Preoperatively determinable factors predictive of diabetes mellitus remission following Roux-en-Y gastric bypass: a review of the literature.

It is well established that weight loss in general and bariatric surgery in particular can improve glycaemic control in diabetics. Current NICE guidelines recommend that those patients with type 2 diabetes mellitus and a BMI of 35 kg/m(2) or more should be considered for bariatric surgery in order to optimise their glycaemic control and minimise their risk of long-term complications. The commonest bariatric procedure in the UK is the Roux-en-Y gastric bypass that has been shown to result in long-standing type 2 diabetes resolution in 83 % of patients. Since such surgery carries a small but significant risk of mortality, as well as posing considerable lifestyle implications for the patient, numerous studies have been performed with a view to identifying which patients and which procedures are most likely to result in these desired benefits. This paper summarises the existing literature on this topic.

Predictors for acute and chronic pouchitis following restorative proctocolectomy for ulcerative colitis.

OBJECTIVE: This study was undertaken to evaluate the cumulative incidence, onset and risk predicting factors for acute and chronic pouchitis. METHOD: A consecutive series of patients (n = 210), who underwent restorative proctocolectomy (RPC) and had a minimum follow-up of 12 months was reviewed. The cumulative incidence and onset of pouchitis was determined. Univariate analysis, followed by logistic regression analysis was used to evaluate the association of various demographic, clinical and histopathologic variables with the subsequent development of acute and chronic pouchitis. RESULTS: A total of 198 patients were included. The mean follow-up was 64 months (range, 12-180). Sixty-four patients (32%) developed pouchitis, 35 acute and 29 chronic. The first episode of pouchitis occurred within the first year in 70% of cases. The presence of backwash ileitis (OR, 2.6; P = 0.015), primary sclerosing cholangitis (PSC; OR, 2; P = 0.018) and the duration of follow-up (OR, 1.1; P = 0.043) were associated with a higher incidence of pouchitis. The duration of follow-up was the only variable associated with acute pouchitis (P = 0.007). The presence of backwash ileitis and PSC were independent risk factors for chronic pouchitis (OR, 5.9; P < 0.001; OR, 2.8; P = 0.001 respectively). CONCLUSION: Pouchitis is a heterogeneous disease which tends to occur early after restoration of gastrointestinal continuity. Patients with backwash ileitis and/or PSC are at considerable risk of developing chronic pouchitis. The strong association between backwash ileitis, PSC and chronic pouchitis suggests a common link in their pathogenesis.

Early symptomatic recurrence after intestinal resection in Crohn's disease is unpredictable.

OBJECTIVE: To identify predictors of early symptomatic recurrence of Crohn's disease (CD) after surgical resection. METHOD: We studied a cohort of 128 patients who had undergone at least one intestinal resection for CD. Factors that might predict early recurrence were documented for analysis using a standardized pro forma. These comprised age, gender, family history, extra-intestinal manifestations, smoking, complicated disease at first presentation, site of disease, preoperative inflammatory markers, involvement of resection margins, orientation and method of anastomosis and postoperative medical therapy. All symptomatic recurrences were confirmed by endoscopic, radiological, or operative means. We defined early recurrence as that which occurred within 36 months of first surgery. Univariate analysis was conducted to compare the distribution of each factor in those who developed early recurrence (n = 48) and those who remained disease free for the first 36 months (n = 50). RESULTS: Of the 128 patients studied, 98 fulfilled the inclusion criteria of at least 36 months of follow up. Of these patients, 48 (49%) patients developed recurrence. Trends towards fewer early recurrences were seen in patients with colonic disease (33%vs 56%, P = 0.068). Of the current smokers, 60% developed early recurrence compared with 43% of nonsmokers (P = 0.269). All other factors examined were similarly distributed between the two groups. Metronidazole as adjuvant treatment does not appear to protect against early symptomatic recurrence. CONCLUSION: This study shows that early symptomatic postoperative recurrence of CD remains unpredictable. Against expectation, abstinence from smoking and postoperative adjuvant metronidazole did not appear to protect against early symptomatic recurrence.

Rifaximin-ciprofloxacin combination therapy is effective in chronic active refractory pouchitis.

OBJECTIVE: Treatment of chronic refractory pouchitis is often difficult and disappointing and some of the affected pouches subsequently fail. This study was conducted to evaluate the efficacy and tolerability of treatment with rifaximin, a nonabsorbable oral antibiotic with immunomdulatory functions, in combination with ciprofloxacin for chronic active refractory pouchitis. PATIENTS AND METHODS: Eight patients with chronic active refractory pouchitis were treated orally with a combination of rifaximin 1 g b.d and ciprofloxacin 500 mg b.d. for two weeks. Clinical assessment, endoscopic and histological evaluations were performed before and after therapy using the Pouchitis Disease Activity Index (PDAI) score. Improvement was defined as a decrease of at least three points in the PDAI score and remission as a PDAI score of 0. The Wilcoxon signed rank test was used to compare pre- and post-treatment PDAI scores. The long-term outcome of the treated patients was prospectively monitored. RESULTS: Seven of the eight patients either went into remission (n = 5) or improved (n = 2). The median (range) PDAI scores before and after therapy were 12 (9-18) and 0 (0-15), respectively, (P = 0.018). All patients were compliant and no side effects were reported. Pouchitis recurred in two of the seven responding patients but returned into remission after further courses of the same combination. After a median follow-up of 30 months, the seven responding patients still had satisfactory pouch function. CONCLUSION: Rifaximin-ciprofloxacin combination therapy is safe and objectively effective in chronic active refractory pouchitis and may salvage a significant percentage of 'at risk pouches'.

The formation of AFB(1)-macromolecular adducts in rats and humans at dietary levels of exposure.

The levels of aflatoxin B(1)-DNA and aflatoxin B(1)-albumin adducts were investigated by accelerator mass spectrometry (AMS) in humans and rats following exposure to a known, dietary relevant amount of carbon-14 labeled aflatoxin B(1) ([(14)C]AFB(1)). The aims of the study were to: (a) investigate the dose-dependent formation of DNA and protein adducts at very low doses of AFB(1) (0.16 ng/kg-12.3 microg/kg) in the rat; (b) measure the levels of AFB(1)-albumin and AFB(1)-DNA adducts at known, relevant exposures in humans (c) study rat to human extrapolations of AFB(1)-albumin and DNA adduct levels. The results in the rat showed that both AFB(1)-albumin adduct and AFB(1)-DNA adduct formation were linear over this wide dose range. The order of adduct formation within the tissues studied was liver>kidney>colon>lung=spleen. Consenting volunteers received 1 microg ( approximately 15 ng/kg) of [(14)C]AFB(1) in a capsule approximately approximately 3.5-7 h prior to undergoing colon surgery. The mean level of human AFB(1)-albumin adducts was 38.8+/-19.55 pg [(14)C]AFB(1)/mg albumin/microg AFB(1)/kg body weight (b.w.), which was not statistically different to the equivalent dose in the rat (15 ng/kg) 42.29+/-7.13 pg [(14)C]AFB(1)/mg albumin/microg AFB(1)/kg b.w. There was evidence to suggest the formation of AFB(1)-DNA adducts in the human colon at very low doses. Comparison of the linear regressions of hepatic AFB(1)-DNA adduct and AFB(1)-albumin adduct levels in rat found them to be statistically similar suggesting that the level of AFB(1)-albumin adducts are useful biomarkers for AFB(1) dosimetry and may reflect the DNA adduct levels in the target tissue. [(14)C]AFB(1)-DNA and [(14)C]AFB(1)-albumin adducts were hydrolysed and analysed by HPLC to confirm that the [(14)C] measured by AMS was derived from the expected [(14)C]AFB(1) adducts.

Spontaneous dissection of the abdominal aorta.

Acute dissection of the aorta is a vascular surgical emergency. The majority of dissections originate in the thoracic aorta. Dissection originating in the infrarenal abdominal aorta is very rare and, given the vagueness of presenting symptoms of uncomplicated dissection, diagnosis is very difficult in the early stages. In the absence of a pulsatile abdominal mass, acute uncomplicated aortic dissection should be considered in the differential diagnosis of sudden onset of abdominal and back pain. We report a case of spontaneous infrarenal abdominal aortic dissection occurring in an ostensibly normal aorta, and discuss the diagnostic dilemma and subsequent management of the patient.

Comparative biotransformation studies of MeIQx and PhIP in animal models and humans.

MeIQx and PhIP are putative carcinogenic heterocyclic amines formed during the cooking of meat and fish. Using accelerator mass spectrometry, we have investigated the metabolism and macromolecule binding of 14C-labelled MeIQx and PhIP in human cancer patients compared to the rat. Following oral administration of MeIQx and PhIP, more DNA adducts were formed in human colon tissue compared with rats. Differences were also observed between rats and humans in the metabolite profile and urine excretion for these compounds. These results suggest humans metabolise heterocyclic amines differently to laboratory rodents and question their use as models of human risk.

Comparison of DNA-adduct and tissue-available dose levels of MeIQx in human and rodent colon following administration of a very low dose.

[2-14C]2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was administered orally (304 ng/kg body-weight dose based upon an average 70-kg-body-weight subject) to 5 human colon-cancer patients (58 to 84 years old), as well as to F344 rats and B6C3F1 mice. Colon tissue was collected from the human subjects at surgery and from the rodents 3.5 to 6 hr after administration. Colon DNA-adduct levels and tissue available doses were measured by accelerator mass spectrometry (AMS). The mean levels of MeIQx in the histologically normal colon tissue were not different among the human (97 +/- 26 pg MeIQx/g), rat (133 +/- 15 pg/g) or mouse (78 +/- 10 pg/g) tissues; and no difference existed between the levels detected in human normal and tumor tissue (101 +/- 15 pg/g). Mean DNA-adduct levels in normal human colon (26 +/- 4 adducts/10(12) nucleotides) were significantly greater (p < 0.01) than in rats (17.1 +/- 1 adduct/10(12) nucleotides) or mice (20.6 +/- 0.9 adduct/10(12) nucleotides). No difference existed in adduct levels between normal and tumor tissue in humans. These results show that MeIQx forms DNA adducts in human colon at low dose, and that the human colon may be more sensitive to the effects of MeIQx than that of mice or rats.

Metabolism of the food-borne mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in humans.

The metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was investigated in five human volunteers given a dietary equivalent of 14C-labeled MeIQx. The amount of the dose excreted in urine ranged from 20.2% to 58.6%, with unmetabolized MeIQx accounting for 0.7-2.8% of the dose. Five principal metabolites were detected in urine, and four of the derivatives were characterized by on-line UV spectroscopy and by HPLC-MS following immunoaffinity chromatography. Two metabolites were identified as the phase II conjugates N2-(3,8-dimethylimidazo[4,5-f]quinoxalin-2-yl)sulfamic acid (MeIQx-N2-SO3(-)) and N2-(beta-1-glucosiduronyl)-2-amino-3,8-dimethylimidazo[4,5-f ]quinoxaline (MeIQx-N2-Gl). Two other metabolites were the cytochrome P450-mediated (P450) oxidation products 2-amino-8-(hydroxymethyl)-3-methylimidazo[4,5-f]quinoxaline (8-CH2OH-MeIQx), and N2-(beta-1-glucosiduronyl)-N-hydroxy-2-amino-3,8-dimethylimidaz o[4,5-f]quinoxaline (NOH-MeIQx-N2-Gl). The latter product is a conjugate of the genotoxic metabolite 2-(hydroxyamino)-3,8-dimethylimidazo-[4,5-f]quinoxaline (NHOH-MeIQx). A large interindividual variation was observed in the metabolism and disposition of MeIQx; these four metabolites and unchanged MeIQx combined accounted for 6.3-26.7% of the total dose. The remaining principal metabolite found in all subjects accounted for 7.6-28% of the dose. It has not been previously identified in rodents or nonhuman primates, and its structure remains unknown. P450-mediated ring oxidation of MeIQx at the C-5 position, a major pathway of detoxication in rodents, was not detected in humans. Both 8-CH2OH-MeIQx formation and NHOH-MeIQx formation are catalyzed by P450 1A2 and may be useful biomarkers of P450 1A2 activity in humans. The levels of NHOH-MeIQx-N2-Gl found in human urine ranged from 1.4% to 10.0% of the dose, which is significantly higher than that formed in rodents and nonhuman primates undergoing cancer bioassays. Thus, bioactivation of MeIQx by P450-mediated N-oxidation is extensive in humans.

Limited role for intraoperative intact PTH measurement in parathyroid surgery.

Primary hyperparathyroidism may be cured surgically by complete excision of abnormal parathyroid tissue. Reoperation for persistent hypercalcaemia due to residual abnormal parathyroid tissue may be associated with a high complication rate. It is possible to assay intact parathormone (iPTH) intraoperatively and as iPTH has a relatively short half-life, its measurement intraoperatively may be used to predict successful parathyroidectomy. We have studied intraoperative iPTH levels in a consecutive series of 33 patients undergoing surgery for primary hyperparathyroidism. We found that iPTH levels fell significantly (P < 0.05) from a median pre-excision level of 122 pg/ml to a median level of 36 pg/ml 20 min after excision. However, in 3/31 successful parathyroidectomies, the intraoperative iPTH levels either remained unchanged or had risen. Reliance on intraoperative iPTH levels in these patients may have resulted in unnecessary re-exploration. We conclude that intraoperative iPTH measurement has limited usefulness as a predictor of successful parathyroidectomy for primary hyperparathyroidism.

Low frequency and late occurrence of p53 and dcc aberrations in colorectal tumours.

Whilst p53 aberrations have been documented in numerous malignancies, reports of alterations to the deleted in colorectal cancer (dcc) gene are infrequent, and studies investigating the status of both genes in the same colon tumour are rare. In this study we have analysed a panel of 35 pairs of normal and neoplastic human colorectal tissues for abnormalities in these tumour-suppressor genes. In contrast to previous studies we have found only a low incidence of mutations and deletions. p53 point mutations were identified in 8/35 tumours (22%). All were G.C to A.T transitions, with 7/8 occurring at CpG dinucleotides. p53 allelic loss was detected in 4/11 informative cases (36%). Although not quite attaining statistical significance, p53 alteration correlated with the adenoma/carcinoma transition. Gross dcc alterations were identified by Southern blotting in 7/35 (20%) tumours. Microsatellite analysis using two markers, one within and one proximal to the dcc gene, detected a low frequency of deletion overall (41% informative cases). 18q/dcc aberrations were associated with the progression of early to late carcinoma, rather than with increasing adenoma size, as has been previously reported. Both p53 alterations and dcc deletions were detected at a higher frequency in distal tumours than in proximal malignancies. Two tumours exhibiting microsatellite instability in both markers were each of proximal origin.

Double-blind, controlled, multicenter study of indobufen versus placebo in patients with intermittent claudication.

The objective of the study was to evaluate the efficacy and safety of indobufen compared with placebo in the treatment of moderately severe intermittent claudication. The study consisted of a four-week single-blind, placebo-controlled run-in phase, followed by a six-month double-blind randomized treatment period. A total of 302 patients were allocated to treatment with either placebo (154 patients) or indobufen (148) 200 mg twice daily. The results of the overall intention-to-treat analysis of the study population showed statistically significant superiority of indobufen over placebo after six months for both the initial (ICD) and absolute claudication distances (ACD). The ICD before treatment with indobufen or placebo averaged 137.9 +/- 68.2 and 136.6 +/- 63.2 m (mean +/- SD), respectively. After six months' treatment with active drug or placebo, this parameter reached 227.9 +/- 174.4 and 153.1 +/- 86.8 m (mean +/- SD), respectively (p < 0.01). Similar results were obtained on ACD. The reduction of lower limb symptoms also suggested a greater clinical benefit in the indobufen-treated patients. There was no significant change in either group in the ankle/arm pressure ratio at the end of treatment. Adverse events of any type were reported by 18 patients (12.2%) in the indobufen group and by 11 patients (7.2%) in the placebo group. The mechanism whereby the drug is effective in this clinical condition could be related to both its antiplatelet and hemorheologic effects.

The use of a latissimus dorsi myocutaneous flap to cover an axillobifemoral vascular prosthetic graft.

We describe a case of seroma formation with skin necrosis overlying an axillobifemoral dacron graft, which was treated by excision of the affected skin and closure using a latissimus dorsi myocutaneous flap.

Distal femoropopliteal bypass using a composite graft of PTFE and non-reversed saphenous vein.

The results of femoropopliteal bypass to the infragenicular popliteal artery, in the absence of suitable saphenous vein have, in the main, been disappointing. We present a new type of composite graft, for use when the distal anastomosis is below the knee, which avoids the potential problems of prosthetic graft alone. The graft consists of a proximal segment of 6 mm expanded PTFE (Gore-Tex; or Impra), anastomosed to transposed non-reversed autologous saphenous vein. Forty-two patients were studied following unilateral, below knee composite femoropopliteal graft surgery for severe claudication or critical ischaemia. Pressure indices were calculated along with intraoperative flow rate, and all patients were followed up at regular intervals to assess graft patency. During the study period three patients died and graft occlusion occurred in a further eight. Analysis of the cumulative patency curve revealed that the majority of occlusions occurred in the first 3 months. The patency at 12 and 18 months was encouraging with values of 84% and 79% respectively. Comparison of pressure indices revealed a significant increase following surgery (P less than 0.001). The postoperative pressure index appeared to predict the grafts likely to occlude and the intraoperative flow rates mirrored a similar trend. Grafts which occluded had a significantly lower pressure index and flow rate (P less than 0.01, P less than 0.002, respectively). Our results suggest that for infragenicular femoropopliteal bypass grafting where full length in-situ vein graft is not possible; a composite graft using PTFE with non-reversed vein is a good alternative.

Benign axillary epithelial lymph node inclusions--a histological pitfall.

We present two cases of axillary epithelial lymph node inclusions in the presence of benign and malignant breast disease. Although the presence of lymph node inclusions is well recognized at other sites in the body, their presence in the axillary nodes of women with breast disease necessitates close attention. This is particularly true in women with malignant breast disease as misinterpretation may lead to inappropriate treatment.

Distal arterial bypass by composite grafting.

The use of non-autogenous prostheses for femorodistal grafting has been attended by relatively poor patency rates. We have attempted to improve on these disappointing results by fashioning a composite graft using expanded PTFE (GORE-TEX) and transposed non-reversed saphenous vein, placed between the femoral artery and anterior tibial artery. We report the early results using this technique in 25 critically ischaemic limbs. At 12 months, the cumulative graft patency for this group of patients was 65 per cent (mean follow-up of 19 months). Eighteen of the twenty-five limbs were saved and there was no mortality. This technique offers a useful alternative to other forms of distal grafting and appears superior to the results obtained using non-autogenous femorodistal conduits.

The measurement of limb blood flow using technetium-labelled red blood cells.

A method for measuring blood flow below the knee during reactive hyperaemia induced by 3 min of arterial occlusion has been developed. Subjects are positioned with lower limbs within the field of view of a gamma camera and pneumatic cuffs are placed below the knees to isolate the blood and induce a hyperaemic response. The remaining blood pool is labelled with 99Tcm-labelled red cells. Blood flows have been derived from the initial gradients of time-activity curves and from equilibrium blood sampling. The technique has been validated using a tissue-equivalent leg phantom and peristaltic pump. The method has been applied to a small group of patients with peripheral vascular disease and to normal controls. The mean value (+/- SD) of limb perfusion for normal controls was found to be 16.4 +/- 3.0 ml/100 ml/min and for patients with intermittent claudication was 5.1 +/- 2.6 ml/100 ml/min. Flow measurements are found to correlate with clinical findings and with symptoms. Reproducibility (established by repeated measurements) is high. The method is well tolerated even by patients suffering from rest pain.

Phase II trial of epirubicin in gastric cancer.

Patients with advanced inoperable or recurrent adenocarcinoma of the stomach received an iv bolus of epirubicin (75 mg/m2) every 3 weeks. Partial responses were observed in four of 24 evaluable patients (17%). Treatment was generally well tolerated; a drop in left ventricular ejection fraction was observed in one patient who had received 450 mg/m2 of epirubicin.