Antibiotic exposure and the risk of colorectal adenoma and carcinoma: a systematic review and meta-analysis of observational studies.

AIM: The Incidence of colorectal cancer (CRC) is increasing, and evidence suggests that maladaptation of the bowel microbiome may be associated with colorectal carcinogenesis. Consumption of antibiotics may cause imbalance of the bowel microbiome but research assessing an association between antibiotic exposure and CRC is inconsistent. The aim of this systematic review and meta-analysis was to appraise and synthesize the available evidence. METHOD: The MEDLINE, EMBASE and CINAHL databases were searched for published observational studies. We included eight studies of 3 408 312 patients. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the odds of CRC following antibiotic exposure were estimated. Sensitivity analyses were performed according to exposure definition, study design and risk of bias. RESULTS: A weak association between antibiotic exposure and CRC was demonstrated when exposure was assessed cumulatively by the number of prescriptions (OR 1.204, 95% CI 1.097-1.322, P < 0.001) or duration of antibiotic exposure (OR 1.168, 95% CI 1.087-1.256, P < 0.001). Antibiotic exposure assessed as a binary variable demonstrated no association with CRC. CONCLUSION: The findings suggest a weak association between cumulative antibiotic consumption and risk of CRC but no causal conclusions can be made. Limitations include the heterogeneity and quality of the available research, particularly with regard to measurement of antibiotic exposure.

Laparoscopic pyeloplasty: the retroperitoneal approach is suitable for establishing a de novo practice.

BACKGROUND: Laparoscopic dismembered pyeloplasty has become the "gold-standard" procedure for pelviureteric junction (PUJ) obstruction but consists of a steep learning curve especially via the retroperitoneal route. AIMS: To examine the feasibility and safety of introducing this technique via the retroperitoneal approach to a laparoscopic naïve center. SETTINGS AND DESIGN: A retrospective data analysis of a single surgeon's (NEO) series from a large UK teaching hospital. MATERIALS AND METHODS: The notes and imaging of all patients who underwent pyeloplasty for PUJ obstruction by NEO during a five-year period were reviewed. STATISTICAL ANALYSIS: Parametric and nonparametric data are presented analyzed with Excel XP (Microsoft, Redmond, WA, USA). RESULTS: Our series consists of 67 patients. Three ports were used in 47/57 (82%), and the antegrade technique for stent insertion was utilized in 41/67 (61%). Median time to drink, eat, and mobilize was one day (range one to two), and to discharge three days (range three to four). Two patients required conversion to an open procedure, and two developed intraoperative complications. Postoperative complications at 30 (three major, seven minor) and 90 days (three major, three minor) are presented. With median follow-up of 15 months 61/65 (94%) patients were unobstructed, and 57/63 (90%) of patients were pain-free. Two patients re-obstructed requiring further surgery. CONCLUSIONS: Analysis of our series of patients illustrates that adopting a policy of retroperitoneal laparoscopic pyeloplasty for primary PUJ obstruction is feasible without compromising patient safety or functional results. There is no need to breach the peritoneum to facilitate the learning curve.

The laparoscopic nephrectomy learning curve: a single centre's development of a de novo practice.

OBJECTIVE: There has been a dramatic increase in the interest and practice of laparoscopic urology, with nephrectomy having become the commonest laparoscopic urological procedure. Compared with open nephrectomy, it results in reduced morbidity and shorter convalescence times while maintaining oncological safety. However, while these results predominately stem from institutions with well developed laparoscopic programmes, little is known about the results in centres that have newly adopted this technique. The introduction of a laparoscopic urological service at the Royal Hallamshire Hospital provided an opportunity to study these factors. METHODS: Since the appointment in October 2000 of a urological surgeon (N Oakley) to develop the laparoscopic service, there have been over 200 laparoscopic procedures including 121 nephrectomies performed at this centre. Full details were collected for each of these cases, and in addition, compared with retrospective data for 50 open nephrectomies performed during the same time period. RESULTS: With increased operator experience the median operative duration, complication, transfusion, and conversion rates significantly improved. While a learning curve was evident, the overall operative complication (9%) and conversion rates (6%) were low, in addition to patient morbidity (16.5%) and mortality (0%) rates, showing that this learning curve had no deleterious effects upon patient care. The median hospital stay was four days, which reduced to three with experience and was significantly shorter than for open nephrectomy at this institution (p = 0.001). CONCLUSIONS: The development of a successful laparoscopic programme can be achieved with a comparatively short learning curve and without detriment to the patient provided the necessary steps are observed.

Day-case ureteroscopy: an observational study.

OBJECTIVE: To evaluate the outcome after day-case ureteroscopy (used in diagnosing and managing ureteric disease, primarily urolithiasis), as awareness of reduced resources has resulted in increasing pressure to undertake procedures in a day-surgery setting. PATIENTS AND METHODS: All patients presenting to the unit and requiring ureteroscopy between May 1995 and May 2000 were considered for a day-surgery procedure. The assessment of suitability comprised anaesthetic and social factors; no urological criteria precluded a day-surgery procedure. Outcomes after day-case ureteroscopy, including immediate or delayed admissions and subsequent inpatient management, were reviewed retrospectively. RESULTS: Sixty-three day-case ureteroscopies were performed on 56 patients (mean age 47 years, range 19-78); eight procedures were diagnostic. Therapeutic ureteroscopies included one balloon dilatation of a ureteric stricture and 54 procedures for urolithiasis, with 98% stone clearance. Most patients were discharged with a JJ stent in situ. Of nine patients requiring immediate admission, seven were for pain control; eight were discharged on the following day. Seven patients required delayed admission 1-13 days after the procedure, three for stent-related symptoms and three for infection. No significant predictors of immediate or delayed admission were identified, although antibiotic prophylaxis was associated with a reduced admission rate. CONCLUSION: Ureteroscopy can be used successfully as a planned day-case procedure in a dedicated day-surgery unit, with few patients requiring hospitalization. Implementation of analgesia protocols and routine antibiotic prophylaxis may reduce admission after day-case ureteroscopy.

Endobrst: simple and safe is best.

Minimal-access treatment for ureteropelvic junction (UPJ) obstruction is becoming increasingly complex. Is there still a place for the simple procedure of balloon dilatation? To examine the symptomatic and renographic results of patients at least 6 months after balloon disruption of an obstructed UPJ, we carried out a prospective audit of outcome as judged by DTPA renograms and clinical follow-up. The procedure has been performed on a total of 21 renal units (20 patients) with follow-up of 6 to 30 months (mean 22 months). Of these, 18 (86%) were asymptomatic at 3 months, although this success rate dropped to 17 (81%) by 6 months. Renographic split function improved in 11 renal units, and excretion improve in 14. Perioperative complications were few and associated with stent insertion. Three of the patients in whom the procedure failed went on to nephrectomy (14%); all had poor renal function (split <20%) at presentation. Although the quoted success rates are lower for endoluminal balloon rupture of stenosis treatment than open pyeloplasty, the former technique has significantly less morbidity. Our nephrectomy rate reflects our less than ideal early patient selection, and our balloon dilation technique is not recommended as a salvage procedure for patients in whom nephrectomy is inevitable. The learning curve is quick to climb, and this is a fundamentally simple procedure with medium-term results that remain encouraging.

Clinical implications of prostate-specific antigen (PSA).

Prostate-specific antigen(PSA) is currently the tumour marker of choice for prostatic carcinoma. This article examines the current literature on the application of PSA for cancer detection (concentrating on values of PSA in the normal and 'grey' areas of 2.5-10 ng/ml), in staging of the disease and prediction of treatment response. These areas in particular have been refined by the use of PSA indices (PSA density, velocity, age ranges) and the article focuses on the recent studies analysing their standing in clinical practice.

A microdialysis study on pineal melatonin rhythms in rats after an 8-h phase advance: new characteristics of the underlying pacemaker.

This study describes the use of the microdialysis technique to elucidate specific properties of the circadian pacemaking system in the hypothalamus, by measurement of melatonin production in the pineal gland. Melatonin has appeared to be a reliable marker of the pacemaker activity, which is influenced by the light/dark cycle. A phase shift in the light/dark cycle was applied to perturb the rhythm generating system. An 8-h phase advance resulted in the disappearance of melatonin production over two days, with basal levels comparable to normal daytime levels. In the subsequent return of rhythmic melatonin production, new clock characteristics could be revealed, due to the high time-resolution measurements of microdialysis. While half of the animals still did not show any rhythmicity, the other half of the animals regained rhythmicity with entrained onset of melatonin production, while the offset was variable and not stably entrained to lights on. Ten days after the shift, the system had completely recovered and all animals regained normal rhythmicity, in phase with the new light/dark cycle. The results are interpreted in terms of the two-oscillator model, with one oscillator reacting with a phase advance and the other with a phase delay to adapt to the phase shift.

Development of tolerance in mice to the sedative effects of the neuroactive steroid minaxolone following chronic exposure.

Minaxolone is a potent ligand for the neurosteroid binding site of the GABAA, receptor. In radioligand binding studies to rat brain membranes, minaxolone caused a 69% increase in [3H]muscimol binding and a 25% increase in [3H]flunitrazepam binding and inhibited the binding of [3H]TBOB with an IC50 of 1 microM. In mice, minaxolone (100 mg/kg, orally) had marked sedative effects as indicated by a reduction in locomotor activity. Chronic dosing with minaxolone (100 mg/kg, orally, once daily for 7 days) resulted in a loss of sedative response to an acute dose of the drug, indicating development of tolerance. Chronic dosing with temazepam (10 mg/kg, orally, once daily for 7 days) resulted in the development of tolerance to an acute dose of temazepam; however, the two drugs did not appear to be cross-tolerant, indicating that they may have a different mechanism of action at the level of the GABAA receptor.

The role of the radiologist in surgical management: an audit of clinico-radiological conferences.

A prospective analysis of the radiological findings and final diagnoses of 342 patients discussed at joint surgical/radiological conferences over a seven-month period was undertaken in an attempt to define the role of the radiologist in the clinical management of surgical patients. Although the diagnosis had already been correctly made on clinical or radiological grounds in 38% (130/342) of patients presented at the X-ray conferences, careful review of the films resulted in an immediate firm diagnosis in a further 9% (31/342), or promoted further radiological investigations which were responsible for an eventual definitive diagnosis in 20% of the remainder (32/169). The input of the radiologist in selecting the most appropriate additional investigation was particularly valuable in the management of more complex clinical problems.

Randomized comparison of oral and intravenous fluid regimens after gallbladder surgery.

Numerous studies of post-operative fluid status have utilized sophisticated measurements of electrolyte distribution and fluid shift without relating results to clinical practice. The aim of this prospective randomized study was to investigate the response of patients undergoing abdominal surgery of moderate severity to conservative post-operative fluid administration. Forty-five patients undergoing open cholecystectomy were randomized to receive 2.51 of fluid (1 l normal saline and 1.51 5% dextrose), 1 l of normal saline, or free oral fluids (groups 1, 2, 3, respectively). Serum and urine osmolality and electrolytes were measured pre-operatively and at 24 and 48 h post-operatively. Patients remained in the study irrespective of the urine output. Plasma electrolytes and osmolality remained within normal limits in all three groups despite significant changes in urine electrolyte and osmolality in groups 2 and 3. This confirms that a conservative approach to fluid administration has no detrimental effect on hydration in fit patients with uncomplicated surgery.

A prospective audit of simple mastectomy under local anaesthesia.

The treatment options for breast cancer in elderly or unfit patients can be complicated by their coexistent medical problems. This study assesses the feasibility of simple mastectomy under local anaesthesia by means of a prospective audit on 36 patients with breast carcinoma and an ASA grade of 3 or worse. In 27 patients the tumour had escaped from tamoxifen control, no patients having had previous radiotherapy. Operation time ranged from 40 to 70 min, average blood loss was 200 ml and an average inpatient stay of 5 days. Only two patients had a resection margin less than 1 cm and in none was there significant morbidity or mortality despite the patients' poor pre-operative medical condition. This confirms the potential of using local anaesthetic for simple mastectomy. Eliminating the morbidity/mortality due to general anaesthesia widens the range of treatment available (especially to medically unfit patients) giving them the option of a rapid resolution to what could be a distressing protracted condition.

Local anaesthesia for major general surgical procedures. A review of 116 cases over 12 years.

Between 1980 and 1992, 116 patients had either a simple mastectomy (32) or intra-abdominal procedures (84) under local anaesthesia (0.5-1% lignocaine with 1:200 000 adrenaline). A wide variety of general surgical procedures were feasible using only supplementary intravenous sedation (54%). Complications were uncommon and related to surgical procedure (three incorrect diagnoses, three procedures impossible) rather than the anaesthetic technique. There were no anaesthetic toxicity or postoperative problems. Local anaesthesia is extremely safe and facilitates larger surgical procedures than is generally appreciated.

Exogenous melatonin entrains rhythm and reduces amplitude of endogenous melatonin: an in vivo microdialysis study.

The circadian rhythm of melatonin production was studied using on-line, in vivo microdialysis in the rat pineal gland. With this technique it was possible to record a pronounced melatonin rhythm with very high time resolution. Three phase-markers of the rhythm were calculated from the data, indicating increase (IT50), decrease (DT50) and amplitude of the rhythm. Comparing these phase markers led to several conclusions. Entrainment of the rhythm under constant darkness was performed with melatonin administration at different circadian stages [circadian time (CT) 8 and CT12] and for different periods of time (2 weeks and 4 weeks). Also, entrainment was established by applying 15 min light pulses at CT0. Entrainment of IT50 with melatonin partially uncoupled it from DT50. Four weeks entrainment in constant darkness (DD) caused a phase-delay in DT50 of 2.2 hr. Entrainment of IT50 with light at CT0 for 2 weeks in DD caused a phase-advance in DT50 of 1.3 hr. The entrainment with melatonin was restricted to a narrow window for melatonin to be applied, since injections at CT8 did not result in entrainment. Exogenous melatonin reduced the amplitude of the rhythm of endogenous melatonin. This effect was not circadian time dependent, since administration at CT8 for 2 weeks and at CT12 for 4 weeks resulted in a highly significant decrease. Light did not seem to have an effect on the amplitude. The data presented here provide us with new information about the nature of entrainment by melatonin. Since the present development of melatonergic agents for clinical use focuses on the entrainment capacity, effects of these compounds on amplitude of circadian rhythms needs to be addressed. In vivo microdialysis seems to be a good technique for that.

What should I do about my patient's gall stones?

The problem of benign biliary disease is one that causes significant morbidity and social economic strain in the western world. The classical treatment, cholecystectomy, has been challenged by various medical and surgical techniques in a seemingly random nature. The development of the treatment of gall stone disease is reviewed by analysis of published studies over the last 20 years. The advantages and disadvantages are discussed as an overview and summary of the current management of gall stone disease in the light of our knowledge of its malignant potential.