Recommendations for the use of next-generation sequencing in patients with metastatic cancer in the Asia-Pacific region: a report from the APODDC working group.

INTRODUCTION: Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS: The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS: The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION: This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.

Monte Carlo simulation and linear stability analysis of Turing pattern formation in reaction-subdiffusion systems.

Subdiffusion is an important physical phenomenon observed in many systems. However, numerical techniques to study it, especially when coupled to reactions, are lacking. In this paper, we develop an efficient Monte Carlo algorithm based on the Gillespie algorithm and the continuous-time random walk to simulate reaction-subdiffusion systems. Using this algorithm, we investigate Turing pattern formation in the Schnakenberg model with subdiffusion. First, we show that, as the system becomes more subdiffusive, the homogeneous state becomes more difficult to destablize and Turing patterns form less easily. Second, we show that, as the number of particles in the system decreases, the magnitude of fluctuations increases and again the Turing patterns form less easily. Third, we show that, as the system becomes more subdiffusive, the ratio between the two diffusive constants must be higher in order to observe Turing patterns. Finally, we also carry out linear stability analysis to validate the results obtained from our algorithm.

Analgesic efficacy of pre-operative etoricoxib for termination of pregnancy in an ambulatory centre.

INTRODUCTION: Etoricoxib is a second generation cyclooxygenase-2 inhibitor with a rapid-onset time and a long duration of action. It is ideal for providing pre-emptive analgesia for ambulatory surgeries. We hypothesised that pre-operative etoricoxib can decrease the use of fentanyl post-operatively, when compared with placebo in patients undergoing termination of pregnancy. We also compared their pain scores, time to discharge, side effects and satisfaction with analgesia post-operatively. METHODS: After approval by the hospital research ethics committee and receipt of informed written consent, we recruited 40 American Society of Anesthesiologists Physical Status Classification I and II patients scheduled for elective first trimester termination of pregnancy. Patients were randomly allocated to receive either oral etoricoxib 120 mg (Group E, n=20) or placebo tablet (Group P, n=20) pre-operatively. A blinded observer evaluated the post-operative pain scores, need for supplementary analgesia, side effects and satisfaction scores. Sample size was calculated (power of 0.8 and alpha=0.05) to detect a 20 percent difference in fentanyl usage. Amount of fentanyl used, pain scores and satisfaction scores were analysed using non-parametric tests. The incidence of side effects was analysed using chi-squared test. RESULTS: Etoricoxib 120 mg significantly decreased the amount of fentanyl required after termination of pregnancy compared to placebo (0 microg/patient, interquartile range [IQR] 0-25 versus 50 microg/patient, IQR 0-50, p-value is less than 0.05). Patients who received etoricoxib 120 mg also had significantly lower pain scores than the placebo group at time of discharge (8 +/- 11 versus 1 +/- 3, p-value is less than 0.05) and at six hours post operation (8 +/- 12 versus 0 +/- 0, p-value is less than 0.01). There was no difference in their side effects, and time to discharge and overall satisfaction were similar in both groups. CONCLUSION: Pre-operative administration of oral etoricoxib 120 mg decreased the use of fentanyl and pain scores after minor gynaecological surgery without significant side effects.

Multimodal antiemetic therapy and emetic risk profiling.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is a common problem with no simple solution. This review highlights factors that are known to increase the risk of PONV. It examines the various data on pharmacological and non-pharmacological methods that have been used to prevent PONV. METHODS: Peer-reviewed journals on the subject were covered. CONCLUSION: Patient, surgical and anaesthetic factors increase the risk of PONV. While patient and surgical factors are understandably difficult to control, a multimodal approach involving both pharmacological and non-pharmacological interventions has been successfully adopted to reduce the incidence of PONV. Various factors have been identified to categorise patients into different profiles to determine their risk of PONV. Perioperative strategies can then be targeted at these patient groups.

Treatment of cerebral palsy with botulinum toxin: evaluation with gross motor function measure.

The objective of this study was to investigate the effects of botulinum toxin A (BTA) injection in reducing muscular spasticity and improving locomotor function in children with cerebral palsy. Thirty-eight children with spastic cerebral palsy who were undergoing regular physical therapy were enrolled. Twenty-eight of these received BTA injection at the hip adductors and/or gastrocnemius, while the other 10, whose parents refused the BTA treatment protocol, served as the comparison group. The main outcome measures were: improvements in the severity of spasticity, walking distance, gross motor function (as assessed with the Gross Motor Function Measure, GMFM), and gait pattern (as assessed with the Physician Rating Scale, PRS), all measured 6 and 12 weeks after the start of BTA treatment. The severity of spasticity and walking distance at baseline did not differ significantly between the two groups. However, the severity of spasticity improved markedly in the BTA group, from 2.7 to 1.5 (Modified Ashworth Scale) at the hip adductor, and from 2.9 to 1.9 at the gastrocnemius at the 6-week follow-up. The walking distance improved from 46.17 m to 55.32 m at the 6-week follow-up, and to 66.6 m at the 12-week follow-up in the BTA group. Marked improvements in the quality of several gross motor functions were also noted in the BTA group. The improvements in spasticity, walking distance, and gross motor function were significantly greater in the BTA group than in the comparison group. The improvements in gait pattern did not differ significantly between the BTA and comparison groups. The findings of this study show BTA injection to be an effective treatment for reducing spasticity and improving gross motor function in children with spastic cerebral palsy. GMFM provides objective evidence regarding functional improvement after treatment in this patient population.

An in vitro evaluation of epidural catheters: tensile strength and resistance to kinking.

The tensile strengths of 12 commercially available brands of epidural catheters were assessed using an Instron material testing device. The mean values of the tensile strengths ranged from 1.89 to 3.74 kilogram force. The extent of catheter occlusion due to kinking was also studied using an in vitro apparatus designed to simulate drug delivery at various degrees of flow restriction. It was determined that reinforced catheters were less likely to be occluded secondary to kinking.

Pulse dye densitometry: a novel bedside monitor of circulating blood volume.

INTRODUCTION: Monitoring of circulating blood volume is important in the management of critically ill patients. Current methods of circulating blood volume measurements such as indicator dilution using radioisotopes or Evans blue dye are unsuitable for clinical application as these tests do not allow for frequent repeated measurements to be done. A direct bedside measurement of circulating blood volume using the principle of pulse dye densitometry was recently introduced. This is essentially an indicator dilution technique using indocyanine green combined with the principle of pulse spectrophotometry. METHODS: This paper aims to review this method of circulating blood volume measurement and provide a summary of the published clinical trials that compared its accuracy with the other conventional methods of circulating blood volume measurement, based on a Medline search, spanning the period 1966 to August 2000. RESULTS: Published studies show that pulse dye densitometry gives comparable results when compared to other conventional methods of blood volume measurement. Its ability to measure circulating blood volume accurately and repeatedly, as frequently as every 20 min makes it suitable for clinical application. CONCLUSION: Pulse dye densitometry provides for a rapid, semi-noninvasive and convenient bedside assessment of circulating blood volume that is applicable clinically. Further studies are needed to ascertain the impact of the use of pulse dye densitometry on the mortality and morbidity of the critically ill.

Fibre-optic aided bougie (FAB) for simulated difficult tracheal intubation.

INTRODUCTION: Difficult intubation remains a key problem and the value of the gum elastic bougie as a first approach is well recognised. MATERIALS AND METHODS: A fine fibre-optic endoscope (Rapiscope, Cook Critical Care) was used in 50 patients to verify placement of a custom-designed hollow plastic bougie prior to "rail-roading" a tracheal tube. Following induction and muscle relaxation, direct laryngoscopy was performed after two-minutes of assisted ventilation. The laryngoscope blade was lowered to simulate difficult intubation and the bougie passed behind the epiglottis. The position of the introducer bougie was then checked using the Rapiscope. Following correct bronchoscopic identification of the tracheobronchial anatomy, a tracheal tube was then "rail-roaded" following withdrawal of the scope. RESULTS: All patients were successfully intubated following identification of the bronchial tree by the Rapiscope: three on the second attempt and the rest on the first. Mean (SD, range) time to successful bronchoscopic confirmation of correct placement of the bougie was 38 s (9.1 s, 19 to 60 s). All bronchoscopic assisted intubation were subsequently confirmed by capnography after tracheal tube insertion. Mean (SD, range) time to successful intubation was 106 s (14 s, 52 to 132 s). CONCLUSION: The fibre-optic assisted bougie (FAB) offers a promising technique in patients who may be difficult to intubate but who can be ventilated. Further developments are required to achieve a faster intubation time but oxygenation may be achieved by jetting down the hollow bougie.

Obstetric admissions to the intensive therapy unit of a tertiary care institution.

INTRODUCTION: Between 0.1% and 0.9% of women develop pregnancy complications which require admission to an intensive therapy unit. The aim of this study was to review all obstetric admissions to the intensive therapy unit at the KK Women's and Children's Hospital from 1998 to 1999 with respect to indications for admission, interventions employed and clinical outcome. METHOD: The medical records of all obstetric patients admitted to the intensive therapy unit during the 2-year period were analysed retrospectively. Subjects were included if they were admitted during pregnancy up to 42 days postpartum. RESULTS: There were 31,725 deliveries in our hospital during the study period of which there were 239 admissions to the intensive therapy unit. Of these, 42% were Malays, 41% Chinese, 12% Indians and 5% other races. 65% stayed 1 day, 24% 2 days, 7% 3 days and 4% more than 3 days. The patients' ages ranged from 18 to 44 years. The indications for admission were hypertension (50%), haemorrhage (24%), respiratory insufficiency (10%), neurological problems (11%) and sepsis (3%). Intervention-wise, 43% of patients required vasoactive infusions, 35% had arterial line placement, 22% central venous pressure monitoring, 21% ventilatory support and 2% pulmonary artery catheter placement. The maternal mortality and stillbirth rates were 1.3% and 3.7% of intensive therapy unit admissions, respectively. CONCLUSION: The admission rate to the intensive therapy unit in our institution was 0.73% of all deliveries during the 2-year study period. Hypertensive disease and haemorrhage were the predominant admitting diagnoses.

Electroanalgesia: its role in acute and chronic pain management.

Interest in nonpharmacologic alternatives to conventional analgesic drugs for the management of acute and chronic pain has lead to an evaluation of the use of electroanalgesic therapies.

Analgesic efficacy of continuous delivery of bupivacaine by an elastomeric balloon infusor after abdominal hysterectomy: a prospective randomised controlled trial.

OBJECTIVE: To investigate the analgesic efficacy and morphine-sparing effect of continuous bupivacaine wound infiltration after abdominal hysterectomy. DESIGN: Prospective, randomised controlled trial. SAMPLE: Fifty-two female ASA I or II patients were enrolled with 26 patients in each of the study and control groups. METHODS: The study group received 0.5% bupivacaine infusion into the incisional (Pfannenstiel) wound via an elastomeric infusor at 2 mL/hr for 48 hours postoperatively plus morphine via a patient controlled analgesia (PCA) pump. The control group had only PCA morphine. RESULTS: There were no significant differences in the visual analogue scores (VAS) for pain nor PCA morphine usage for 48 hours postoperatively CONCLUSION: That continuous infusion of the incisional wound with 0.5% bupivacaine did not confer additional analgesia over PCA morphine after abdominal hysterectomy

Postoperative epidural hematoma or cerebrovascular accident? A dilemma in differential diagnosis.

An elderly lady developed an epidural hematoma following combined spinal-epidural anesthesia with a local anesthetic-opioid mixture for a vaginal hysterectomy. This occurred in association with the use of prophylactic subcutaneously administered unfractionated heparin. She had diabetes, hypertension and had previously undergone coronary artery bypass surgery and right carotid endarterectomy. Warfarin and aspirin were discontinued 2 weeks before the surgery. Postoperatively, an atypical presentation of backache, bilateral sensory loss and left lower limb monoplegia ensued. The initial clinical impression was of a cerebrovascular accident. Magnetic resonance imaging, however, revealed an extensive epidural hematoma that necessitated decompression laminectomy. Progression to paraparesis occurred but the patient gradually regained much of her functionality over the next 2 years.

Combination of intrathecal sufentanil 10 mug plus bupivacaine 2.5 mg for labor analgesia: is half the dose enough?

UNLABELLED: This controlled, double-blinded, prospective trial of 42 parturients in early labor was conducted to determine whether halving the total amount of intrathecal (i.t.) sufentanil and bupivacaine reduced the incidence of systemic hypotension while providing adequate analgesia with minimal lower limb motor block. Combined spinal-epidural analgesia (CSE) was instituted; Group A (n = 21) received a total of 10 microg of sulfentanil plus 2.5 mg of bupivacaine, whereas Group B (n = 21) received half that dose. Compared with Group B, Group A had a higher incidence of hypotension (nine parturients in Group A, two in Group B; P < 0.05), a greater degree of motor block (P < 0.05), and a higher incidence of sedation (nine parturients in Group A were sedated, one in Group B; P < 0.01). Group B had higher pain scores for the first 5 min (P < 0.05) and a lower level of sensory blockade (median of T7 in Group B compared with T4 in Group A; P < 0.01). We conclude that halving the total amount of i.t. 10 microg of sufentanil plus 2.5 mg of bupivacaine is a suitable option for CSE in labor because it reduces the incidence of some side effects, such as hypotension and maternal sedation, without compromising overall high maternal satisfaction. IMPLICATIONS: We showed that adequate labor pain relief could be provided by halving the recommended dose of 10 microg of intrathecal sufentanil plus 2.5 mg of bupivacaine. The larger dose, however, produced faster pain relief, which lasted longer than the reduced dose. The mother and baby were not adversely affected with either dose.

[Median nerve lesions at wrist in cyclists].

The purpose of this study is to detect the median nerve lesions at wrist in professional cyclists. Totally 14 national representative cyclists were included. Each subject was questionnaired and asked to draw their site of hand discomfort, followed by hand grip power test with grasp, lateral pinch and palmar pinch. A control group of 30 medical students were also tested for grip power. Electrodiagnostic examination of bilateral median nerves was then done on every cyclist, including motor and sensory nerve conduction studies, and needle EMG on abductor pollicis brevis and other associated muscles. Of the 28 hands in 14 cyclists, 7 in 4 subjects had neurologic symptoms related to median nerve, and 5 in 4 subjects had abnormal electrodiagnostic examinations. The grip power was significantly better in cyclists than in control. The prevalence of median nerve lesions at wrist in cyclists, although usually mild, was substantially higher than expected. Electrodiagnosis can be used as a sensitive detector for neuropathy even at subclinical stage. It is suggested that cyclists and trainers should be aware of the median nerve lesion during cycling and training in order to take early preventive, diagnostic and therapeutic procedures.

The use of esmolol as an alternative to remifentanil during desflurane anesthesia for fast-track outpatient gynecologic laparoscopic surgery.

We compared esmolol and remifentanil infusions with respect to their effect on intraoperative hemodynamic stability and early recovery after outpatient laparoscopic surgery when administered as IV adjuvants during desflurane anesthesia. After premedication with midazolam 2 mg IV, anesthesia was induced with propofol 2 mg. kg(-1) IV in combination with either esmolol 1 mg. kg(-1) IV (n = 27) or remifentanil 1 microg. kg(-1) IV (n = 26) and succinylcholine 1 mg. kg(-1) IV according to a randomized, double-blinded protocol. Anesthesia was initially maintained with desflurane 2.5% (subsequently titrated to maintain an electroencephalogram-bispectral index value of 60) and nitrous oxide 65% in oxygen. Before skin incision, an infusion of either esmolol (5 microg. kg(-1). min(-1)) or remifentanil (0.05 microg. kg(-1). min(-1)) was started and titrated to maintain the heart rate within 25% of the baseline value. Mivacurium, 0.04 mg/kg IV, bolus doses were administered to maintain a stable peak inspiratory pressure. Esmolol (12.8 +/- 13.1 microg. kg(-1). min(-1)) and remifentanil (0.04 +/- 0.02 microg. kg(-1). min(-1)) infusions were equally effective in maintaining a stable heart rate during these laparoscopic procedures. Although the mivacurium requirement was larger in the Esmolol group (7 +/- 5 vs 3 +/- 4 mg), the Esmolol group reported a smaller incidence of postoperative nausea and vomiting (4% vs 35%). Both drugs were associated with frequent "postanesthesia care unit bypass" rates (78-81%), short times to "home readiness" (119-120 min), excellent patient satisfaction (81-85%), and rapid resumption of normal activities (2.6-3.2 d). Fast-tracked patients were ready for discharge home significantly earlier (112 +/- 46 vs 151 +/- 50 min). We concluded that esmolol infusion is an acceptable alternative to remifentanil infusion for maintaining hemodynamic stability during desflurane-based fast-track anesthesia for outpatient gynecologic laparoscopic surgery.

Brca1 controls homology-directed DNA repair.

Germline mutations in BRCA1 confer a high risk of breast and ovarian tumors. The role of BRCA1 in tumor suppression is not yet understood, but both transcription and repair functions have been ascribed. Evidence that BRCA1 is involved in DNA repair stems from its association with RAD51, a homolog of the yeast protein involved in the repair of DNA double-strand breaks (DSBs) by homologous recombination. We report here that Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DSBs by homologous recombination. The relative frequencies of homologous and nonhomologous DNA integration and DSB repair were also altered. The results demonstrate a caretaker role for BRCA1 in preserving genomic integrity by promoting homologous recombination and limiting mutagenic nonhomologous repair processes.

DNA analysis and persistent hypercalcitoninemia in medullary thyroid carcinoma.

The clinical data of 20 patients with medullary thyroid carcinoma (MTC) treated in Veterans General Hospital (VGH)-Taipei from 1970 to 1991 were reviewed. DNA content of the MTC and postoperative serum calcitonin (CT) were compared to evaluate patients' survival. All three patients with stage IV disease had aneuploid DNA and died within 7 months. The average survival was 4 months. The other 17 patients were all alive at the time of study and the mean follow up was 86 months. Three (3/7) patients had less than total thyroidectomy while only 2 (2/13) of the total thyoidectomized patients needed reoperation because of tumor recurrence. Of the 15 patients with available calcitonin data 11 had persistent post-operative hypercalcitoninemia. Among these 11 patients 5 out of the 6 patients with demonstrable lesions received reoperation; the other five (5/11) without demonstrable lesions were not operated and lived well in spite of persistent hypercalcitoninemia. One in 4 diploid patients and 9 in 12 aneuploid patients had metastatic lesions. No statistical significant correlation was found between the DNA content and survival, metastases or hypercalcitoninemia, although aneuploid MTC tended to be more advanced. We therefore concluded that total thyroidectomy is the treatment of choice for MTC. Persistent postoperative hypercalcitoninemia without clinical demonstrable lesions can be treated conservatively and DNA aneuploidy cannot be used as a reliable indicator of the grade of malignancy for MTC.

Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia.

BACKGROUND: The use of volatile anesthetics for maintenance of anesthesia can enhance the action of non-depolarizing muscle relaxants and interfere with the reversal of neuromuscular blockade. In this study, we studied the antagonism of rocuronium with edrophonium-atropine during propofol- versus sevoflurane-based anesthesia. METHODS: Following induction of anesthesia with propofol (2-2.5 mg kg(-1), i.v.) and fentanyl (1-2 microg kg(-1) i.v.), rocuronium 0.6 mg kg(-1) i.v. was administered to facilitate tracheal intubation. Patients were then randomized to receive either a propofol infusion (100 microg kg(-1) min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular blockade was monitored using electromyography at the wrist, and reversed with edrophonium 1.0 mg kg(-1) and atropine 0.015 mg kg(-1) when the first twitch hight (T1) of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. Anesthetic maintenance with propofol or sevoflurane was continued following reversal until a TOF ratio of 0.7 was attained. RESULTS: The clinical duration of action (i.e., time to 25% T1 recovery) was similar during both propofol- (39.3+/-14.6 min) and sevoflurane-based (48.1+/-19.7 min) anesthesia. However, the reversal time from 25% T1 to TOF ratio of 0.7 was significantly longer with sevoflurane [Median 2.8 (range 0.5-18.8) min] compared with propofol [1.5 (0.75-3) min] (P<0.05). CONCLUSIONS: We conclude that the clinical duration of action after a single dose of rocuronium, 0.6 mg kg(-1) i.v., was similar during both propofol- and sevoflurane-based anesthesia. However, the reversal of rocuronium-induced residual blockade was slower and more variable in the presence of sevoflurane.

The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery.

UNLABELLED: Nonpharmacologic techniques may be effective in preventing postoperative nausea and vomiting (PONV). This sham-controlled, double-blinded study was designed to examine the antiemetic efficacy of transcutaneous acupoint electrical stimulation (TAES) in a surgical population at high risk of developing PONV. We studied 221 outpatients undergoing laparoscopic cholecystectomy with a standardized general anesthetic technique in this randomized, multicenter trial. In the TAES group, an active ReliefBand(Woodside Biomedical, Inc., Carlsbad, CA) device was placed at the P6 acupoint, whereas in the Sham and Placebo groups, an inactive device was applied at the P6 acupoint and at the dorsal aspect of the wrist, respectively. The ReliefBand was applied after completion of electrocautery and remained in place for 9 h after surgery. The incidence of PONV and need for "rescue" medication were evaluated at predetermined time intervals. TAES was associated with a significantly decreased incidence of moderate-to-severe nausea as denoted on the Functional Living Index-Emesis score for up to 9 h after surgery (5%-11% for the TAES group vs 16%-38% [P < 0.05] and 15%-26% [P < 0.05] for Sham and Placebo groups, respectively). TAES was also associated with a larger proportion of patients free from moderate to severe nausea symptoms (73% vs 41% and 49% for Sham and Placebo groups, respectively; P < 0.05). However, there were no statistically significant differences among the three groups with regard to incidence of vomiting or the need for rescue antiemetic drugs. We conclude that TAES with the ReliefBand at the P6 acupoint reduces nausea, but not vomiting, after laparoscopic cholecystectomy. IMPLICATIONS: Transcutaneous acupoint electrical stimulation at the P6 acupoint reduced postoperative nausea, but not vomiting, in outpatients undergoing laparoscopic cholecystectomy procedures.

Comparison of the costs and recovery profiles of three anesthetic techniques for ambulatory anorectal surgery.

BACKGROUND: Given the current practice environment, it is important to determine the anesthetic technique with the highest patient acceptance and lowest associated costs. The authors compared three commonly used anesthetic techniques for anorectal procedures in the ambulatory setting. METHODS: Ninety-three consenting adult outpatients undergoing anorectal surgery were randomly assigned to one of three anesthetic treatment groups: group 1 received local infiltration with a 30-ml mixture containing 15 ml lidocaine, 2%, and 15 ml bupivacaine, 0.5%, with epinephrine (1:200,000) in combination with intravenous sedation using a propofol infusion, 25-100 microg. kg-1. min-1; group 2 received a spinal subarachnoid block with a combination of 30 mg lidocaine and 20 microg fentanyl with midazolam, 1-2-mg intravenous bolus doses; and group 3 received general anesthesia with 2.5 mg/kg propofol administered intravenously and 0.5-2% sevoflurane in combination with 65% nitrous oxide. In groups 2 and 3, the surgeon also administered 10 ml of the previously described local anesthetic mixture at the surgical site before the skin incision. RESULTS: The mean costs were significantly decreased in group 1 ($69 +/- 20 compared with $104 +/- 18 and $145 +/- 25 in groups 2 and 3, respectively) because both intraoperative and recovery costs were lowest (P < 0.05). Although the surgical time did not differ among the three groups, the anesthesia time and times to oral intake and home-readiness were significantly shorter in group 1 (vs. groups 2 and 3). There was no significant difference among the three groups with respect to the postoperative side effects or unanticipated hospitalizations. However, the need for pain medication was less in groups 1 and 2 (19% and 19% vs. 45% for group 3; P < 0.05). Patients in group 1 had no complaints of nausea (vs. 3% and 26% in groups 2 and 3, respectively). More patients in group 1 (68%) were highly satisfied with the care they received than in groups 2 (58%) and 3 (39%). CONCLUSIONS: The use of local anesthesia with sedation is the most cost-effective technique for anorectal surgery in the ambulatory setting.