[Laboratory variables and stratification of small-cell lung cancer patients: recommendations for therapeutic trials and for clinical practice guidelines]. / Variables biologiques et stratification des patients porteurs de cancer bronchopulmonaire à petites cellules: recommandations pour les essais cliniques et les guides de bonne pratique.

OBJECTIVE: To identify, through a systematic review of the literature, the laboratory variables that, in addition to performance status and to extent of the disease, would allow a more accurate stratification of small-cell lung cancer patients who participate in chemotherapy trials, with or without radiotherapy. Secondary aim: to compare the results of our systematic review with the recommendations made in current clinical practice guidelines. METHODS: Update of two recently published systematic reviews, without meta-analysis, following the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials statement. RESULTS: Of 1143 publications retrieved, exclusion and inclusion criteria allow us to include 13 studies in our review. The three variables which were the most often found significant in multivariate statistical analysis, were: pre-therapeutic levels of laboratory variables (13/13), performance status (12/13), and degree of tumour invasion (10/10). Among the laboratory variables, serum lactate dehydrogenase (LDH) is the only one that was quite consistently found to be of independent prognostic significance, with p values or hazard ratios quite close to those obtained with performance status, or with extent of the disease. The recommendations made in the four clinical practice guidelines that we retrieved, are often vague regarding laboratory variables, and sometimes they even contradict each others. CONCLUSIONS: Available evidence would support the recommendation that pretreatment LDH should be systematically measured in order to stratify patients in therapeutic trials. If other laboratory variables were to be measured in addition to LDH for this purpose, it seems that alkaline phosphatase (ALP), and to a lesser extent, sodium and white blood cell counts, might be the best suited ones. Nevertheless, further studies are necessary to more clearly support this latter recommendation. Available evidence would not support the measurement of any other laboratory variable in this context, before, during, or after treatment. Our recommendations are more in agreement with the recommendations made in the clinical practice guidelines that use evidence-based methods than with the guidelines that do not.

[Biological variables and stratification of patients with inoperable non-small-cell bronchial cancer: recommendations for future trials]. / Variables biologiques et stratification des patients atteints de cancer bronchique non à petites cellules non opérés: recommandations pour de futurs essais.

OBJECTIVE: To identify, through a review of the literature, the laboratory variables that would allow a more accurate stratification of unresected non small-cell lung cancer patients who participate in clinical trials. METHOD: Systematic review, without meta-analysis, following the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials statement. RESULTS: Of 1106 publications retrieved, we were able to include only fourteen studies in our review. Available evidence would support the use of several laboratory variables as prognostic covariables to stratify non resected non small-cell lung cancer patients in clinical trials, but blood haemoglobin would be the only one that could be recommended on a routine basis, and only in patients treated with radiotherapy (three studies out of three). The possible consequences in terms of therapeutic decision of haemoglobin measurements remain however to be clarified. CONCLUSION: Until better designed studies are published, a number of arguments would support the pre-treatment measurements of the following variables in patients participating in clinical trials: blood haemoglobin, white blood cell count with differential, serum LDH, albumin, calcium, and NSE. Further studies would also be necessary to support the addition to this list, of other tumour markers (including Cyfra 21-1), and/or measurements during or after treatment.

Carcinoembryonic antigen as an independent prognostic factor of recurrence and survival in patients resected for colorectal liver metastases: a systematic review.

PURPOSE: We attempted to answer the question of whether serum levels of carcinoembryonic antigen provide prognostic information, in terms of survival, in patients resected for colorectal liver metastases, independently of that provided by other commonly used radioclinical and pathologic factors. METHOD: We performed a systematic review, without meta-analysis, of the biomedical literature using the methodology recommended by the Committee on Evidence-Based Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine. RESULTS: Despite the absence of sufficient details about the methods used to measure serum carcinoembryonic antigen in the 14 studies reviewed, strong arguments exist to include preoperative carcinoembryonic antigen measurements in future trials on the subject. In particular, preoperative carcinoembryonic antigen was found to be significant in the two studies with the greatest number of patients having a preoperative carcinoembryonic antigen assay, in the four studies with the most recent series of patients, in the study in which preoperative carcinoembryonic antigen was used as a continuous variable, and in the study in which preoperative carcinoembryonic antigen was used in terms of doubling time. Postoperative carcinoembryonic antigen was found to have a prognostic significance in the only two studies that evaluated this variable. CONCLUSION: Taking into account the possible reasons for disagreements regarding carcinoembryonic antigen prognostic value between the 14 studies reviewed, we propose some recommendations to improve the reproducibility and the quality of future studies in this field. In particular, we stress the need for a higher degree of multidisciplinary collaboration in clinical trials.

[Unresected colorectal liver metastases: prognostic value of laboratory variables]. / Métastases hépatiques non opérées des cancers colorectaux: valeur pronostique des variables biologiques.

OBJECTIVE: To search for laboratory variables having independent prognostic signification in patients with unresected colorectal liver metastases. METHODS: We have systematically reviewed the biomedical literature using the methodology recommended by the Committee on Evidence-Based Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials Statement. RESULTS: Of 644 publications retrieved, the application of strict exclusion and inclusion criteria allowed us to include only eight studies in our systematic review. The main laboratory variables evaluated in these eight studies were serum carcino-embryonic antigen, alkaline phosphatase, albumin, bilirubin, and plasma prothrombin time. None of these variables were unanimously found to have an independent prognostic significance. A meta-analysis was not possible, mainly because of heterogeneity within the primary studies and these contradictory results. CONCLUSIONS: Current evidence would not support the routine use of laboratory variables as independent prognostic variables in patients with unresected colorectal liver metastases. Taking into account the inadequate quality of the published studies, this negative conclusion might be provisory only. Until better designed studies are published, a number of arguments would support to recommend pre-treatment measurement of serum carcino-embryonic antigen and alkaline phosphatase in patients participating in clinical trials.

Clonidine premedication decreases propofol consumption during bispectral index (BIS) monitored propofol-ketamine technique for office-based surgery.

BACKGROUND: Propofol-ketamine anesthesia is a room air, spontaneous ventilation (RASV), dissociative intravenous (IV) sedation technique reported to have a near-zero postoperative nausea and vomiting (PONV) rate. Clonidine premedication has been reported to control blood pressure intra- and postoperatively, as well as to reduce the requirements for hypnotic agents. The bispectral index (BIS) monitor is a reproducible, objective, observer independent, quantitative measurement of the hypnotic state. OBJECTIVE: This study was designed to compare the propofol consumption rate during BIS monitored propofol-ketamine anesthesia for office-based, elective female facial rhytidectomy in patients with and without clonidine premedication. METHODS: Six patients receiving clonidine (200 microg oral premedication administered 30-60 minutes prior to induction of anesthesia were compared with a recent, historical control group of six patients who received no premedication. A BIS of 60-70 was chosen as the standard of comparison for light hypnotic state. A dilute propofol solution was used to gradually titrate anesthesia to a BIS of 60-70 prior to the administration of ketamine. RESULTS: A statistically significant reduction in propofol consumption was observed in the clonidine premedicated female elective rhytidectomy patients compared with those not receiving the clonidine. Other than modestly increased requirements for IV fluids, there were no adverse effects observed with clonidine premedication.

Facial laser resurfacing with the propofol-ketamine technique: room air, spontaneous ventilation (RASV) anesthesia.

BACKGROUND: Multiple anesthetic approaches exist for full-face laser resurfacing. The propofol-ketamine technique is reviewed as a reasonable alternative to providing adequate anesthesia for full-face laser resurfacing in the office environment. OBJECTIVE: To report outcomes using propofol-ketamine opioid avoidance, room air, spontaneous ventilation monitored anesthesia care (MAC). METHOD: A retrospective chart review of 95 consenting adult patients receiving propofol-ketamine anesthesia in a private practice, office-based setting. RESULTS: An average of 6 (200 mg) ampules of propofol, including waste, were used per patient. All patients received adequate anesthesia as evidence by a lack of movement during surgery. There were no hallucinations, no postoperative nausea or vomiting (PONV), no cardiovascular instability or seizures (clinical signs of lidocaine toxicity), and no hospital admissions for either PONV or pain. CONCLUSION: The propofol-ketamine technique appears to be an excellent alternative anesthetic approach to EMLA cream, tranquilizer-opioid regimens, or general inhalational anesthesia for facial laser resurfacing.

The effect of a dissociative dose of ketamine on the bispectral index (BIS) during propofol hypnosis.

STUDY OBJECTIVE: To compare the effect of a standardized stimulus during propofol-only hypnosis on the bispectral index (BIS) value with the effect of the injection of local anesthesia for surgery during ketamine plus propofol hypnosis (dissociative monitored anesthesia care). To determine whether ketamine increases the level of propofol hypnosis when used in dissociative doses. DESIGN: Descriptive case study. SETTING: Private practice office plastic surgery suites. PATIENTS: 30 nonpremedicated ASA physical status I and II adult female (23) and male (7) patients scheduled for elective cosmetic surgery. INTERVENTIONS: Hypnosis was induced via slow (60 to 80 drops [gtts]/min), dilute (5 mg/ml) propofol solution. Hypnosis was induced using the BIS monitor as an adjunct to traditional vital signs and verbal contact. Patients were engaged in conversation and note was taken of the BIS value when verbal contact was lost and when BIS appeared to stabilize (BIS1). A standardized stimulus (0.3 ml 1% lidocaine plain via 30-gauge needle) was applied to the area of the supraorbital nerve. Note was taken of the highest BIS value (BIS2) in the patient response. The BIS returned to baseline hypnosis (BIS1) and a 50-mg dissociative dose (independent of body weight) of ketamine was administered. Two minutes were allowed to elapse and then the surgeon was allowed to inject the local anesthesia for the proposed surgery. Note was taken of the BIS value (BIS3) in response to the surgeon's injection. MEASUREMENTS AND MAIN RESULTS: The average delta (BIS2 - BIS1) was 9.5 + 6.9. Patients did not move in response to the surgeon's injection: BIS3 = BIS1. When movement occurred, the injection was terminated and additional ketamine was given before resuming the injection. Sixteen patients received ketamine 50 mg, 12 received ketamine 100 mg, one received ketamine 150 mg, and one received ketamine 200 mg. Men required an average 19% less propofol than women in this group. CONCLUSION: This study demonstrated a positive BIS response to a standardized local anesthetic stimulus during propofol-only hypnosis and a zero response during ketamine plus propofol hypnosis (dissociative anesthesia). Ketamine administered in dissociative doses does not deepen the level of propofol hypnosis. Hypnosis alone does not imply general anesthesia. Patients move in response to inadequate local anesthesia. Because the ketamine analgesia is only transitory and the primary analgesia is not given intravenously, propofol-ketamine technique is not a total intravenous anesthetic technique (TIVA). Instead, propofol-ketamine technique may be classified as a form of monitored anesthesia care (MAC).

Propofol-ketamine technique: dissociative anesthesia for office surgery (a 5-year review of 1264 cases).

Propofol-ketamine technique is a room air, spontaneous ventilation (RASV), intravenous dissociative anesthetic technique which simulates the operating conditions of general anesthesia without the increased equipment requirements or costs. A total of 2059 procedures were performed on 1264 patients by 38 different surgeons. There were no hospital admissions for postoperative nausea and vomiting (PONV) or uncontrolled pain. All patients were pleased with their anesthetic and no hallucinations were reported. Cost:benefit analysis is presented as well as discussion of dissociative anesthesia being exempt from current California law (AB595).

Propofol-ketamine technique.

Case reports are presented demonstrating a new, safe, and simple intravenous technique for outpatient anesthesia. Vinnik's technique requires hypnotic doses of diazepam (Valium) to prevent ketamine-induced hallucinations. The initial hypothesis tested in this clinical series was whether hypnotic doses of propofol would prevent hallucinations from ketamine as satisfactorily as diazepam. Once the initial hypothesis was confirmed, consideration was given to moderating the cost of propofol by determining the effect of two levels of midazolam premedication on propofol requirements. Hypnotic doses of propofol do prevent ketamine-induced hallucinations. It is possible to achieve significant propofol savings by premedication with midazolam without compromising patient readiness for discharge by the end of the first postoperative hour.

Embryotoxicity and teratogenicity of formocresol on developing chick embryos.

White Leghorn chick embryos were used to investigate the embryotoxicity and teratogenicity of 25 and 50% Buckley's formocresol. Embryos were injected at 48 h and sacrificed on the ninth day of incubation. The percentage of mortality of sham and vehicle controls was 4.8 and 17.7%, respectively, whereas eggs injected with 25 and 50% formocresol displayed a 40 and 100% mortality rate. Gross morphological abnormalities, weights, and crown-rump lengths were determined, demonstrating that Buckley's formocresol is embryotoxic and teratogenic in chick embryos. Gross morphological changes were noted to include cranial hematomas, facial abnormalities, eye and beak deformities as well as alterations in feather germ appearance. Histological changes included alterations in the organization of the eyes, and formation of the beak, palate, vasculature, musculature, cartilage, and bone. Moreover, experimental embryos displayed a retardation of development in that they lagged behind their controls by approximately 24 to 36 h.