Diagnostic and therapeutic evaluation of 111In-vinorelbine-liposomes in a human colorectal carcinoma HT-29/luc-bearing animal model

Colorectal carcinoma is a highly prevalent and common cause of cancer in Taiwan. There is still no available cure for this malignant disease. To address this issue, we applied the multimodality of molecular imaging to explore the efficacy of diagnostic and therapeutic nanoradiopharmaceuticals in an animal model of human colorectal adenocarcinoma [colorectal cancer (CRC)] that stably expresses luciferase (luc) as a reporter. In this study, an in vivo therapeutic efficacy evaluation of dual-nanoliposome (100 nm in diameter) encaged vinorelbine (VNB) and (111)In-oxine on HT-29/luc mouse xenografts was carried out. HT-29/luc tumor cells were transplanted subcutaneously into male SCID mice. Multimodality of molecular imaging approaches including bioluminescence imaging (BLI), gamma scintigraphy, whole-body autoradiography (WBAR) and in vivo tumor growth tracing, histopathology and biochemistry/hematology analyses were applied on xenografted SCID mice to study the treatments with 6% polyethylene glycol (PEG) of (111)In-NanoX/VNB-liposomes. In vivo tumor growth tracing and BLI showed that tumor volume could be completely inhibited by the combination therapy with (111)In-VNB-liposomes and by chemotherapy with NanoX/VNB-liposomes (i.e., without Indium-111) (P<.01). The nuclear medicine images of gamma scintigraphy and WBAR also revealed the conspicuous inhibition of tumor growth by the combination therapy with (111)In-VNB-liposomes. Animal body weights, histopathology and biochemistry/hematology analyses were used to confirm the safety and feasibility of radiopharmaceuticals. A synergistic therapeutic effect on CRC xenografted SCID mice was proven by combining an Auger electron-emitting radioisotope (Indium-111) with an anticancer drug (VNB). This study further demonstrates the beneficial potential applications of multimodality molecular imaging as part of the diagnostic and therapeutic approaches available for the evaluation of new drugs and other strategic approaches to disease treatment.     

Early and late recipient graft function and donor outcome after laparoscopic vs open adult live donor nephrectomy for pediatric renal transplantation

BACKGROUND: Laparoscopically procured live donor kidney grafts are increasingly transplanted into pediatric recipients. The safety and efficacy of this changed surgical practice are unknown. HYPOTHESIS: Outcomes of laparoscopic vs open donor grafts in recipients 18 years and younger are equivalent. DESIGN AND SETTING: Retrospective review at an academic tertiary care referral center. PATIENTS: Eleven consecutive pediatric recipients of laparoscopically procured kidneys between April 1, 1997, and December 31, 2001, were pair matched for age with 11 recipients of openly procured kidneys between December 1, 1991, and March 31, 1997; the 22 adult donors were also studied. MAIN OUTCOME MEASURES: Recipients: surgical complications, graft function and survival. Donors: perioperative morbidity and length of hospital stay. RESULTS: Twenty (91%) of 22 kidneys were donated by a parent of the recipient. In recipients of laparoscopically procured grafts, we observed significantly lower creatinine clearances and higher creatinine levels on days 1, 4, and 6, but by 1 month, graft function was similar in both groups. No significant differences in surgical complications, delayed function, acute and chronic rejection, and graft survival rates were found. No laparoscopic or open donor required blood transfusion, reoperation, or hospital readmission. One laparoscopic donor (9%) was converted to open nephrectomy. For laparoscopic vs open donors, median operative time was longer (difference, 67 min; P =.08), but median postoperative length of stay was significantly shorter (3 vs 5 days; P =.02). CONCLUSIONS: Laparoscopic live donor nephrectomy has no adverse impact on pediatric recipient outcomes. For donors, the laparoscopic operation is safe and the hospital stay is shortened. These results support the continued use of laparoscopically procured live donor kidneys in pediatric renal transplantation.     

Scope and limitations of limb-sparing surgery in childhood sarcomas

The authors reviewed 43 children with high-grade sarcomas of bone and soft tissue who underwent surgery during the past 9 years. Twenty-six patients had osteosarcoma, 7 had Ewing sarcoma, and 10 had soft tissue sarcomas. Patients ranged in age from 4 months to 13 years. Mean follow-up period was 6 years. The feasibility of resection, results of local resection, and failure of local disease control were reviewed. Limb salvage was feasible in 81% of patients. Of the 35 patients undergoing limb salvage, margins were considered adequate in 88% and inadequate in 12%. Limb-sparing resection was not feasible in 19% of patients. Five patients (four with metastatic disease at presentation) did not undergo surgery and were given palliative care; three other patients underwent amputation. The decision of whether to proceed with limb salvage surgery must depend on the aggressiveness of the underlying tumor, its stage, the feasibility of obtaining tumor-free resection margins, and the response to neoadjuvant therapy.     

Assessment of the durability of robot-assisted laparoscopic sacrocolpopexy for treatment of vaginal vault prolapse

Transabdominal sacrocolpopexy has been shown, in multiple long-term studies of its success and durability, to be the definitive treatment option for post-hysterectomy vaginal vault prolapse. It is, however, associated with greater morbidity than vaginal repair. We describe a minimally invasive technique for vaginal vault prolapse repair and present our experience with a minimum of one-year follow-up. The surgical technique involves five laparoscopic ports—three for the da Vinci robot and two for the assistant. After appropriate dissection a polypropylene mesh is attached to the sacral promontory and to the vaginal apex by use of Gore-Tex sutures. The mesh material is then covered by the peritoneum. Patient analysis focused on complications, urinary continence, patient satisfaction, and morbidity, with a minimum of 12 months follow-up. Forty-two patients with post-hysterectomy vaginal vault prolapse underwent robot-assisted laparoscopic sacrocolpopexy at our institute and 35 have a minimum of 12 months follow-up, with a mean follow-up of 36 months (range 12–48) in the group. Mean age was 67 (47–83) years and mean operating time was 3.1 (2.15–4.75) h for the entire cohort. All but one patient were discharged home on postoperative day one; one patient left on postoperative day two. One developed recurrent grade three rectocele, one had recurrent vault prolapse, and two suffered from vaginal extrusion of mesh. All patients were satisfied with their outcome. The robot-assisted laparoscopic sacrocolpopexy is a minimally invasive technique for vaginal vault prolapse repair, combining the advantages of open sacrocolpopexy with the reduced morbidity of laparoscopy. We observed reduced hospital stay, low occurrence of complications, and high patient satisfaction, with a minimum of 1-year follow-up. Most importantly, the long-term results of the robotic repair are similar to those of open repair, but with significantly less morbidity.     

The association of anemia and hypoalbuminemia with accelerated decline in GFR among adolescents with chronic kidney disease

We sought to describe rates of kidney function decline and to identify modifiable risk factors for CKD progression in a multicenter prospective cohort study of adolescents with CKD aged 11 to 18 years seen semiannually for up to three years. Of the 23 subjects meeting inclusion criteria, the average estimated GFR was 51 ± 27 ml/min/1.73 m² (0.85 ± 0.45 ml/s/1.73 m²) at entry. The overall annualized decline in GFR was 5.6 ml/min/1.73 m² (0.093 ml/s/1.73 m²) per year (95% confidence interval [95% CI]: 1.9 to 9.3 [0.032 to 0.16]). The adjusted annualized decline in GFR was found to be accelerated in males, as well as among those over 15 years of age. The adjusted annualized decline in GFR was greater among those with either anemia (hematocrit below 36%), or hypoalbuminemia (albumin below 4 g/dl [40 g/L]). After adjustment, anemia was associated with an accelerated decline of 7.8 ml/min/1.73 m² (0.13 ml/s/1.73 m²) (95% CI: 3.3 to 12 [0.055 to 0.20]) and hypoalbuminemia was associated with an accelerated decline of 17 ml/min/1.73 m² (0.28 ml/s/1.73 m²) (95% CI: 11 to 22 [0.18 to 0.37]). Further study is needed to evaluate whether treatment of anemia or hypoalbuminemia, as outlined in current clinical care guidelines for CKD, may slow the progression of CKD in adolescents.     

Subchronic administration of L-DOPA to adult rats with a unilateral 6-hydroxydopamine lesion of dopamine neurons results in a sensitization of enhanced GABA release in the substantia nigra, pars reticulata

L-DOPA is the most effective pharmacological agent used for the symptomatic treatment of Parkinson's disease but long-term L-DOPA treatment induces involuntary abnormal movements such as dyskinesias. The present study, using in vivo microdialysis, investigated the effects of a single or subchronic administration of L-DOPA to adult rats with a unilateral 6-OHDA lesion of dopamine neurons on GABA release in the substantia nigra, pars reticulata (SNr). The results indicate that a challenge injection of L-DOPA (50 mg/kg, i.p.) significantly increases GABA levels in the SNr of rats treated with a daily repeated administration of L-DOPA (50 mg/kg, i.p.). Further statistical analysis between groups also showed that extracellular GABA levels were significantly higher in the subchronic L-DOPA group than in the group receiving only one injection of L-DOPA. These results show that the subchronic administration of L-DOPA results in a sensitization of enhanced extracellular GABA levels in the SNr.     

Neurocognitive profile in 22q11 deletion syndrome and schizophrenia

OBJECTIVE: Schizophrenia is associated with neurocognitive deficits, but its etiologic heterogeneity may complicate the delineation of a neurocognitive profile. Schizophrenia associated with 22q11 Deletion Syndrome (22qDS) represents a more genetically homogeneous subtype for study. We hypothesized that in adults with 22qDS the neurocognitive profiles would differ between those with and without schizophrenia. METHOD: Using a comprehensive battery of tests, we compared the neurocognitive performance profiles in those with schizophrenia (n=27; 14 M, 13 F; mean age=30.6 years, SD=7.7 years) and those with no history of psychosis (n=29; 16 M, 13 F; mean age=25.0 years, SD=9.0 years). RESULTS: The 22qDS groups with and without schizophrenia had similar mean estimated IQ (71.6, SD=8.2 and 74.8, SD=6.1, respectively) and academic achievement, however the neurocognitive profiles of the two groups differed significantly on multivariate analysis (F(24,31)=2.25, p=0.017). The group with schizophrenia performed significantly more poorly on tests of motor skills, verbal learning, and social cognition (effect sizes>or=0.8) after correction for multiple comparisons. Other tests, but not the attentional measures used, showed nominally significant differences. CONCLUSIONS: In adults with 22qDS, the pattern of neurocognitive differences between those with and without schizophrenia appears similar to that between patients with schizophrenia and controls. Attentional dysfunction may be a more general feature of 22qDS. The findings support 22qDS-schizophrenia as a genetic model for neurodevelopmental investigations of schizophrenia.     

Metacarpophalangeal joint arthroscopy: indications revisited

Arthroscopic surgery has become the gold standard for the diagnosis and treatment of major joint disorders. With advancement in arthroscopic technique, arthroscopy has become feasible in most human joints, even those as small as the finger joints. The metacarpophalangeal joint (MCPJ) can become spacious with simple traction, the intra-articular anatomy is simple, and its major structures can be easily visualized and identified. However, MCPJ arthroscopy has never been popular. This article describes our experience with MCPJ arthroscopy and seeks to establish its role in clinical practice.     

Pyogenic liver abscess complicated by endogenous endophthalmitis

Background: Endogenous endophthalmitis is an inflammation of ocular tissues that can lead to deterioration of and loss of vision. Rarely, this can complicate the course of a patient with pyogenic liver abscess. Methods: Over an 18‐month period, 68 patients were treated for pyogenic liver abscesses. Three patients, all of whom were male and with diabetes, were diagnosed with a Klebsiella pneumoniae liver abscess complicated by endogenous endophthalmitis. Open surgical or percutaneous drainage of the liver abscess was undertaken and the symptomology and outcome of the endophthalmitis reviewed. Results: There was no mortality in our series. Two patients presented with simultaneous abdominal and ocular symptoms and one patient had ocular symptoms 3 days after surgical drainage of the liver abscess. Despite aggressive treatment, all patients had permanent deterioration of visual function with one patient becoming blind and requiring evisceration of the infected eye. Conclusion: Ocular symptoms in patients treated for pyogenic abscesses must be dealt with urgently with an ophthalmologic consultation. Increased awareness of this complication and a high index of suspicion are paramount for salvage of visual function.