Pegylated liposomal doxorubicin hydrochloride (PLD) and paclitaxel in recurrent or metastatic head and neck carcinoma: a phase I/II study conducted by the Hellenic Cooperative Oncology Group (HeCOG)

A phase I pharmacokinetics and dose-finding study and a phase II study of the combination of pegylated liposomal doxorubicin HCl (PLD) and paclitaxel were conducted in patients with recurrent or metastatic head and neck cancer (HNC). Sixty patients with recurrent or metastatic disease were enrolled in the study: 11 patients in the phase I study and 49 patients in the phase II study. In the phase I study, the initial dose level of PLD was 35 mg/m as a 1-h infusion with escalating increments of 5 mg/m until the maximum tolerated dose (MTD) was reached. A fixed dose of paclitaxel (175 mg/m) was administered as a 3-h infusion. The combination was administered every 28 days. Pharmacokinetic studies performed on 10 patients indicated that the sequence of drug administration did not cause clinically significant modifications in the pharmacokinetics of either drug. The MTD for PLD was 45 mg/m (dose level 3) and the dose-limiting toxicity was febrile neutropenia, occurring in three of five patients. The phase II dose of PLD was 40 mg/m (dose level 2) and a total of 214 cycles were delivered. Grade 3 or 4 neutropenia was observed in 26% patients and febrile neutropenia occurred in 16% of patients. Grade 3 palmar-plantar erythrodysesthesia (PPE) was recorded in only one patient. The overall response rate was 28% for patients with non-nasopharyngeal tumors [95% confidence interval (CI) 15-45%] and 28.6% for the study population (95% CI 17-43%). The median survival for the study population was 9.7 months; 1-year survival was 38%. We conclude that the recommended dose for the combination of PLD and paclitaxel is 40 and 175 mg/m every 28 days, without granulocyte colony stimulating factor support. The combination of paclitaxel with PLD demonstrated activity in recurrent or metastatic HNC, a favorable toxicity profile and relative ease of administration.     

Immunohistochemical expression of metalloproteinases MMP-2 and MMP-9 in abdominal aortic aneurysms: correlation with symptoms and aortic diameter

Our purpose was to investigate the expression of matrix metalloproteinase (MMP)-2 and -9 in all types of abdominal aortic aneurysms (AAA): symptomatic, asymptomatic, and ruptured. MMP-2 and -9 activity was investigated in surgical samples from the arterior wall of 46 AAA, using a standard immunohistochemical technique. The MMP-9 activity was significantly higher in large AAA (>6 cm), but there was no relation between AAA size and MMP-2 activity. Neither MMP-2 nor MMP-9 were related with AAA rupture, other complications or symptoms. The MMP-9 activity in AAA is a determinant of the aneurysm size, but it is not related to clinical manifestations.     

Allogeneic blood transfusion requirements after minimally invasive versus conventional aortic valve replacement: a risk-adjusted analysis

BACKGROUND: Aortic valve replacement (AVR) through a partial sternotomy (mini-AVR) has been suggested to significantly reduce postoperative morbidity compared with conventional AVR. This study sought to investigate whether mini-AVR patients require fewer transfusions than patients who had conventional AVR. METHODS: Of 511 patients who had AVR, 56 had mini-AVR and 455 had conventional AVR. A matched-case logistic regression analysis was used to adjust for these imbalances between groups. RESULTS: No patient in the mini-AVR cohort required conversion to a conventional AVR. Cardiopulmonary bypass time was longer in the mini-AVR group compared with the conventional AVR group, with a median of 102 minutes (range, 78 to 119 minutes) versus 75 minutes (range, 61 to 96 minutes; p < 0.01) in the conventional AVR group. A total of 31 patients (55%) in the mini-AVR group and 336 patients (74%) in the conventional sternotomy group required transfusions during their hospital stay (p < 0.01). After adjusting for differences in preoperative risk factors, year of operation, and surgeon, by matching on propensity score, the differences were not statistically significant (odds ratio = 0.84, 95% confidence interval = 0.40 to 1.75, p = 0.63). CONCLUSIONS: Mini-AVR produces better wound cosmesis and less surgical trauma but requires more time to perform. Matched-case analysis failed to show a significant difference in blood transfusion requirements after mini-AVR compared with the conventional AVR approach.     

Silastic drains vs conventional chest tubes after coronary artery bypass

STUDY OBJECTIVES: To investigate differences in drainage amounts and early clinical outcomes associated with the use of Silastic drains, as compared with the conventional chest tube after coronary artery bypass grafting (CABG). DESIGN: Retrospective nonrandomized case control study. SETTING: A tertiary teaching hospital. Patients and participants: Outcome data from 554 patients who underwent postoperative pericardial decompression using small Silastic drains were compared with those from 556 patients who had conventional chest tubes after first-time CABG at our institution between January 1 and August 1, 2000. Measurement and results: Univariate analysis of preoperative characteristics was used to ensure similarity between the two patient groups. Operative mortality, mediastinitis, reoperation for bleeding, and early and late cardiac tamponade occurred in 9 patients (1.6%), 6 patients (1.1%), 6 patients (1.1%), 6 patients (1.1%), and 1 patient (0.2%), respectively, in the Silastic drain group, compared with 11 patients (2.0%), 9 patients (1.6%), 4 patients (0.7%), 2 patients (0.4%), and 6 patients (1.1%) in the conventional group. No statistically significant differences between the two drains were identified. Drainage amounts (mean +/- SD) were 552.2 +/- 281.8 mL and 548.8 mL +/- 328.7 mL for the Silastic and conventional groups, respectively (p = 0.51). Postoperative length of stay was longer for the conventional chest tube group (median, 5 d; range, 1 to 119 d) when compared to the Silastic drain group (median, 4 d; range, 1 to 66 d; p = 0.01). CONCLUSIONS: We demonstrated that small Silastic drains are equally as effective as the conventional, large-bore chest tubes after CABG with no significant risk of bleeding or pericardial tamponade. Additionally, use of Silastic drains allows more mobility than the conventional chest tubes. As a result of this study, there was a change in our clinical practice toward the exclusive use of Silastic drains after all cardiac surgical procedures.     

Infected femoral artery pseudoaneurysm in drug addicts: the beneficial use of the internal iliac artery for arterial reconstruction

BACKGROUND: Infected femoral artery pseudoaneurysm (IFAP) is a severe complication in parenteral drug abusers, with difficult and controversial management. Ligation alone without revascularization is frequently associated with later intermittent claudication and limb amputation. Furthermore, arterial reconstruction with a synthetic or venous conduit is limited because of a contaminated field and, often, unavailability of autologous venous grafts. In this study, we present our experience with the internal iliac artery (IIA) as a graft for arterial reconstruction after IFAP excision in these patients. METHODS: Data of 14 consecutive patients who presented with IFAP secondary to parenteral drug abuse from 2001 to 2005 were analyzed. Twelve patients (85.7%) were male. The median age was 27 years (range, 19-42 years). In 13 cases, the IFAP involved the common femoral artery, and in 1 case it involved the profunda femoris artery (PFA). In nine patients, we used the IIA for arterial reconstruction (five as a patch and four as an interposition graft), whereas in two patients the arterial deficit was repaired with a great saphenous vein patch. In two cases, an extra-anatomic bypass with a synthetic polytetrafluoroethylene graft was performed. In one patient, the pseudoaneurysm involved the PFA and was treated with excision and ligation of the PFA. RESULTS: All nine patients who underwent revascularization with the use of IIA were free of claudication symptoms. None of them experienced any perioperative complications, had signs of reinfection, or required limb amputation during the follow-up period (median, 19 months; range, 4-52 months). Regarding the remaining five patients, one died 25 days after surgery because of multiorgan failure, and one underwent reoperation because of proximal anastomotic rupture of a synthetic graft. The latter patient finally underwent a transmetatarsal amputation. CONCLUSIONS: The use of IIA for arterial reconstruction after IFAP excision in drug abusers is safe and effective. These preliminary results indicate that the implementation of this technique offers many advantages compared with traditional treatment options.     

Tyrosine hydroxylase deficiency in three Greek patients with a common ancestral mutation

We present the clinical, biochemical, and molecular findings of three Greek patients with tyrosine hydroxylase (TH) deficiency. All patients presented with a severe clinical phenotype characterized by prominent motor delay, infantile parkinsonism, oculogyric crises, and signs of autonomic dysfunction. Cerebrospinal fluid analysis disclosed reduced dopamine metabolites and normal pterins. Response to levodopa was favorable though not dramatic. All patients were homozygous for a previously reported mutation (p.L236P). SNP haplotype analysis was consistent with a common ancestral mutation, thus indicating a founder effect in Greek patients with TH deficiency. © 2010 Movement Disorder Society     

Surgical training in the 48-h week: a novel simulation and educational tool. From amateur golfer to professional pilot

Introduction: Compliance with the European Working Time Directive has made obvious the need for a surgical skills training system that will produce surgeons fast and reliably. We have previously proposed a model for objective assessment of surgical dexterity. In this paper we aim to place an updated version of that model into the context of a holistic approach on assessment of a trainee's progress towards becoming an independently operating surgeon. Methods: The PAR matrix breaks down an operation into clearly defined skills that need to be successively acquired. It consists of a 3 × 6 table depicting 18 skill-goals. The y-axis is divided into six levels and the x-axis into three columns. The initials of the three skills on each level form the acronym PAR. Each skill is further graded from 1 to 3 (unsatisfactory, competent, good). The levels are: Level 1 – posture, address, relaxation; Level 2 – pick-up, airtime, rotation; Level 3 – placing, angles, rhythm; Level 4 – precision, adaptability, reproducibility; Level 5 – pace, awareness, relations; Level 6 – planning, announce, review/reflexion. Results: The format of the PAR model is such that it allows trainer and trainee to objectively assess progress, identify deficiencies and strengths and formulate an appropriate plan of action. Conclusion: Ergonomics and crew resource management skills are essential for a safe operating environment. The PAR matrix may prove helpful in selection of trainees and revalidation of trainee surgeons as a competence and performance testing method, placed in the appropriate training curriculum.     

Partially covered vs uncovered sphincterotome and post-endoscopic sphincterotomy bleeding

AIM: To prospectively compare partially covered vs uncovered sphincterotome use on post-endoscopic biliary sphincterotomy (ES) hemorrhage and other complications. METHODS: All patients referred for therapeutic endoscopic retrograde cholangiopancreatography (ERCP) were randomly assigned to undergo ES either with a partially covered or an uncovered sphincterotome. Both patient and technical risk factors contributing to the development of post-ES bleeding were recorded and analyzed. The characteristics of blee...     

Hydrogen peroxide is produced by E. coli challenged haemocytes and regulates phagocytosis, in the medfly Ceratitis capitata. The active role of superoxide dismutase

Hydrogen peroxide (H₂O₂) participates as a second messenger in cell signaling. In this paper, the role of H₂O₂ was investigated, in Escherichia coli phagocytosis by the haemocytes of the medfly Ceratitis capitata. Block of H₂O₂ synthesis by specific enzymic inhibitors, namely N-ethylmaleimide (NEM) for NADPH oxidase and diethyldithiocarbamate (DDC) for SOD, resulted in the increase of E. coli phagocytosis. Immunoblot analysis, flow cytometry and confocal microscopy, revealed the constitutive expression of SOD, in the medfly haemocytes. Phagocytosis increased by small interfering RNA (siRNA) for SOD, revealing the active involvement of SOD and H₂O₂. Immunoblot analysis showed an increase of the ERK1/2 phosphorylation, in the presence of the above H₂O₂ synthesis enzymic inhibitors. In addition, confocal microscopy showed no co-localization of SOD with β integrin subunit. It appears that SOD participates in the regulation of bacterial phagocytosis, due to involvement of the produced H₂O₂ in the differential phosphorylation of MAP kinases.     

Biliary tract malignancy and abnormal pancreaticobiliary junction in a Western population

BACKGROUND AND AIM: Abnormal pancreaticobiliary junction is a rare congenital disorder in which the junction of biliary and pancreatic duct is located outside the duodenal wall and forms a long common channel. The disorder has been associated with a high incidence of gallbladder cancer in Japanese studies. The aim of this study was to assess the frequency of abnormal pancreaticobiliary junction in a Western population and its association with biliary tract malignancies. METHODS: All endoscopic retrograde cholangiopancreatography examinations of 82 consecutive patients with gallbladder carcinoma or biliary duct cancer treated at Baylor University during a period of 10 years were analyzed. A further 220 consecutive patients with normal films or non-malignant pancreaticobiliary disease acted as controls. RESULTS: Fifty-eight (70.7%) patients were found to have adequate imaging of junction and were included in the analysis. These included 37 patients with common bile duct carcinoma and 21 with gallbladder carcinoma. Abnormal pancreaticobiliary junction (common channel > or =8 mm) was observed in 44.8% patients with biliary tract carcinoma compared to 6.2% of controls (P < 0.01). Eighteen had type I abnormality and eight type II. Seven patients had a cystic dilatation of the common bile duct, all with type I abnormality. Mean overall survival was 9.5 months. Survival did not differ significantly between patients with normal and abnormal junctions (P = 0.1). CONCLUSIONS: The results suggest a close association between the anatomy of the distal ends of the common bile duct and main pancreatic duct and development of biliary tract carcinoma in Western populations.