Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific. Presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, March 11, Miami, Florida.     

Déficit émotionnel et intelligence machiavélique : étude des interrelations entre l'échelle d'alexithymie de Toronto (TAS-20) et l'inventaire mach-iv dans une population de 201 étudiants

The aim of the study was to explore the relationship between alexithymia and machiavellianism in a group of 201 university students. The subjects filled out the TAS-20 and the MACH-IV forms. The results showed firstly, a significant correlation between the two total scores (r = 0.35, P < 0.05), and secondly between the identification of feelings subscale of the TAS-20 and the opinions about human nature subscale of the Mach-IV (r = 0.44, P < 0.05). The results were discussed in light of the different factors (depression, dependency, psychoticism…) that could explain the relationship between the two concepts.     

Cryosurgical treatment of gingival melanin pigmentation with tetrafluoroethane.

OBJECTIVE: To introduce 1,1,1,2 tetrafluoroethane (TFE), as a new material for cryosurgery of gingival melanin pigmentation (GMP). STUDY DESIGN: Twenty-one patients with GMP were treated using a TFE-cooled cotton swab. Standard digital images of pigmented areas were measured preoperatively and postoperatively with image-analyzing software. The Mann-Whitney U test was used for statistical analysis. RESULTS: Keratinization was completed 3 to 4 weeks after application, without any trace of pigmentation. Statistical analysis revealed a significant difference between preoperative and postoperative measurements of pigmented areas (P < .05). During the follow-up period, no side effects were observed and improved esthetics were maintained up to month 30. CONCLUSIONS: The clinical outcomes of cryosurgery with TFE for treatment of GMP are very satisfactory. The use of TFE for cryosurgical treatment of GMP is practical and inexpensive. Moreover, unlike other cryosurgery methods no special equipment is required, and it is safe to store in the dental clinic.     

Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep

Background: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated.

Methods: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg [middle dot] kg-1 [middle dot] h-1) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat.

Results: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1).     

Response of lumbar paraspinal muscles spindles is greater to spinal manipulative loading compared with slower loading under length control.

BACKGROUND CONTEXT: Spinal manipulation (SM) is a form of manual therapy used clinically to treat patients with low back and neck pain. The most common form of this maneuver is characterized as a high-velocity (duration <150 ms), low-amplitude (segmental translation <2 mm, rotation <4 degrees , and applied force 220-889 N) impulse thrust (high-velocity, low-amplitude spinal manipulation [HVLA-SM]). Clinical skill in applying an HVLA-SM lies in the practitioner's ability to control the duration and magnitude of the load (ie, the rate of loading), the direction in which the load is applied, and the contact point at which the load is applied. Control over its mechanical delivery is presumably related to its clinical effects. Biomechanical changes evoked by an HVLA-SM are thought to have physiological consequences caused, at least in part, by changes in sensory signaling from paraspinal tissues. PURPOSE: If activation of afferent pathways does contribute to the effects of an HVLA-SM, it seems reasonable to anticipate that neural discharge might increase or decrease in a nonlinear fashion as the thrust duration approaches a threshold value. We hypothesized that the relationship between the duration of an impulsive thrust to a vertebra and paraspinal muscle spindle discharge would be nonlinear with an inflection near the duration of an HVLA-SM delivered clinically (<150 ms). In addition, we anticipated that muscle spindle discharge would be more sensitive to larger amplitude thrusts. STUDY DESIGN/SETTING: A neurophysiological study of spinal manipulation using the lumbar spine of a feline model. METHODS: Impulse thrusts (duration: 12.5, 25, 50, 100, 200, and 400 ms; amplitude 1 or 2 mm posterior to anterior) were applied to the spinous process of the L6 vertebra of deeply anesthetized cats while recording single unit activity from dorsal root filaments of muscle spindle afferents innervating the lumbar paraspinal muscles. A feedback motor was used in displacement control mode to deliver the impulse thrusts. The motor's drive arm was securely attached to the L6 spinous process via a forceps. RESULTS: As thrust duration became shorter, the discharge of the lumbar paraspinal muscle spindles increased in a curvilinear fashion. A concave-up inflection occurred near the 100-ms duration eliciting both a higher frequency discharge compared with the longer durations and a substantially faster rate of change as thrust duration was shortened. This pattern was evident in paraspinal afferents with receptive fields both close and far from the midline. Paradoxically, spindle afferents were almost twice as sensitive to the 1-mm compared with the 2-mm amplitude thrust (6.2 vs. 3.3 spikes/s/mm/s). This latter finding may be related to the small versus large signal range properties of muscle spindles. CONCLUSIONS: The results indicate that the duration and amplitude of a spinal manipulation elicit a pattern of discharge from paraspinal muscle spindles different from slower mechanical inputs. Clinically, these parameters may be important determinants of an HVLA-SM's therapeutic benefit.     

Phosphorus Oxychloride in Organic Synthesis. Part 3: Synthesis of α-Benzoylaminocinnamic Acids

A new approach to the activation of reactants during the condensation of aromatic aldehydes with N-aroylglycines (acting as CH-acids) is described. The condensation reaction carried out on heating in phosphorus oxychloride leads to a high yield of 4-benzylideneoxazol-5-one derivatives. The hydrolysis of these intermediate products yields the target α-benzoylaminocinnamic acids. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 7, pp. 41 – 42, July, 2005.     

How Should Functionally Equivalent Drugs be Reimbursed?

Statutory reimbursement agencies as well as private insurers throughout member states of the Organization for Economic Cooperation and Development (OECD) reimburse the cost of medicines on the basis of criteria that include robust clinical evidence, budget impact analysis, and incremental cost effectiveness. The Centers for Medicare and Medicaid Services (CMS) in the US are no exception to this rule and are, in principle, seeking to maximize benefit for their Medicare enrollees, whilst ensuring reasonable drug outlays for the small number of drugs that they reimburse. This paper provides a retrospective analysis of the way two functionally equivalent drugs are treated for reimbursement purposes by the CMS; the period under consideration was 2001–3. The two drugs, epoetin-α and darbepoetin-α, are used for the treatment of anemia in renal failure and in patients receiving chemotherapy. By reviewing the publicly available pharmacological and clinical data of epoetin-α and darbepoetin-α, the paper confirms the two drugs’ functional equivalence, despite their structural differences. The implications of dose conversion ratios and costs to Medicare are subsequently explored. It is argued that the issue of dose equivalence between epoetin-α and darbepoetin-α has significant implications for patients, practitioners, and payors. A payor’s perspective is adopted in this respect, whereby clinical evidence and pricing data are used simultaneously. Based on the clinical evidence, a dose conversion ratio for epoetin-α:darbepoetin-α is established, which achieves a comparable clinical effect for the two drugs and this is set to be <254IU:1μg. The incremental costs to Medicare are calculated subsequently. The Average Wholesale Price and the Outpatient Prospective Payment System rule that Medicare uses to reimburse providers are used and suggest that treatment of cancer patients with chemotherapy-related anemia with epoetin-α would save Medicare an estimated $US600 million each year. Patients would also benefit significantly in terms of lower co-payments for epoetin-α. The evidence is supportive of the decision made by the CMS to reimburse the two drugs at the rate reflecting the achievement of comparable clinical effects and therefore reducing the pass-through payments for darbepoetin-α to zero for the 2002–3 fiscal year.