Prospective randomized trial of end-to-end versus side-to-side biliary reconstruction after orthotopic liver transplantation

BACKGROUND: Biliary reconstruction is the Achilles heel of liver transplantation. Side-to-side anastomosis of donor and recipient bile duct has been claimed to be superior to end-to-end anastomosis in uncontrolled studies. Methods: A total of 100 consecutive patients undergoing orthotopic liver transplantation were randomized after commencement of the transplant procedure to end-to-end or side-to-side anastomosis. No T tube drainage was employed. Endoscopic retrograde cholangiography was performed 2 weeks after transplantation and findings were reported by an experienced endoscopist as normal, leak or stricture. Median follow-up was 53 (range 35-63) months. RESULTS: Patient age, sex, the graft preservation time and indication for transplantation were similar in both groups. Sixty patients received end-to-end and 40 side-to-side anastomosis. Ten patients randomized to side-to-side anastomosis had an end-to-end procedure. The total number of biliary complications was similar in both groups (end-to-end 32 per cent versus side-to-side 30 per cent) as were the number of leaks (17 versus 18 per cent) and biliary strictures (15 versus 12 per cent). There was no difference in the number of biliary complications that required interventional treatment (22 per cent in both groups). CONCLUSION: Side-to-side and end-to-end biliary anastomosis at liver transplantation are equally effective.     

Preoperative magnetic resonance staging of rectal cancer with an endorectal coil and dynamic gadolinium enhancement

BACKGROUND: The aim of the study was to assess the value of endorectal coil magnetic resonance imaging (MRI) with gadolinium enhancement in the preoperative staging of rectal cancer. METHODS: In addition to standard evaluation, patients with rectal lesions were assessed by MRI obtained with a pelvic phased-array coil in combination with an endorectal coil. RESULTS: The study group comprised 29 patients with rectal cancer staged with an endorectal coil who had surgery without preoperative adjuvant therapy. In addition to standard T1- and T2-weighted images, dynamic contrast-enhanced images were acquired in all patients. Considerable interobserver variation was noted, particularly for pathological tumour stage pT1 or pT2 (kappa = 0.36). Compared with pathological findings, endorectal MRI correctly staged nine patients, overstaged 16 and understaged four. Whilst lymph node metastases were accurately detected in 70 per cent of patients, the positive predictive value was only 58 per cent. CONCLUSION: MR staging of rectal cancer with an endorectal coil and gadolinium enhancement is inaccurate for early tumours (stage T1 or T2) and is associated with a considerable degree of interobserver variation for individual scan sequences.     

Minimally invasive plate osteosynthesis: does percutaneous plating disrupt femoral blood supply less than the traditional technique?

OBJECTIVES/HYPOTHESIS: Proximal and distal femur fractures have traditionally been treated with open reduction and internal fixation through a standard lateral approach. New, "minimally invasive" internal fixation techniques, however, have been developed in an effort to devascularize the bone less than the traditional method. The purpose of this study was to determine whether a minimally invasive percutaneous plating technique better preserves bone vascularity relative to the traditional method by comparing the effect of the two approaches on the blood supply of the distal femur using silicone arterial dye injection in a cadaveric model. STUDY DESIGN/METHODS: Ten fresh human cadavers underwent lateral conventional plate osteosynthesis (CPO) through a standard lateral approach on one side and minimally invasive plate osteosynthesis (MIPO) through two three-centimeter incisions on the contralateral side. After injection of silicone dye, a dissection was performed bilaterally to identify the femoral perforating and nutrient arteries. RESULTS: All MIPO specimens showed intact perforating and nutrient arteries, whereas the CPO specimens had a variable incidence of vessel disruption. The MIPO group demonstrated better periosteal perfusion in each of the cadavers and improved medullary perfusion in 70 percent of the MIPO specimens compared with the CPO specimens. CONCLUSION: A percutaneous minimally invasive plating technique disrupts the femoral blood supply less than the traditional open method. Such minimally invasive methods may be more advantageous biologically than the traditional method.     

Prospective phase II trial of alternating intravesical Bacillus Calmette-Guérin (BCG) and interferon alpha IIB in the treatment and prevention of superficial transitional cell carcinoma of the urinary bladder: preliminary results

BACKGROUND AND OBJECTIVE: Evaluate the efficacy and toxicity of alternating intravesical instillation of Bacillus Calmette-Guerin(BCG) and Interferon alpha2-b (IFN) in the treatment and prevention of recurrence of superficial transitional cell carcinoma (TCC) of the urinary bladder. METHODS: Patients with Ta, T1 tumors and carcinoma in situ, either recurrent (TaG1, T1G1) or primary/recurrent TaG2 TaG3, T1G2, T1G3 and Tis (T: Tumor stage, G: grade) are eligible. All patients received intravesical BCG 81 mg on Weeks 1, 3, 5 and 7 and IFN 100 million units on Weeks 2, 4, 6 and 8. Cystoscopy performed 4 weeks after completion of therapy, and every 3 months thereafter. RESULTS: There was a total of 37 patients. Thirteen had TaG2, 13 T1G2, 1 T1G1, 4 TaG1, 1 TaG3, 3 T1G3 and 7 Tis (5 concurrent with other above tumors). Index lesion cleared in 7/10 patients. With a median follow-up of 26.2 month, 22 patients (59%) failed above therapy. Median time to treatment failure was 7 months. Seven, 6 and 9 patients recurred at a higher, lower and same stage or grade respectively. No grade 3 or 4 toxicity was encountered. CONCLUSIONS: Alternating intravesical BCG and IFN is effective and well tolerated therapy for superficial TCC of urinary bladder.     

Adding high-dose tamoxifen to CHOP does not influence response or survival in aggressive non-Hodgkin's lymphoma: an interim analysis of a randomized phase III trial

Purpose CHOP is the standard regimen currently used in the management of the majority of patients with aggressive non-Hodgkin's lymphoma (NHL). However, CHOP only produces 30–35% long-term survival. We hypothesized that adding high-dose tamoxifen, which is known to have multiple drug resistance-modulatory effects, to the CHOP regimen could increase the response rate, and consequently enhance the survival of patients with NHL. Patients and Methods In a prospective, controlled, and randomized study, eligible adult patients with aggressive NHL were randomized between CHOP only (Group I), or CHOP plus high-dose tamoxifen (Group II). The primary aim was to assess the effect of tamoxifen on complete response (CR) rate, with the secondary evaluation of tamoxifen potential impact on survival. The interim analysis of this study is presented. Results Fifty-one and forty-seven evaluable patients were randomized to Group I and Group II, respectively. The median age of all patients was 53y (range 18–78y). The two groups had comparable distributions of the pretreatment prognostic variables. The CR for patients in Group I was 80% (41 patients) as compared with 74% (35 patients) in Group II (P=0.48). Likewise, there was no apparent difference in the partial remission rates between the two groups (6% vs 15%, respectively). Of patients who initially attained CR, 15 (37%) and 10 (29%) subsequently relapsed in Groups II and I respectively (P=0.45). The NHL International Prognostic Index (IPI) was the only factor that predicted attaining CR. At the time of this interim analysis, the actuarial-estimated overall survival (OS) probability (±S.E.) for the entire population at 5 y was 58% (±6) with no survival difference between the two groups (P=0.51). Only attaining CR and the IPI predicted OS probability. The probability of remaining event-free at 5 y (±SE) for those achieving CR was 72% (±9), and there was no significant difference between the two treatment groups (P=0.68). Toxicity profile was similar in the two groups. Conclusion Based on this interim analysis, combining high-dose tamoxifen, as used in this study, with the CHOP regimen has failed to have any favorable effect on the outcome of patients with aggressive NHL, and therefore cannot be recommended for future trials.     

Effect of Schistosoma mansoni infection and treatment on drug metabolizing enzymes

The effect of Schistosoma mansoni infection on drug-metabolizing enzymes was investigated before and after treatment of S. mansoni-infected male albino mice with the antibilharzial drug praziquantel (CAS 55268-74-1). The drug was given in a total dose of 1000 mg/kg, and was administered at 500 mg/kg of body weight for two consecutive days each of 500 mg/kg of body weight. The drug was given 49 days after infection with 80 Egyptian strains of S. mansoni cercariae/mouse. The hepatic content of cytochrome P-450, cytochrome b-5 and NADPH cytochrome P-450 reductase were determined at 4, 8, 24, 72 h, one and two weeks after the second dose of treatment. The enzymes were determined in the microsomal fraction after homogenization and ultracentrifugation at 105,000 x g. The results indicate a marked decrease of most enzymes in the infected groups compared to normal controls. Two weeks after treatment there was an improvement of the level of most enzymes towards the normal values. The levels of liver function tests were also improved. Concerning the oogram pattern, there was a rapid change even after 8 h after the second dose of treatment. It was concluded that the antibilharzial drug could be considered as a safe drug with a rapid onset of action.     

The underdeveloped palate in ear,nose and throat practice

The purpose of this study is to assess the incidence of palatal underdevelopment in children undergoing tonsillectomy and adenoidectomy. Signs of underdevelopment were found in 24 out of 1,500 consecutive children admitted for tonsil and adenoid surgery (1.6%). Bifid uvula was found in 15 children (1%). Five palates showed deficiency in length or thickness (0.33%) and submucous cleft palate was found in 4 children (0.27%). The palatopharyngeal sphincter was often compensated and adequate. Middle ear disease attributable to Eustachian tube dysfunction, with or without infection, was found in the majority of the children with underdeveloped palate. Tonsil and adenoid surgery was modified according to the palatopharyngeal condition.     

Evidence for growth hormone (GH) autoregulation in pituitary somatotrophs in GH antagonist-transgenic mice and GH receptor-deficient mice

Growth hormone (GH) modulates the hypothalamic release of somatostatin and GH-releasing hormone; however, there has been no evidence of GH autoregulation on the pituitary somatotroph. To determine the effects of GH on its own regulation, we examined the pituitaries of giant transgenic mice expressing a GH agonist (E117L), dwarf transgenic mice expressing a GH antagonist (G119K), and dwarf mice devoid of the GH receptor/binding protein (GHR/BP). In the E117L transgenic mice, the number and distribution of pituitary GH-immunoreactive cells were unchanged from nontransgenic littermate controls; an ultrastructural examination revealed typical, densely granulated somatotrophs. In contrast, the pituitaries of the G119K mice contained both moderately granulated somatotrophs and a sparsely granulated (SG) population with well-developed synthetic organelles and a distinct juxtanuclear globular GH-staining pattern. GHR/BP-deficient mice exhibited a marked reduction in the intensity of cytoplasmic GH immunoreactivity; however, prominent GH staining in the juxtanuclear Golgi was seen. GH-immunoreactive cells were increased in number, and the reticulin network pattern was distorted; stains for proliferating cell nuclear antigen confirmed mild hyperplasia. Electron microscopy showed that the somatotrophs were hyperactive SG cells with prominent endoplasmic reticulum membranes, large Golgi complexes, and numerous mitochondria. These findings are consistent with synthetic and secretory hyperactivity in pituitary somatotrophs due to the reduced GH feedback regulation. The changes are most striking in animals that are devoid of GHR/BP and less marked in animals expressing a GH antagonist; both models had reduced insulin-like growth factor-I levels, but the more dramatic change in the GHR/BP animals can be explained by abrogated GH signaling. This represents the first evidence of direct GH feedback inhibition on pituitary somatotrophs, which may have implications for the use of GH analogs in different clinical settings.     

Efficacy of high-intensity laser therapy in the treatment of chronic neck pain: a randomized double-blind placebo-control trial

The aim of the study was to investigate the effect of high-intensity laser therapy (HILT) in treatment of patients with chronic neck pain (CNP) on cervical range of motion (ROM), pain, and functional activity. Sixty male patients participated in this study with mean (SD) age of 35.47 (4.18) years. Patients were randomly assigned into two groups and treated with HILT plus exercise (HILT?+?EX) and placebo laser plus exercise (PL?+?EX) in groups 1 and 2, respectively. The outcomes measured were cervical ROM, pain level by visual analog scale (VAS), and functional activity by neck disability index (NDI) score. Statistical analyses were performed to compare the differences between baseline and post-treatment. The level of statistical significance was set as p?<?0.05. Cervical ROM significantly increased after 6 weeks of treatment in all groups. VAS and NDI results showed significant decrease post-treatment in both groups. HILT?+?EX effectively increased cervical ROM and decreased VAS and NDI scores after 6 weeks of treatment compared to PL?+?EX. HILT?+?EX is an effective physical therapy modality for patients with CNP compared to PL?+?EX therapy. The combination of HILT?+?EX effectively increased cervical ROM, functional activity, and reduced pain after 6 weeks of treatment.     

Safety and usage of darbepoetin alfa in children with chronic kidney disease: prospective registry study

Background

Limited prospective data are available on the long-term safety of darbepoetin alfa (DA) for treating anemia in children with chronic kidney disease (CKD).

Methods

In this prospective, phase IV, observational registry study, children ≤16 years of age with CKD anemia and receiving DA were observed for ≤2 years. Adverse events (AEs), DA dosing, hemoglobin (Hb) concentrations, and transfusions were recorded.

Results

A total of 319 patients were included in the analysis (mean age, 9.1 years), 158 (49.5 %) of whom were on dialysis at study entry. Of 434 serious AEs reported in 162 children, the most common were peritonitis (10.0 %), gastroenteritis (6.0 %), and hypertension (4.1 %). Six patients (1.9 %) died (unrelated to DA). Four patients (1.3 %) experienced six serious adverse drug reactions. The geometric mean DA dose range was 1.4–2.0 μg/kg/month. Mean baseline Hb concentration was 11.1 g/dl; mean values for children receiving and not receiving dialysis at baseline ranged between 10.9 and 11.5 g/dl and 11.2–11.7 g/dl, respectively. Overall, 48 patients (15.0 %) received ≥1 transfusion.

Conclusions

No new safety signals for DA were identified in children receiving DA for CKD anemia for ≤2 years. Based on Hb concentrations and transfusion requirements, DA was effective at managing anemia in these patients.