Does the angiotensin-converting enzyme (ACE) gene polymorphism affect rate of abdominal aortic aneurysm expansion?

OBJECTIVES: the tissue renin-angiotensin system (RAS), which plays an important role in vascular structure and function, is regulated in part by an insertion-deletion polymorphism of the angiotensin converting enzyme (ACE) gene. We hypothesised that ACE genotype might affect rate of AAA expansion via modulating long-term structural changes associated with RAS activation. METHODS: fifty-eight patients (50 M, mean age 70 years, mean initial aneurysm size 4.3 cm) with current or previous AAA and serial (>3) annual ultrasound measurements of antero-posterior AAA size provided a sample of leucocyte DNA for ACE genotyping. AAA expansion rate (cm per year) for individual subjects was calculated by linear regression. RESULTS: median AAA expansion rate was 0.28 cm/year (range 0-1.8 cm/year), and the genotype distribution included DD (n=14), DI (n=29) and II (n=15). Corresponding median AAA expansion rates for each of the three genetic subgroups were 0.22, 0.32 and 0.30 cm/year, respectively (p=0.6, nonparametric). CONCLUSIONS: the wide inter-individual variability in AAA expansion rate is likely to reflect complex genetic and environmental interactions, but the lack of any relationship with ACE genotype suggests that differences in vascular ACE activity in aortic tissue are not major determinants of the variability in rate of AAA dilatation.

Acquired abnormalities of the biliary tract from chronic gallstone disease.

BACKGROUND: Acquired abnormalities of the biliary tract from chronic gallstone disease are rare. The aim of this study was to examine the frequency with which these abnormalities occur and to assess the probability of encountering such an abnormality at laparoscopic cholecystectomy. STUDY DESIGN: We conducted a prospective study of all patients undergoing elective and emergency cholecystectomy under the care of one surgeon between January 1991 and December 1997. RESULTS: Biliary tract abnormalities from chronic gallstone disease were encountered in 10 (2%) of 486 patients undergoing cholecystectomy. Four were observed in patients undergoing elective laparoscopy cholecystectomy, and the remainder were observed at open cholecystectomy. Five had a cholecystocholedochal fistula (Mirizzi Syndrome Type II), and one had a stone impacted at the cystic duct-bile duct junction (Mirizzi Syndrome Type I). Two had cholecystoduodenal fistulas and two had an absent cystic duct with a normal bile duct. Both instances of an absent cystic duct were encountered at laparoscopic cholecystectomy; in one the bile duct was mistaken for the cystic duct and a 2-cm segment was excised at operation, and in the other the abnormality was recognized and confirmed by cholangiography. CONCLUSIONS: This study demonstrates a similar incidence of acquired abnormalities of the biliary tract from chronic gallstone disease to that already reported. But acquired absence of the cystic duct may occur more frequently than previously suspected. Patients with this condition are at high risk for bile duct injury during laparoscopic cholecystectomy. Clinical awareness of this problem with strict adherence to the principles taught at open cholecystectomy may prevent or reduce the severity of bile duct injury in these patients.

Intraoperative identification of sentinel lymph node in patients with malignant melanoma.

We report our experience with the technique of lymphatic mapping using patent blue V dye in patients with limb malignant melanoma. The technique is based on the hypothesis that embolic metastases occur along lymphatic channels to a 'sentinel' lymph node: the draining lymph node nearest the site of the primary malignant melanoma. Patent blue V dye (0.5-1.0 ml) is injected intradermally around the site of the melanoma. Immediately the groin or axilla is opened and the blue lymphatic channels followed to the sentinel node. The node is removed and examined by both haematoxylin and eosin (H&E) and immunohistochemical staining. We have carried out this technique in 35 patients, all of whom had 'clinically assessed' stage I disease. In all 35 patients, sentinel nodes were identified, and nine were found to contain unsuspected micrometastases. Our initial evaluation of intraoperative lymphatic mapping is very promising. The technique is practicable and easy to master. If 25% of patients with cutaneous malignant melanoma who are clinically stage I have nodal disease, this has great importance not only for staging and treatment but also for all future therapeutic trials.

A single centre's 10 year experience with isolated limb perfusion in the treatment of recurrent malignant melanoma of the limb.

The aim of this study was to assess whether isolated limb perfusion can be performed safely and whether it offers improved disease-free survival for patients with limb malignant melanoma. Between August 1983 and July 1993, 103 patients (78 female, 25 male) with recurrent limb melanoma were treated by isolated limb perfusion (ILP) in Glasgow, U.K. The mean age of the patients was 62 years; 95 had leg recurrence, 8 had arm recurrence. The mean time from original diagnosis to ILP was 48 months (range 1-290). 102 iliac, 5 femoral, 7 popliteal and 8 axillary perfusions were performed. All patients had stage II (local recurrence within 3 cm of primary site) or stage III (regional metastases; tissues excluding nodes, nodes or combination) disease according to the MD Anderson Cancer Centre Staging System. At a mean follow-up of 30.7 months, 68 patients had died of recurrent disease (mean time to death 22.5 months). The 2 and 5 year survival of the group was 50 and 26%, respectively and disease-free survival was 23 and 12%, respectively. At first perfusion, 76% of patients showed complete response and 23% showed partial response. With repeat perfusion, 47% showed complete response and 53% had partial response. In conclusion, ILP is safe and has an acceptable morbidity. It achieves highly satisfactory local disease control but long-term survival is the exception.

Single-centre prospective study of isolated limb perfusion with melphalan in the treatment of subungual malignant melanoma.

Subungual melanoma is rare and experience in treating this condition with isolated limb perfusion is limited. Between 1985 and 1990, 24 patients were treated by digital amputation and isolated limb perfusion with melphalan and mild hyperthermia. The disease was staged according to the M.D. Anderson classification: stage I (17 patients), stage IIIA (one), stage IIIB (two) and stage IIIAB (four). Thirteen lesions were on the foot and 11 on the hand. Seven patients have developed locoregional recurrence. The estimated overall 2- and 5-year probabilities of survival were 77 and 46 per cent respectively, while for disease-free survival the rates were 58 and 51 per cent. When these results were compared retrospectively with those in 111 patients treated by amputation alone, no significant difference in survival was demonstrated. This experience suggests that isolated limb perfusion with melphalan and mild hyperthermia confers no additional survival benefit over appropriate surgery.

Carbon dioxide laser ablation as an alternative treatment for cutaneous metastases from malignant melanoma.

Surgical excision of cutaneous malignant melanoma metastases is practical only when the number of lesions is small. In some patients isolated limb perfusion is not possible or fails to achieve control, and carbon dioxide laser ablation is then an alternative treatment. Between September 1992 and September 1994, 19 patients aged 45-94 years were treated with carbon dioxide laser. Two patients had received no previous limb perfusion, while the remaining 17 had up to three previous perfusions. The number of lesions per patient ranged from three to 40 nodules. A Sharplan 1030 portable carbon dioxide laser was used, which generates a beam wavelength of 10.6 microns and has a maximum power output of 80 W. All procedures were carried out under general anaesthesia. Each lesion was destroyed with a focused laser beam of 10-20 W with a spot size of 0.5-1.0 mm. At a mean follow-up of 15 months, five patients have died from the disease. Among the 14 survivors, eight have had no limb recurrence of the disease, three have had one further treatment and three a further two treatments to control cutaneous metastases at new sites. Early experience suggests that carbon dioxide laser ablation of cutaneous metastases is an effective palliative treatment after failed isolated limb perfusion, and there may be a group of patients in whom laser ablation should be the initial treatment of choice.

Subcutaneous urinary diversion: an alternative to percutaneous nephrostomy.

Nephrostomy has been the standard method of urinary diversion when placement of ureteral stents has failed in cancer patients. We describe our early experience with an alternative method of urinary diversion, the subcutaneous urinary diversion. This extra-anatomical urinary diversion was done in 5 patients during a 15-month interval. The diversion is created using a specially designed 7F double pigtail stent. The proximal end of the stent is inserted into the renal pelvis via a percutaneous nephrostomy puncture. A subcutaneous tunnel is created from the flank to the bladder down which the distal end of the stent is passed and via a suprapubic bladder puncture the stent is passed into the bladder. The stent is changed at 4-month intervals over a guide wire. Our early experience with this extra-anatomical method of urinary diversion suggests it to be a safe, effective and acceptable alternative to nephrostomy that improves quality of life.