Adrenocortical response and regional T-lymphocyte activation patterns following minimally invasive surgery in a rat model

Background: Laparoscopic surgery is associated with less tissue trauma and postoperative pain as well as a more rapid recovery than open surgery. We hypothesized that these factors may result in less immune impairment following laparoscopic surgery. Methods: We measured mitogen-induced surface interleukin-2 receptor (IL2R) expression and lymphocyte proliferation in CD4⁺ and CD8⁺ T-lymphocytes as well as serum corticosterone levels in rats 24 h following open (OP) and laparoscopic (LAP) fundoplication. Results: Serum corticosterone levels were lower in LAP vs OP rats (p= 0.02). CD4⁺ IL2R expression was higher in the blood, but not in the spleen, in LAP vs OP animals (p= 0.02). CD8⁺ IL2R expression was similar in both groups. Mitogen-induced lymphocyte proliferation was no different in the blood but decreased in the spleen in LAP vs OP rats (p= 0.03). Conclusions: Compared to open surgery, laparoscopic fundoplication in the rat results in lower adrenocortical hormone levels and better-preserved T-helper-cell activation in the blood. Lymphocyte proliferation is suppressed in the spleen 24 h after laparoscopic surgery. Minimally invasive surgery may better preserve cell-mediated immunity in the early postoperative period. Received: 2 April 1997/Accepted: 15 July 1997     

Laparoscopic repair of perforated duodenal ulcer

Background: A series of 100 consecutive patients with perforated peptic ulcer were prospectively evaluated in a multicenter study. The feasibility of the laparoscopic repair was evaluated. Methods: All patients had peritonitis, 20% were in septic shock, and 57% had delayed perforation. Conversion to laparotomy was necessary in eight patients. The morbidity rate was 9% and mortality rate 5%. Results: The mean delay of postoperative gastric aspiration (mean 3.4 days) and resumed food intake (mean 4.4 days) as well as the mean postoperative hospital stay (mean 9.3 days) were comparable to conventional surgery, but postoperative comfort was subjectively increased by laparoscopy and noticed by all laparoscopic surgeons participating in this study. Conclusions: Laparoscopic repair of perforated peptic ulcer proves to be technically feasable and carries an acceptable morbidity and mortality rate, compared with conventional surgery. Received: 16 August 1996/Accepted: 1 April 1997     

Surgical treatment of pheochromocytomas

Background: The use of minimally invasive techniques in the surgical treatment of pheochromocytoma is controversial because of possible intraoperative excessive hormone release resulting in cardiovascular instabilities. Methods: Laparoscopic adrenalectomy was performed in nine patients with a total of 10 pheochromocytomas. Conversion was required in two cases. The relevant data were prospectively documented and compared with a historical group of nine patients who had undergone conventional transabdominal adrenalectomy for unilateral pheochromocytoma. Results: The laparoscopic operations lasted significantly longer than the conventional procedures (median 243 min vs. 100 min, p < 0.01). Intraoperative cardiovascular instabilities (tachycardia, hypertension) occurred in seven laparoscopically and eight conventionally treated patients. All were easily controlled. Blood transfusions were necessary in four patients in the conventional and one patient in the laparoscopic group. Postoperative hospital stay and duration of analgetic treatment were significantly shorter after laparoscopic adrenalectomy. Conclusions: Laparoscopic adrenalectomy is a safe procedure for patients with pheochromocytoma. Received: 11 May 1997/Accepted: 20 March 1998     

Prospective, multicenter study of laparoscopic ventral hernioplasty

Background: A standard technique for laparoscopic ventral hernioplasty (peritoneal onlay using an expanded polytetrafluoroethylene [ePTFE] patch for hernias ≥4 cm²) is being used in a prospective, multicenter, long-term study. Methods: Demographic, operative, and postoperative data were collected and analyzed. Follow-up clinical evaluations were conducted 7–10 days, 4 weeks, 6 months, 1 year, and then annually after surgery in all patients. Results: In the first 2 years of the study, 144 patients were enrolled; nine were lost to follow-up. The mean operating time was 120 min. The mean follow-up was 222 days (range 5–731). Postoperative complications were five infections, three cases of prolonged ileus, one bowel obstruction, 23 seromas (15 resolved without intervention), and six hernia recurrences. Hospital discharge occurred a mean of 2.3 days after surgery and return to normal activity a mean of 15 days postoperatively. Conclusions: Laparoscopic prosthetic ventral hernioplasty avoids the large wound required in open repairs, with attendant complications and recurrences, and appears safe, especially if an ePTFE mesh is used. Compared with conventional open ventral hernioplasty, the laparoscopic technique may also allow shorter hospitalization and a quicker return to normal activities after surgery. Received: 3 April 1997/Accepted: 10 August 1997     

Laparoscopic gastro- and hepaticojejunostomy for palliation of pancreatic cancer

Background: Most patients presenting with pancreatic cancer are irresectable at the time the diagnosis is made. Therefore, they are in need of palliative treatment that can guarantee minimal morbidity, mortality, and hospital stay. To address this need, we designed a study to test the feasibility of laparoscopic gastroenterostomy and hepaticojejunostomy and to compare their results with those achieved with open techniques. Methods: We performed a case control study of a new concept in laparoscopic palliation based on the findings of preoperative imaging and diagnostic laparoscopy. Laparoscopic side-to-side gastroenterostomy and end-to-side hepaticojejunostomy (Roux-en-Y) were done in irresectable cases. Of 14 patients who underwent laparoscopic palliation, three had a laparoscopic double bypass, seven had a gastroenterostomy, and four underwent staging laparoscopy only. The results were compared with a population of 14 matched patients who had conventional palliative procedures. Results: Postoperative morbidity was 7% vs 43% for laparoscopic and open palliation, respectively (p < 0.05). There were no mortalities in the laparoscopic group, as compared to 29% in the group who had open bypass surgery (p < 0.05). Postoperative hospital stay averaged 9 days in the laparoscopic group and 21 days in the open group (p < 0.06). Operating time tended to be shorter in the laparoscopic group (p < 0.25). Morphine derivatives were necessary for a significantly shorter period after laparoscopic surgery (p < 0.03). Conclusions: Our preliminary experience strongly suggests that laparoscopic palliation can reduce the three major drawbacks of open bypass surgery—i.e., high morbidity, high mortality, and long hospital stay. Received: 24 February 1999/Accepted: 13 May 1999     

Laparoscopic vs conventional Nissen fundoplication

Background: Laparoscopic Nissen fundoplication has gained wide acceptance among surgeons, but the results of the laparoscopic procedure have not been compared to the results of an open fundoplication in a randomized study. Methods: Some 110 consecutive patients with prolonged symptoms of grade II–IV esophagitis were randomized, 55 to laparoscopic (LAP) and 55 to an open (OPEN) Nissen fundoplication. Postoperative recovery, complications, and outcome at 3- and 12-month follow-up were compared in the two groups. Results: Five LAP operations were converted to open laparotomy due to esophageal perforation (two), technical difficulties (two), and bleeding (one). In the OPEN group (two) patients underwent splenectomy. There was no mortality. The mean hospital stay was 3.2 days in the LAP group and 6.4 in the OPEN group. Dysphagia and gas bloating were the most common complaints 3 months after the operation in both groups. These symptoms had disappeared at the 12-month follow-up examination. All patients in the LAP group and 86% in the OPEN group were satisfied with the result. Conclusions: Laparoscopic Nissen fundoplication is a safe and feasible procedure. Complications are few and functional results are good if not better than those of conventional open surgery. Received: 15 May 1996/Accepted: 10 September 1996     

Cosmesis and body image after laparoscopic-assisted and open ileocolic resection for Crohn's disease

Background: The objectives of this study were to evaluate body image, cosmetic results, and quality of life in patients with Crohn's disease of the terminal ileum who had either laparoscopic-assisted or open ileocolic resection, and to determine how patients experienced the pre- and postoperative periods after both procedures. Methods: Thirty-four patients participated: 11 patients after open resection (OR), 11 patients after laparoscopic-assisted resection (LR), and 12 patients without resection (WR). Retrospectively, the patients filled out several questionnaires pertaining to body image, hospital experiences, and quality of life. One-way analysis of variance, Student's t-tests, and Pearson's correlation were used for statistical analysis. Results: The cosmetic score was significantly higher in the LR than in the OR group (p < 0.01). Body image correlated strongly with cosmesis and with quality of life. The hospital experiences of the laparoscopic and open groups were similar. Conclusions: Laparoscopic surgery was associated with better cosmesis than open surgery. Patients do not experience laparoscopic surgery any differently from open surgery. Received: 29 September 1997/Accepted: 21 January 1998     

Laparoscopic treatment vs open surgery in the solution of major incisional and abdominal wall hernias with mesh

Background: Despite being one of the most exact indications, laparoscopic treatment of eventrations and ventral hernias is barely known among the array of laparoscopic techniques. Methods: A total of 60 patients were assigned at random over a 3-year period to two homogeneous groups to be operated on for major ventral hernias with mesh. Half of them were operated upon laparoscopically and the rest with open surgery. Early and longer-term complications were analyzed, as were operative time and postoperative hospital stays. Results: The two groups were homogeneous in terms of demographic and clinical characteristics. The group that was operated on laparoscopically presented a lower rate of postoperative and longer-term complications; similarly, surgery time was significantly lower (p < 0.05). Hospitalization time was also significantly lower than in the group undergoing conventional open surgery (p < 0.05). Conclusions: Laparoscopic treatment of postoperative eventration and primary ventral hernia reduces complications and relapse rates, eliminates reintervention through mesh infection, reduces operative time, and considerably shortens the hospital stay. Received: 22 December 1997/Accepted: 18 August 1998     

Effect of surgical stress on endogenous morphine and cytokine levels in the plasma after laparoscopoic or open cholecystectomy

Background: Endogenous morphine in the brain leads to various biological responses after surgery. The aim of this study was to determine whether morphine levels in the plasma would be enhanced by open laparotomy rather than by laparoscopic procedures. Methods: We compared 19 patients who underwent laparoscopic cholecystectomy with five patients who underwent resection of the gallbladder by open laparotomy. Morphine levels in the plasma were measured by an electrochemical detection system. Results: Postoperative endogenous morphine levels were higher with open laparotomy than with the laparoscopic technique (three h after surgery: open, 200 ± 52.6 fmol/ml vs laparoscopy, 17.6 ± 3.7, p < 0.01). This morphine elevation accounted for higher levels of cytokine, greater pain scores, and longer duration of fasting in open laparotomized patients than in laparoscopic cholecystectomy patients. Stress hormone levels in the plasma were also higher with open laparotomy than with laparoscopy. Conclusion: Morphine synthesis was enhanced by open laparotomy, resulting in greater biological response postoperatively than that seen with laparoscopic cholecystectomy. Received: 21 October 1998/Accepted: 3 April 1999     

Laparoscopic surgery during pregnancy

Background: Laparoscopic surgery is known for its many advantages, but the use of this modality during pregnancy is still under discussion. Methods: The subjects in this discussion are the unknown influence of the pneumoperitoneum and the fear of damaging the uterus while inserting the Veress needle and trocars. In a review of recent literature describing laparoscopic surgery during pregnancy, no complications were seen. We performed four laparoscopic appendectomies and three laparoscopic cholecystectomies between 12 and 33 weeks estimated gestational age (EGA). Results: All pregnancies passed without complications and ended in at-term deliveries of healthy babies. Conclusions: The risks, precautions to avoid them, and the safety of laparoscopic surgery during pregnancy are discussed in the light of our experience and reports in recent literature. Received: 26 September 1995/Accepted 3 May 1996     

Laparoscopic surgery preserves monocyte-mediated tumor cell killing in contrast to the conventional approach

Background: Experimental animal research shows that immunologic defenses against tumor cells are disturbed by surgical trauma, resulting in an increased rate of tumor implantation and the growth of subsequent metastases. Minimally invasive surgery is associated with a preservation of postoperative immunologic functions and, in animal models, with decreased tumor growth. The objective was to study the influence of several surgical procedures, approached conventionally and laparoscopically, on interleukin-6 (IL-6) and monocyte-mediated cytotoxicity (MMC). Methods: Five groups of five patients each were included in this prospective study: laparoscopic cholecystectomy (minor trauma) group, Nissen fundoplication (laparoscopic and conventional as moderate trauma) groups, and sigmoid colectomy (laparoscopic and conventional as major trauma) groups. Preoperatively, 1 and 4 days after surgery, IL-6 and MMC against SW948 colon cancer cell line were determined. Results: The IL-6 levels differed significantly between the three laparoscopic procedures (p= 0.004) and increased according to the degree of trauma. There was no significant difference in MMC between the three laparoscopic procedures. However, MMC was suppressed after conventional procedures and preserved after laparoscopic procedures (p= 0.001). There was no correlation between IL-6 levels and changes in MMC. Conclusions: More extensive laparoscopic procedures induce increased levels of IL-6, reflecting higher levels of trauma. Conventional surgical procedures result in depressed MMC in the postoperative period. After laparoscopic procedures, MMC is preserved. These findings may be of importance in preventing implantation and growth of cancer cells spread by surgical manipulation. Received: 10 December 1998/Accepted: 25 March 1999     

Postoperative pain and fatigue after laparoscopic or conventional colorectal resections

Background: Conventional colorectal resections are associated with severe postoperative pain and prolonged fatigue. The laparoscopic approach to colorectal tumors may result in less pain as well as less fatigue, and may improve postoperative recovery after colorectal resections. Methods: Sixty patients were included into a prospective randomized trial to determine the influence of laparoscopic (n= 30) or conventional (n= 30) resection of colorectal tumors on postoperative pain and fatigue. Major endpoints of the study were dose of morphine sulfate during patient-controlled analgesia (PCA), visual analog scale for pain while coughing (VASC), and visual analogue scale for fatigue (VASF). Efficacy of pain medication was assessed by visual analogue score at rest (VASR). Results: Preoperative age, sex, stage, and localization of tumors were comparable in both groups. The PCA dose of morphine given immediately after surgery until postoperative day 4 was higher in the conventional group (median, 1.37 mg/kg; 5–95 percentile 0.71–2.46 mg/kg) than the laparoscopic group (0.78 mg/kg; 0.24–2.38 mg/kg, p < 0.01). Postoperative VASR was comparable between both groups, but VASC was higher from the first to the seventh postoperative day (p < 0.01). Postoperative fatigue was higher after conventional than after laparoscopic surgery from the second to the seventh day (p < 0.05). Conclusions: This study confirms that analgetic requirements are lower and pain is less intense after laparoscopic than after conventional colorectal resection. Patients also experience less fatigue after minimal invasive surgery. Because of these differences, the duration of recovery is shortened, and the postoperative quality of life is improved after laparoscopic colorectal resections. Received: 4 July 1997/Accepted: 16 November 1997     

Laparoscopic cecal ligation and puncture in the rat

Background: We describe a technique of laparoscopic cecal ligation and puncture (CLP) in the rat analogous to open CLP which may facilitate the study of minimally invasive surgery (MIS) and peritonitis. Methods: Forty-four rats were randomized to either laparoscopic or open CLP and their 3-day mortality was recorded. Autopsies were performed for peritoneal fluid cultures, measurement of the length of ligated cecum, and scoring of the degree of cecal necrosis. Results: Laparoscopic CLP required slightly longer operating times compared to open CLP (average 15.6 vs 13.1 min, p= 0.002). Three-day postoperative mortality was 36.4% and 22.7% for open and laparoscopic CLP, respectively (p= NS). There were no differences in the length of ligated cecum or the cecal necrosis score between the open and laparoscopic CLP groups. Conclusion: Laparoscopic CLP is feasible and produces a fecal peritonitis with similar characteristics to those of traditional open CLP. Received: 3 July 1996/Accepted: 7 January 1997     

Lack of neurohumoral response to pneumoperitoneum for laparoscopic cholecystectomy

Background: Pneumoperitoneum (PP) for laparoscopic surgery induces prompt changes in circulatory parameters. The rapid onset of these changes suggests a reflex origin, and the present study was undertaken to evaluate whether release of vasopressor substances could be responsible for these alterations. The influence of two different anesthesia techniques was also evaluated. Methods: American Society of Anesthesiologists (ASA) class I patients, scheduled for laparoscopic cholecystectomy, were investigated. The first group (n= 10) was anesthetized intravenously. The second group (n= 6) had inhalation anesthesia. Plasma vasopressin, catecholamines, and plasma renin activity were investigated as neurohumoral vasopressor markers of circulatory stress. The general stress response to surgery was assessed by analysis of plasma cortisol. Results: Induction of pneumoperitoneum caused no apparent activation of vasopressor substances, although several hemodynamic parameters responded promptly. Conclusion: The hemodynamic alterations, seen at the establishment of PP during stable anesthesia, cannot be explained by elevation of vasopressor substances in circulating blood. Received: 7 April 1997/Accepted: 3 December 1997     

Successfully establishing laparoscopic surgery programs in developing countries

Background: Laparoscopic surgery has not been widely established in developing countries due to the lack of access to training and lack of money. We describe our experience using on-site training programs to efficiently teach and propagate laparoscopic surgery in Leon, Nicaragua; La Paz, Bolivia; and Santa Cruz, Bolivia. Methods: A group of well-trained and motivated local surgeons was identified in each country as the initial target for teaching. Participants were taught basic and advanced laparoscopic surgery during on-site didactics, animal laboratories, and proctoring sessions. Follow-up courses were held until the target group of surgeons was capable of independently teaching and supervising laparoscopic surgery among other surgeons in each country. Results: Multiple technical and logistic difficulties were encountered. In Leon, Nicaragua, and La Paz, Bolivia, a total of eight surgeons were fully trained and proctored in laparoscopic cholecystectomy. In La Paz and Santa Cruz, Bolivia, a total of seven surgeons were instructed in advanced laparoscopic procedures. To date, over 180 patients have undergone laparoscopic cholecystectomy or advanced procedures with a morbidity similar to that reported in literature series in the United States. Conclusions: Our experience demonstrates that in spite of numerous limitations, basic and laparoscopic surgery can be efficiently and safely taught in developing countries. Many lessons were learned in how to safely and efficiently use laparoscopic equipment and instruments within strict financial constraints. Received: 20 March 1996/Accepted: 15 May 1996     

The impact of a full-time director of minimally invasive surgery

Background: One of the biggest challenges of the laparoscopic surgery revolution is resident training. To enhance resident training, some programs have hired an experienced laparoscopic surgeon. This study documents the impact of this addition to our training program. Methods: The number and types of laparoscopic cases, the number of laparoscopic training sessions, and the number of minimally invasive research projects were tabulated for 12-month periods before (period 1) and after (period 2) the arrival of the laparoscopic surgeon. Results: Laparoscopic procedures increased from 524 (period 1) to 1,077 (period 2). Advanced procedures increased from 213 to 629. Laparoscopic training sessions increased from 2 to 11, and approved minimally invasive research projects increased from 0 to 7. Conclusions: The addition of an experienced laparoscopic surgeon in a resident training program increased laparoscopic cases in which the residents participate by more than 100%. Laparoscopic training sessions and minimally invasive research projects also increased measurably. Received: 22 January 1999/Accepted: 17 June 1999     

Laparoscopic treatment of lymphocele after kidney transplantation

Background: Laparoscopic treatment of pelvic lymphocele secondary to kidney transplant has gained popularity in the last few years, although lesions of the urinary tract (ureter, renal pelvis, and bladder) have been reported frequently. To evaluate the result of this treatment and the associated risk of urinary tract lesions, we reviewed our experience and reports in the medical literature on open and laparoscopic surgery. Methods: From 1991 to 1999, we laparoscopically treated 12 patients (7 men and 5 women; median age, 43 years; range, 17–59 years) with symptomatic pelvic lymphocele causing a deterioration of renal function because of compression on the ureter in 10 of the 12 patients and lymphocele compression of the iliac vein in the other 2 patients. In nine patients, the lymphocele wall was opened and sutured to the peritoneum to keep the window open. In two patients, an omentoplasty was performed, and in the remaining patient, both techniques were used. All patients were followed up clinically with ultrasound and biochemistry for a median period of 33 months (range, 1–96 months). Using Medline, we reviewed the medical literature from 1980 to 1998 and collected 252 cases in which operations had been performed to drain an internal lymphocele secondary to kidney transplantation. Results: Laparoscopic treatment was successful in 11 of the 12 patients. One patient was converted to open surgery because of a lesion in the transplanted ureter. One patient needed repeat laparoscopy 24 hours after the operation because of bleeding from the peritoneal window. The median duration of the operation was 120 min (range, 70–200 min), and the median postoperative hospital stay was 5 days (range, 2–12 days). None of the patients needed to discontinue oral cyclosporine assumption. The serum creatinine level dropped significantly after surgery (p < 0.05). No symptomatic recurrences were observed. Of the 252 patients found in the medical literature, in 129 the procedure was performed with open surgery and in 123 laparoscopically (our 12 patients included). The prevalence of iatrogenic lesions to the urinary tract increased threefold with the use of laparoscopic surgery (from 1.6% in open surgery to 7% in laparoscopy). The recurrence rate of symptomatic lymphocele, however, decreased from 15% to 4%. Conclusions: Laparoscopic drainage of posttransplantation lymphocele is a relatively simple method for treating this complication, although it bears the burden of an increased incidence of urinary tract lesions, as confirmed by a review of the literature. The major advantage of the laparoscopic approach is the absence of postoperative ileus with the opportunity to continue the enteral immunosuppressive regimen and a lower recurrence rate. These data suggest that laparoscopic lymphocele treatment might be considered the therapy of choice, provided the iatrogenic lesions of the urinary tract diminish as more experience with this technique is gained. Received: 1 March 1999/Accepted: 1 July 1999     

Laparoscopic end-to-end aortobifemoral bypass with reimplantation of the inferior mesenteric artery

Background: Colic ischemia is a serious complication that can occur after abdominal aortic surgery. It has been described in two patients after laparoscopic aortic surgery. The goal of the current experiment was to determine the feasibility of inferior mesenteric artery (IMA) reimplantation during laparoscopic aortobifemoral bypass (LAFB). Methods: Six piglets were submitted to the laparoscopic approach according to the ``apron' technique previously described. The infrarenal aorta was clamped and an LAFB was performed using a dacron graft. The IMA was reimplanted in the body of the graft with a running 5-0 polypropylene suture. Results: Mean operation and dissection times were 282.5 min (range, 270–310 min) and 123 min (range, 110–140 min), respectively, with a mean blood loss of 108 ml (range, 80–150 ml). Aortic clamping and anastomotic times were 123 min (range, 110–135 min) and 33 min (range, 24–45 min), respectively. The IMA reimplantation took 55 min (range, 45–70 min). At autopsy, all anastomoses were patent with no stenosis nor leak. Conclusion: Laparoscopic IMA reimplantation during laparoscopic aortobifemoral bypass is feasible. Received: 10 July 1998/Accepted: 15 November 1998     

Technical advances toward interactive image-guided laparoscopic surgery

Background: Laparoscopic surgery uses real-time video to display the operative field. Interactive image-guided surgery (IIGS) is the real-time display of surgical instrument location on corresponding computed tomography (CT) scans or magnetic resonance images (MRI). We hypothesize that laparoscopic IIGS technologies can be combined to offer guidance for general surgery and, in particular, hepatic procedures. Tumor information determined from CT imaging can be overlayed onto laparoscopic video imaging to allow more precise resection or ablation. Methods: We mapped three-dimensional (3D) physical space to 2D laparoscopic video space using a common mathematical formula. Inherent distortions present in the video images were quantified and then corrected to determine their effect on this 3D to 2D mapping. Results: Errors in mapping 3D physical space to 2D video image space ranged from 0.65 to 2.75 mm. Conclusions: Laparoscopic IIGS allows accurate (<3.0 mm) confirmation of 3D physical space points on video images. This in combination with accurately tracked instruments and an appropriate display may facilitate enhanced image guidance during laparoscopy. Received: 30 April 1999/Accepted: 10 November 1999/Online publication: 8 May 2000     

Laparoscopic interval appendectomy for periappendicular abscess

Background: Laparoscopic appendectomy was first described in the early 1980s and is currently widely used for the treatment of acute appendicitis. The application of laparoscopic techniques to interval appendectomy and the value of this procedure as compared to open elective interval appendectomy remains uncertain. Therefore, we set out to assess the usefulness of interval laparoscopic appendectomy following periappendicular abscess. Methods: This study analyzes the data for 10 patients who underwent interval laparoscopic appendectomy 8–10 weeks following documented periappendicular abscess in the period between January 1996 and June 1998. Results: Laparoscopic appendectomy was completed successfully in all 10 patients. Nine patients were discharged 1 day after the operation; one patient was discharged on the evening of the operative day. There were no complications and no wound infections. Conclusion: We conclude that the laparoscopic approach is the preferable treatment for interval appendectomy. It is associated with minimal or no morbidity and a very short hospital stay. Received: 13 May 1999/Accepted: 9 December 1999/Online publication: 12 July 2000