Effect of internal biliary drainage on plasma levels of endotoxin,cytokines, and C-reactive protein in patients with obstructive jaundice

Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice. We conducted a prospective longitudinal, before-after trial in our 600-bed teaching hospital. Twenty-four patients with obstructive jaundice were investigated, 11 with benign obstruction and 13 with malignant disease. Endoscopic internal biliary drainage was performed in all patients (7 by papillotomy and 17 by endoprostheses). Endotoxin, tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), nitric oxide production, and C-reactive protein (CRP) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished. Bile cultures were obtained before and at the time of drainage. Endotoxin, IL-6, TNF-a, and CRP were significantly higher in patients with cancer. After internal drainage, endotoxin (11.4 vs. 2 EU/L; p <0.05), TNF-a (87.5 vs. 48 pg/ml; p = 0.03), and IL-6 (324 vs. 232 pg/ml; p <0.05) plasma levels decreased significantly in the early postdrainage period in patients with cancer. Endotoxin, cytokines, as well as the CRP plasma values, however, increased again on day 7 after drainage. This trend was less marked in patients with benign obstruction. Patients with positive bile cultures after drainage displayed higher levels of CRP (115 vs. 62 mg/L; p = 0.03), IL-6 (598 vs. 330 pg/ml; p = 0.04), and endotoxin (10.6 vs. 4.8 EU/L; p = 0.02) than those with negative bile cultures. Biliary tract obstruction is associated with an increase in endotoxin levels, a positive acute-phase response, and plasma cytokine elevation. After biliary drainage a transitory improvement of these alterations was observed, although values remained high 1 week postdrainage. These findings were associated with positive bile cultures.     

Glial cell line-derived neurotrophic factor promotes the arborization of cultured striatal neurons through the p42/p44 mitogen-activated protein kinase pathway

Glial cell line-derived neurotrophic factor (GDNF) promotes the survival or differentiation of several types of neurons. This study examines GDNF-induced signal transduction and biological effects in cultured striatal neurons. Results show that GDNF addition to striatal cultures transiently increased the protein levels of phosphorylated p42/p44, but did not change the levels of phosphorylated Akt. GDNF effects on phosphorylated p42/p44 levels were blocked by the mitogen-activated protein kinase (MAPK) pathway specific inhibitors (PD98059 and U0126). Activation of the p42/p44 MAPK pathway by GDNF led to an increase in the degree of dendritic arborization and axon length of both GABA- and calbindin-positive neurons but had no effect on their survival and maturation. These GDNF-mediated effects were suppressed in the presence of the inhibitor of the MAPK pathway (PD98059). Furthermore, the addition of the phosphatidylinositol 3-kinase pathway specific inhibitor (LY294002) blocked GDNF-mediated striatal cell differentiation suggesting that the basal activity of this pathway is needed for the effects of GDNF. Our results indicate that treatment of cultured striatal cells with GDNF specifically activates the p42/p44 MAPK pathway, leading to an increase in the arborization of GABA- and calbindin-positive neurons.     

Pretherapeutic Extraperitoneal Laparoscopic Staging of Bulky or Locally Advanced Cervical Cancer

Background

To assess the safety, feasibility, and impact on survival of extraperitoneal para-aortic lymphadenectomy in the staging of patients with bulky or locally advanced cervical cancer.

Materials and Methods

Between August 2001 and October 2009, 87 consecutive patients (median age 51 years) with bulky or locally advanced cervical cancer underwent extraperitoneal laparoscopic infrarenal aortic and common iliac dissection as a pretherapeutic staging procedure. Data on pathologic findings, details of surgery, postoperative complications, and disease status at follow-up were collected.

Results

The median operating time was 150 min (range 60–255 min). The mean (± standard deviation) para-aortic nodal yield was 15.5 ± 8.1 (range 4–62). In none of the patients, conversion to the transperitoneal approach or laparotomy was necessary. Histological examination revealed metastasis in 13 patients (macroscopic disease 10, microscopic disease 3). After a median follow-up of 33.4 months (range 13.3–65.9 months), 73.6% of patients were free of disease and 1.1% were alive with disease, 19.5% died from cervical cancer, and 3.3% died from other causes. After a follow-up of 3 years, no deaths or recurrences were documented, with an overall survival rate of 74.8% (95% CI 62.8%–83.4%) and disease-free survival of 86% (95% CI 74.7%–92.5%). There were no significant differences in overall survival and disease-free survival between patients with positive and negative para-aortic lymph nodes.

Conclusion

The extraperitoneal laparoscopic para-aortic lymphadenectomy for pretherapeutic surgical staging in cervical cancer is a safe and feasible procedure that should be considered as a tool to identify lymph node positive patients who require extended-field radiation and/or chemotherapy.     

Treatment of the open abdomen with topical negative pressure therapy: a retrospective study of 46 cases

The open abdomen is an ongoing challenge for professionals engaged in its treatment. The change in the integrity of the abdominal wall, the loss of fluids, heat and proteins and contamination of the wound are the main problems. The objective of this article is to describe our experience using the abdominal dressing vacuum‐assisted closure therapy in treatment of the open abdomen. Since December 2006, all patients requiring treatment with the open abdomen technique have been treated with the abdominal dressing system and vacuum‐assisted closure therapy (VAC^® KCI, San Antonio, USA). The results obtained with this technique in non traumatic patients are analysed herein. The abdominal dressing system was used on 46 patients in the period between January 2006 and December 2009, with a mean 63 years old (29–80), with a gender distribution of 33 men (72%) and 13 women (28%). Closure of the abdominal wall was possible in 24 patients, 5 of which were primary in the recent postoperative phase, 5 had primary suture of the fascia and application of the supra‐aponeurotic prosthesis and 14 had closure of the abdominal wall with a composite polytetrafluoroethylene (PTFE) and polypropylene mesh. Second intention closure took place in the remaining 22 patients (48%), as their conditions did not allow primary closure. The mean treatment time with abdominal dressing was 26 days (6–92) with an average of eight changes per patient. The abdominal dressing topical negative pressure system is a useful option for consideration in the event of needing to leaves the abdomen open. It stabilises the abdominal wall and quantifies and collects exudate from the wound, protects the intra‐abdominal viscera and keeps the fascia intact and the cutaneous plane for subsequent closure of the wall.     

Voice quality after CO2 laser cordectomy—What can we really expect?

BACKGROUND: Endoscopic management of laryngeal carcinoma has gained popularity among laryngologists based on the good oncologic and functional results. We evaluated the voice quality after laser cordectomy for early glottic cancer in a variety of vocal situations and its relation with the extension of resection and the age. METHODS: We conducted a cross-sectional study of voice quality in 42 consecutive male patients treated for T1 glottic carcinoma with laser cordectomy. Patients were compared with 21 controls. Voice quality was self-assessed by the patients. Perceptual analysis was done by a speech pathologist on a running speech sample [GRBAS (grade, roughness, breathiness, asthenicity, strain)]. Acoustic analysis included fundamental frequency (F0), jitter, shimmer, noise to harmonic ratio (N/H), and maximum phonation time (MPT) on the sustained vowels /a/ and /i/, and on various running speech voice samples. RESULTS: Distribution of the patients included in the study by T classification was as follows: Tis, n = 2 (4.8%); T1a, n = 35 (83.3%); and T1b, n = 5 (11.9%). Cordectomy types were: (I), 14%; (II), 26%; (III), 21%; and (V), 38%. Voice improved in almost 60% of patients, returning to normal in 45%. GRBAS showed significant differences between patients and controls and correlated with type of cordectomy. Acoustic analysis showed significant differences in F0, and jitter, with smaller differences in shimmer, N/H, and MPT. CONCLUSION: Voice quality after laser cordectomy differs from controls, but improves in a majority of patients after the surgery, with almost 50% of patients with subjective normal or near normal voice. Voice quality depends on type of cordectomy.     

Transcervical carotid stenting with flow reversal is safe in octogenarians: a preliminary safety study

BACKGROUND: The use of carotid stenting in octogenarian patients is controversial; some authors consider this population at high risk for the procedure. Anatomic vascular complexity may be an important reason for the high reported rates of periprocedural thromboembolic complications. Transcervical carotid angioplasty and stenting (TCS) with flow reversal avoids aortic arch instrumentation. In this study, we analyzed our experience with TCS in octogenarian patients and compared the results with those of carotid endarterectomy (CEA) in the same age group in terms of safety. METHODS: The study included 81 patients, > or =80 years, a retrospective cohort of 45 consecutive patients treated with CEA (January 2002 to January 2005), and a prospective cohort of 36 consecutive patients treated with TCS with protective flow reversal (January 2005 to January 2007). Patients were considered symptomatic according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Stenting indication was established on the SAPPHIRE criteria. General anesthesia was used in patients undergoing CEA, and local anesthesia in those receiving TCS. Primary endpoints were: stroke, death, or acute myocardial infarction within 30 days. Secondary endpoints were peripheral nerve paralysis and cervical hematoma. Statistical significance for between-group differences was assessed by Pearson chi(2) or Fisher exact test, and Student t test. A P value of <.05 was considered statistically significant. Follow-up was limited to 30 days. RESULTS: Baseline epidemiological characteristics and revascularization indications were similar between both groups. Mean age was significantly higher in the TCS group (83.5 +/- 3.35) than the CEA group (81.7 +/- 1.55) (P = .004). Percentage of symptomatic lesions was similar: 30.6% in TCS vs 44.4% in CEA (P = .2). Comorbid conditions (respiratory or cardiac) were more frequent in TCS group (61.6% vs 26.6%; P = .002). There were no significant differences between groups for the primary endpoints: 4.4% (one stroke, one acute myocardial infarction) for CEA vs 0% for TCS (P = .5). Among CEA patients, there were two peripheral nerve palsies (4.4%) and one cervical hematoma (2.2%); there were no such complications with TCS (P = .5 and P = 1, respectively). In one asymptomatic TCS patient, Doppler study at 24 hours following the procedure showed a common carotid artery dissection, which was treated by a common carotid to internal carotid bypass. CONCLUSIONS: In this preliminary experience, transcervical carotid angioplasty and stenting with flow reversal for cerebral protection was as safe at short term as carotid endarterectomy in octogenarian patients, who additionally had considerable comorbidity; thus, it may be possible to extend the indications for carotid revascularization in this population. Studies in larger patient series are required to confirm the trends observed in this study.     

Combined surgery for the treatment of bilateral subclavian artery aneurysm in Marfan syndrome

Large bilateral aneurysm of the subclavian artery is an infrequent entity that can progress to thrombosis, embolization, or rupture if left untreated. Treatment consists of exclusion of the aneurysm by an endovascular procedure or open surgery. We present a case of large bilateral subclavian artery aneurysm in a patient with Marfan syndrome that was treated by a combination of endovascular and conventional surgery. This therapeutic approach provided good results for patency with lower morbidity and mortality.     

Protease inhibitor monotherapy is associated with a higher level of monocyte activation,bacterial translocation and inflammation

Introduction

Monotherapy with protease-inhibitors (MPI) may be an alternative to cART for HIV treatment. We assessed the impact of this strategy on immune activation, bacterial translocation and inflammation.

Methods

We performed a cross-sectional study comparing patients on successful MPI (n=40) with patients on cART (n=20). Activation, senescence, exhaustion and differentiation stage in CD4+ and CD8+ T lymphocyte subsets, markers of monocyte activation, microbial translocation, inflammation, coagulation and low-level viremia were assessed.

Results

CD4+ or CD8+ T lymphocyte subset parameters were not significantly different between both groups. Conversely, as compared with triple cART, MPI patients showed a higher proportion of activated monocytes (CD14+ CD16−CD163+ cells, p=0.031), soluble markers of monocyte activation (sCD14 p=0.004, sCD163 p=0.002), microbial translocation (lipopolysaccharide (LPS)-binding protein; LBP p=0.07), inflammation (IL-6 p=0.04) and low-level viremia (p=0.035). In a multivariate model, a higher level of CD14+ CD16−CD163+ cells and sCD14, and presence of very low-level viremia were independently associated with MPI. Monocyte activation was independently associated with markers of inflammation (IL-6, p=0.006), microbial translocation (LBP, p=0.01) and low-level viremia (p=0.01).

Conclusions

Patients on MPI showed a higher level of monocyte activation than patients on standard therapy. Microbial translocation and low-level viremia were associated with the high level of monocyte activation observed in patients on MPI. The long-term clinical consequences of these findings should be assessed.