Tramadol infusion for postthoracotomy pain relief: a placebo-controlled comparison with epidural morphine

We compared continuous IV tramadol as an alternative to neuraxial or systemic opioids for the management of postthoracotomy pain in a prospective, randomized, double-blinded, controlled study. General anesthesia was supplemented by thoracic epidural analgesia with 0.25% bupivacaine. At rib approximation, patients received one of the following: IV tramadol (150-mg bolus followed by infusion, total 450 mg/24 h, n = 29), epidural morphine (2 mg, then 0.2 mg/h, n = 30), or patient-controlled analgesia (PCA) morphine only (n = 30). All patients received PCA morphine and rescue morphine as necessary postoperatively. For the first 24 h, pain and sedation scores and respiratory, cardiovascular, and side effect measures were monitored. There was no significant difference in pain scores and PCA morphine use between tramadol and epidural morphine. Pain scores at rest and on coughing were lower in the Tramadol and Epidural Morphine groups than in the PCA Morphine group at various time points over the first 12 h. The Tramadol and Epidural Morphine groups used significantly less hourly PCA morphine than the PCA Morphine group at specific time points in the first 10 h. Vital capacities in the Tramadol group were significantly closer to baseline values at the 20-h point than in the PCA Morphine group. We conclude that an intraoperative bolus of tramadol followed by an infusion was as effective as epidural morphine and avoided the necessity of placing a thoracic epidural catheter. IMPLICATIONS: A prospective, randomized, double-blinded, placebo-controlled study of postthoracotomy pain relief showed that IV tramadol in the form of a bolus followed by continuous infusion was as effective as epidural morphine. The use of tramadol avoids the necessity of placing a thoracic epidural catheter.     

Controversies in Thyroid Pathology: Thyroid Capsule Invasion and Extrathyroidal Extension

Introduction and Design  

Endocrine pathologists, surgeons, and oncologists who manage patients with thyroid carcinomas confront many critical dilemmas. Controversies surrounding diagnostic criteria that distinguish benign from malignant thyroid follicular lesions have been brought to the attention of this community. In this article, we confront another controversy, the definition of a thyroid “capsule” to clarify what constitutes extrathyroidal extension (ETE) and its clinical significance in the management of patients with differentiated thyroid carcinomas.     

Continuous Preperitoneal Infusion of Ropivacaine Provides Effective Analgesia and Accelerates Recovery after Colorectal Surgery: A Randomized, Double-blind, Placebo-controlled Study

Background: Blockade of parietal nociceptive afferents by the use of continuous wound infiltration with local anesthetics may be beneficial in a multimodal approach to postoperative pain management after major surgery. The role of continuous preperitoneal infusion of ropivacaine for pain relief and postoperative recovery after open colorectal resections was evaluated in a randomized, double-blinded, placebo-controlled trial.

Methods: After obtaining written informed consents, a multiholed wound catheter was placed by the surgeon in the preperitoneal space at the end of surgery in patients scheduled to undergo elective open colorectal resection by midline incision. They were thereafter randomly assigned to receive through the catheter either 0.2% ropivacaine (10-ml bolus followed by an infusion of 10 ml/h during 48 h) or the same protocol with 0.9% NaCl. In addition, all patients received patient-controlled intravenous morphine analgesia.

Results: Twenty-one patients were evaluated in each group. Compared with preperitoneal saline, ropivacaine infusion reduced morphine consumption during the first 72 h and improved pain relief at rest during 12 h and while coughing during 48 h. Sleep quality was also better during the first two postoperative nights. Time to recovery of bowel function (74 +/- 19 vs. 105 +/- 54 h; P = 0.02) and duration of hospital stay (115 +/- 25 vs. 147 +/- 53 h; P = 0.02) were significantly reduced in the ropivacaine group. Ropivacaine plasma concentrations remained below the level of toxicity. No side effects were observed.     

Is parenthood associated with mental health?

BACKGROUND: Despite some reports on a potential link between parenthood and mental health, associations have not been systematically investigated yet. The present article provides prevalence rates of the most common mental disorders for parents and non-parents. Interactions between demographic and socio-economic variables, parental status and mental health are explored. METHODS: Data from the 1998/99 German Health Survey (GHS) and its Mental Health Supplement (GHS-MHS) were analysed using logistic regression models. Analyses were restricted to participants in the age group 18 to 49 (N=2,801). Mental disorders and syndromes were assessed with a standardized diagnostic interview (M-CIDI). RESULTS: Parenthood was associated with lower rates of psychiatric morbidity in general, and depressive and substance use disorders, in particular. The association between parental status and mental health was more distinct in men than in women, whereas partnership status moderated this relationship: An absence of partnership was associated with increased rates of all common mental disorders. Among non-parents, such a difference could not be found. Full-time employment, compared to part-time employment or unemployment, was linked to lower rates of the common mental disorders among fathers but not among mothers and non-parents. Age, education and income had no effects on the association between parental status and mental health. CONCLUSION: Parenthood is positively associated with mental health, particularly for men. Most differences can be found for depressive and substance use disorders. Partnership seems especially important for parents since it does not affect prevalence rates of mental disorders among non-parents.     

Loss of membrane localization and aberrant nuclear E-cadherin expression correlates with invasion in pancreatic endocrine tumors

Decrease in E-cadherin is considered a molecular event in dysfunction of the cell-cell adhesion system, triggering invasion and metastasis in many malignancies, including those of endocrine origin. In addition, alterations in the cadherin-catenin system may also be involved in tumorigenesis. E-cadherin and beta-catenin, components of the Wnt signal transduction pathway, may serve as a common switch in central processes that regulate cellular differentiation and growth. The purpose of this study was to examine if abnormalities of the Wnt signaling pathway, specifically, E-cadherin and beta-catenin, occur in pancreatic endocrine tumors (PETs) and correlate these with clinicopathologic parameters. Tissue microarrays were constructed from 57 cases with 4 to 14 cores measuring 1.0 mm from each case. Size of tumor, presence or absences of necrosis, gross invasiveness/demarcation, lymphovascular invasion, and lymph node involvement and liver metastasis were recorded. The mitotic count, expressed per 50 high power fields (HPF) and MIB-1 index of the entire tumor were assessed. All the tissue microarray blocks were stained with commercially available antibodies to E-cadherin (cytoplasmic and extracellular domains), beta-catenin, APC, and GSK-3beta. Twenty-seven were male patients and 30 female, ranging in age from 23 to 80 years (mean, 51.7 y). Six patients had MEN1 syndrome and 1 von Hippel Lindau disease. The tumors ranged in size from 0.8 to 9.8 cm with a mean of 3.4 cm. Sixteen patients had lymph node spread and 7 had liver metastasis. The Ki-67 labeling index ranged from 1% to 30% and the mitotic counts from 0 to 27 per 50 HPF. Thirty of 57 cases (52.6%) cases showed abnormal beta-catenin expression. Thirteen of the 16 cases with lymph node metastasis and all 7 cases with liver spread showed abnormalities of beta-catenin immunostaining. Only 2 cases showed nuclear beta-catenin. The average size of tumors with beta-catenin abnormalities was 4.8 cm. Thirty-four of the 57 (59.6%) cases showed loss of normal membranous immunoreactivity for both antibodies E-cadherin, including nuclear localization in 18 cases with the antibody that recognizes the cytoplasmic domain. E-cadherin decrease and/or loss was identical to beta-catenin with the same 13 cases showing nodal involvement and all 7 cases with liver metastasis displaying aberrant E-cadherin staining. Seven of the 18 cases with nuclear E-cadherin had lymph node spread and 3 liver metastases. The mean size of the 34 cases with abnormal E-cadherin expression was 4.4 cm, compared to the series mean of 3.4 cm. Interestingly, cases with nuclear E-cadherin had a mean size of 5.2 cm. beta-catenin and E-cadherin abnormalities did not correlate with other clinicopathological parameters. All 57 cases showed cytoplasmic immunoreactivity for APC, and cytoplasmic and nuclear positivity for GSK-3beta. APC and GSK-3beta did not show any correlation with beta-catenin or E-cadherin staining.Abnormalities of beta-catenin and E-cadherin immunoexpression are seen in the majority of PETs. Nuclear beta-catenin is rare in PET but nuclear E-cadherin, a previously unrecognized staining pattern in PETs was seen 18 of 57 cases with the antibody detecting the cytoplasmic fragment of E-cadherin. Aberrant expression of both beta-catenin and E-cadherin correlated strongly with lymph node spread and liver metastases.     

Occult tumor cells in lymph nodes as a predictor for tumor relapse in pancreatic adenocarcinoma

Background and aims Occurrence of tumor relapse is frequent in patients with pancreatic cancer despite the absence of residual tumor detectable at primary surgery and in histopathological examination. Therefore, it has to be assumed that current tumor staging procedures fail to identify minimal amounts of disseminated tumor cells, which might be precursors of subsequent metastatic relapse. The aim of this study was to assess the prognostic impact of minimal tumor cell spread detected in lymph nodes classified as “tumor-free” in routine histopathologic evaluation. Materials and methods A total of 154 “tumor-free” lymph nodes from 59 patients with pancreatic cancer who underwent intentionally curative tumor resection were examined by immunohistochemistry for disseminated tumor cells. Results Fifty (32.5%) of the “tumor-free” lymph nodes obtained from 36 (61%) patients displayed disseminated tumor cells. Multivariate survival analysis revealed that the presence of disseminated tumor cells in “tumor-free” lymph nodes is an independent prognostic factor for both a significantly reduced relapse-free survival (p = 0.03) and overall survival (p = 0.02). Conclusions The frequent occurrence and prognostic impact of immunohistochemically identifiable disseminated tumor cells in lymph nodes of patients with operable pancreatic cancer supports the need for a refined staging system of excised lymph nodes, which should include immunohistochemical examination.     

Contrast in the efficacy of hDAF mouse hearts between ex vivo perfusion and transplantation into primates

Abstract: In recent experiments, in which we compared hDAF transgenic rat hearts perfused with 15% human serum in the Langendorff device and hDAF rat hearts transplanted into cynomolgus monkeys, we demonstrated that in the ex vivo heart perfusion model both homozygous and heterozygous hDAF hearts survived longer as nontransgenic controls. Surprisingly, we found that only homozygous hDAF hearts were protected against hyperacute rejection in vivo. The first aim of this study was to determine whether perfusion of mouse hearts with higher human serum concentrations or human blood might explain some of the differences found in survival time of the recently performed experiments with rat heart xenografts. Secondly, we investigated whether the observed differences in survival times of rat xenografts between in vivo and ex vivo transplantation would also hold for mouse hearts transgenic for hDAF. An ex vivo model was used to perfuse hDAF mouse hearts and controls with human serum or blood, and hDAF transgenic hearts and controls were transplanted into cynomolgus monkeys. hDAF transgenic mouse hearts survived significantly longer than their controls when perfused with 15% human serum, but no difference was found when 30% human serum was used, or when these hearts were transplanted into cynomolgus monkeys. However, in both the in vivo and ex vivo models the amount of PMNs adhering to the vascular endothelium was significantly lower in hDAF transgenes as compared with their controls. In conclusion, in the ex vivo situation, the efficacy of hDAF transgenesis in preventing HAR is limited by serum complement concentration.     

Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation

BACKGROUND: Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship. METHODS: Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate. RESULTS: At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r2 = 0.20, p<0.001) and ventilation heterogeneity (partial r2 = 0.39, p<0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009) and airway hyperresponsiveness (p<0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r2 = 0.64, p<0.001). CONCLUSIONS: Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long-term outcomes.     

Completion thyroidectomy versus total thyroidectomy: is there a difference in complication rates? An analysis of 350 patients

BACKGROUND: This study compared our experience with completion thyroidectomy (CT) and total thyroidectomy (TT) in the management of well-differentiated thyroid cancer (WDTC). We compared complication rates and analyzed the implications of the intraoperative management of the parathyroid glands. STUDY DESIGN: We performed a retrospective cohort study comparing outcomes between patients undergoing CT and TT between January 1994 and December 2004. All patients had surgery for either suspected or confirmed WDTC on fine-needle aspiration. RESULTS: There were 201 CTs and 149 TTs. Mean hospital stays were 4.5 and 3.5 days for the CT and TT groups, respectively (p=0.001). Temporary recurrent laryngeal nerve paresis occurred in 2.0% (4 of 201) and 3.3% (5 of 149) of patients in the CT and TT groups, respectively. There was one (0.5%) case of permanent recurrent laryngeal nerve paralysis in the CT group. Permanent hypoparathyroidism rates were 2.5% and 3.3% in the CT and TT groups, respectively. There was no difference between the two groups in terms of total numbers of parathyroid glands autotransplanted (p=0.63) or present in the specimen (p=0.26). CONCLUSIONS: Completion thyroidectomy is a safe and appropriate option in the management of select cases of WDTC in which a definitive preoperative or intraoperative diagnosis is not available. But it requires a longer hospitalization, so it has implications for both hospital resources and the patients involved.