groups (Table 1). Fourteen patients underwent resection, on-table lavage, and primary anastomosis (PA) and 14 a Hartmann's procedure (HP). The mean operative time for the PA procedure was 200 minutes compared to 110 minutes for the HP group. There was no significant difference in the postoperative complication rate nor mean hospital stay rate for the primary procedures between the two groups. There was no clinical anastomotic leak in patients undergoing primary anastomosis. However secondary surgery for patients undergoing colorectal reconnection conferred added morbidity for patients who had a HP. We conclude that resection, on-table lavage, and primary anastomosis is safe in the management of left-sided colonic obstruction and in most cases is the treatment of choice.

Dacron stimulation of macrophage transforming growth factor-beta release.

This study evaluated the effect of Dacron on the release of macrophage transforming growth factor-beta (TGF-beta),an endothelial cell growth inhibitor. Rabbit peritoneal macrophages were grown in minimum essential medium (MEM) with 10% fetal bovine serum (FBS) in the presence or absence of Dacron (0.5 mm x 3 mm particles). Media were collected three times each week for 7 weeks. For the TGF-beta bioassay, mink lung epithelial cells (CCL64) were grown in MEM with 10% FBS. Test-conditioned media, 100 mu 1, were added (n = 4), and incubated 48 h. 3(H)-Thymidine (3(H)-TdR) uptake was determined and compared with 3(H)-TdR uptake using known pure TGF-beta standards. Media samples were additionally pre-incubated with a neutralizing anti-TGF-beta(1) antibody and the 3(H)-TdR uptake again quantitated. TGF-beta activity in the conditioned media of macrophages exposed to Dacron exceeded the control media groups in all weeks, reaching significance (P<0.05) in weeks 3, 4,5, 6 and 7. Pre-incubation of media samples with the anti-TGF-beta antibody inhibited this TGF-beta activity in all weeks with statistical significance in weeks 1, 2, 3, 5 and 7. The inhibitory effects of Dacron on endothelialization may be explained by the Dacron-induced release of TGF-beta from macrophages.

Gut barrier failure in experimental obstructive jaundice.

Bacterial translocation from the gastrointestinal tract is central to current concepts of endogenous sepsis. Studies were designed to evaluate the potential relevance of translocation to the high incidence of infection in obstructive jaundice. Sprague-Dawley rats underwent laparotomy and division of the bile duct or sham ligation. In Study 1, rats were sacrificed after 24 hr, 1 week, and 3 weeks and the mesenteric lymph node complex, cecum, and blood were cultured and plasma endotoxin was measured. In Studies 2 and 3, sham-and bile duct-ligated rats were challenged after 1 week with operative trauma and intravenous endotoxin, respectively. Animals were sacrificed after a further 24 hr. No translocation was observed in sham-operated rats. Although colonization of the mesenteric lymph nodes was not seen in bile duct-ligated rats after 24 hr, this was evident in 75% of rats after 1 and 3 weeks. Surgical trauma and endotoxin produced bacterial translocation in 33 and 40%, respectively, of sham-operated animals; this was enhanced in bile duct-ligated rats to 75% (P < 0.01 vs shams) and 93% (P < 0.001 vs shams), respectively. Endotoxin resulted in positive blood cultures in 71% of jaundiced rats compared with none of the sham group injected with endotoxin (P < 0.001). Biliary obstruction produces bacterial translocation and this process is enhanced by surgical trauma and endotoxin. The data support the thesis of gut barrier failure in jaundice and suggest that therapies targeted toward decreasing bacterial translocation may merit evaluation in the prophylaxis and treatment of infection in the jaundiced patient.

High-dose interleukin 2 promotes bacterial translocation from the gut.

Toxicity associated with high-dose recombinant interleukin 2 (rIL-2) therapy simulates a sepsis syndrome, but the mechanism remains unclear. We hypothesised that translocated gut-origin bacteria may be important. Fifty-one male rats were randomised to receive rIL-2 by intraperitoneal injection at doses (IU) of 10(5) (n = 15), 10(4) (n = 8), 10(3) (n = 8) or 10(2) (n = 8) twice daily, or a saline bolus (n = 12). After 5 days, ileal histomorphology was assessed and the mesenteric lymph node complex cultured. Results showed that colonisation of mesenteric lymph nodes with Escherichia coli occurred in all rats treated with 10(5) IU of rIL-2, and in 62%, 37% and 12% of rats treated with decreasing doses of rIL-2. No translocation was observed in control animals. An increase in submucosal lymphatics and occasional mucosal disruption was seen only in the group receiving 10(5) IU. These data show that rIL-2 promotes bacterial translocation and suggests a mechanism that may fuel high-dose rIL-2 toxicity in man.

Failure of macrophage activation in experimental obstructive jaundice: association with bacterial translocation.

Bacterial translocation from the gastrointestinal tract and macrophage activation are central to current theories of sepsis. The relevance of both in obstructive jaundice is unclear. The effect of bile duct ligation for 7 days on bacterial translocation to mesenteric lymph nodes and on macrophage activation in a rat model was examined. Compared with an incidence of zero in sham-ligated controls, bile-duct ligated rats had a 67 per cent incidence of Gram-negative colonization of mesenteric lymph nodes. This was associated with a significant (P < 0.001) decrease in macrophage tumour necrosis factor, superoxide anion and nitric oxide production compared with that in sham controls. Spontaneous bacterial translocation occurs in experimental obstructive jaundice and is associated with marked suppression of macrophage activation. This suggests a mechanism whereby jaundiced patients may be more susceptible to persistent infection but relatively protected against uncontrolled sepsis.

Endothelium derived relaxing factor is absent in experimental in situ vein grafts.

Endothelium derived relaxing factor (EDRF) is a local modulator of vasomotor tone in most blood vessels. Reversed vein grafts in several animal models do not produce EDRF when stimulated, and have been shown to have altered responses to several vasoconstrictors. The preservation of EDRF production and vasomotor function in in situ vein grafts was examined in this study. In situ vein grafts of the right carotid artery were performed in five mongrel dogs using external jugular vein. The contralateral jugular vein was used as a control. The vessels were harvested after 6 weeks and rings from the central portion of each vessel studied in vitro in an organ bath. Following cumulative dose response curves to noradrenaline, the rings were precontracted with the estimated ED50 (50% effective dose) dose of noradrenaline, and cumulative doses of acetylcholine added to induce EDRF release. The vein grafts were hypersensitive to noradrenaline, the ED50 being reduced from 8.7 +/- 2.7 x 10(-7) M in the jugular veins to 1.7 +/- 0.7 x 10(-7) M in the vein grafts (p < 0.05). All of the jugular vein segments relaxed in response to acetylcholine with a mean maximal relaxation of 42 +/- 6% of precontraction. None of the vein graft segments relaxed in response to acetylcholine despite the presence of an intact endothelium on scanning electron microscopy, but did relax in response to calcium ionophore. The results indicate that in situ vein grafts, like reversed grafts, fail to produce EDRF in response to acetylcholine. The grafts are also hypersensitive to noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced endothelialization of expanded polytetrafluoroethylene grafts by fibroblast growth factor type 1 pretreatment.

BACKGROUND: Biomaterial pretreatment with endothelial cell mitogens may enhance endothelialization. METHODS: Modified fibrin glue (FG) containing 1 ng/cm2 recombinant 125I-labeled fibroblast growth factor type 1 (125I-FGF-1), 20 micrograms/cm2 heparin, 2.86 mg/cm2 fibrinogen, and 2.86 x 10(-2) units/cm2 thrombin was pressure perfused into expanded polytetrafluoroethylene (ePTFE) grafts. Grafts were interposed into infrarenal aortas of 24 New Zealand white rabbits and explanted after 0, 5, 30, and 60 minutes and 1, 7, 14, and 30 days. Residual radioactivity was determined by gamma-counting. Remaining 125I-FGF-1 is expressed as percent of value at time 0. To determine the effect of the FG/FGF-1 on graft healing, three groups of 50 x 4 mm 60 microns internodal-distance nonreinforced ePTFE grafts were implanted in the aortoiliac position of 12 dogs. Group I (n = 12) contained the complete modified FG, group II (n = 6) contained FG with heparin but no FGF-1, and group III (n = 6) contained untreated identical ePTFE. Tritiated thymidine (0.5 microCi/kg) was injected intramuscularly 10 hours before explantation after 7 and 28 days for light and electron microscopy and en face autoradiography. RESULTS: Retention of 125I-FGF-1 showed rapid initial loss (delta %/delta min = -24.1) followed by slow loss after 1 hour (delta %/delta min = -0.03), with 13.4% +/- 6.9% remaining at 1 week and 3.8% +/- 1.1% at 30 days. Every FG/FGF-1 graft at 28 days showed extensive capillary ingrowth and confluent endothelialized luminal surfaces, not seen in any specimen of the other two groups. Autoradiography revealed a significant increase (p less than 0.05) in 3H-thymidine incorporation in the FG/FGF-1 grafts at 28 days versus all groups as a function of time and graft treatment. CONCLUSIONS: Pressure perfusion of an FGF-1/FG suspension into 60 microns internodal-distance ePTFE grafts promotes endothelialization through capillary ingrowth and increased endothelial cell proliferation.

An audit of surgery for seventy-one primary parotid tumours.

Seventy-one consecutive patients who presented with lumps in the parotid gland over an eight year period (1981-1989) were analysed. Two-thirds of the patients presented with a history of swelling for over one year, while a quarter (24%) had a parotid mass for over five years at initial referral. The pathology of these masses was diverse, with pleomorphic adenoma being the commonest (64%). Superficial parotidectomy was the commonest procedure employed (50/71) with local excision being performed only in the initial part of our series (15/71). There were five cases of permanent facial palsy, four following radical resection for malignancy. Tumour recurrence rate was 2/15 (13%) in cases treated by local excision while none of the 50 patients treated by superficial parotidectomy had tumour recurrence at a mean follow-up of five years. Only three patients developed Frey's Syndrome. It is recommended that increased community awareness of early referral of a parotid mass is necessary, as surgical treatment in the form of superficial parotidectomy, which is the ideal procedure for such lumps, carries minimal morbidity when performed by a surgeon with a special interest in parotid surgery.

A safe new procedure for high-risk patients with symptomatic gallstones.

Cholecystectomy is associated with an appreciable mortality rate in elderly high-risk patients. Patients aged over 60 years with symptomatic gallstones, at high operative risk, underwent cholecystotomy under local anaesthesia through a 3-cm incision. Stones were removed and clearance was demonstrated endoscopically and by tube cholecystography. Catheter drainage was continued for 7 days until a further cholecystogram confirmed clearance. The procedure was attempted in 26 patients with concomitant cardiovascular, respiratory or malignant disease. Successful removal of all gallbladder stones was possible in 24 patients. Four patients had common bile duct stones demonstrated on cholecystography, all of which were successfully treated by endoscopic sphincterotomy. All patients are symptom-free at a mean follow-up of 36 weeks with no recurrent stones on ultrasonography.

Kinetics of collagen deposition within bioresorbable and nonresorbable vascular prostheses.

This study compares the kinetics of collagen deposition within the prosthesis/tissue complexes formed following implantation of either polyglactin 910 (PG910), polydioxanone (PDS), or Dacron prostheses into rabbit infrarenal aortas. The grafts were explanted in triplicate at 1, 3, and 12 months, and then processed for spectrophotometric hydroxyproline quantitation. A 2 mm longitudinal strip from each sample was processed for histologic evaluation by light and electron microscopy. Results showed more extensive collagen deposition within the prosthesis/tissue complexes of both PG910 and PDS continuing throughout 3 months, as compared to less collagen deposition in Dacron grafts at all time points. Differences between PG910 and Dacron, and between PDS and Dacron at each time point were statistically significant. When correlated with previous related studies done in our laboratory, data showed that in resorbable grafts the rate of collagen deposition parallels the kinetics of cellular proliferation, tissue thickening, and graft resorption.

A new technique for bilateral iliac vein and inferior vena cava reconstruction using reinforced polytetrafluoroethylene.

We report on the management of a patient with intractable venous claudication and ulceration due to bilateral iliac vein and inferior vena cava occlusion. An inverted V graft was constructed from two 8 mm diameter reinforced PTFE grafts. The upper end was anastomosed to the inferior infrarenal vena cava and the lower ends anastomosed to the common femoral veins. Bilateral arteriovenous fistulas were fashioned. Nine months later the graft is patent and the patient's only symptom is mild ankle edema. The theoretical advantage of this type of graft is that occlusion of one limb will not compromise the other, thus leaving a number of secondary options open if this should happen.