Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4-7 cm

OBJECTIVE: To compare the outcomes of patients who had a elective partial nephrectomy (PN) or radical nephrectomy (RN) for clear cell renal cell carcinoma (RCC) of 4-7 cm. PATIENTS AND METHODS: From March 1998 to July 2004, 45 and 151 patients underwent PN and RN, respectively, for clear cell RCC. A multivariate Cox model was constructed for disease-free survival with adjustment for markers of disease severity, and a propensity-score approach used as a confirmatory analysis. RESULTS: In the PN and RN cohorts the treatment failed in one and 20 patients, respectively; the median follow-up was 21 months. The hazard ratio (95% confidence interval) for PN after adjusting for disease severity was 0.36 (0.05-2.82; P = 0.3). Using planned PN as a predictor (intent-to-treat analysis) the hazard ratio was 1.06 (0.32-3.53; P = 0.9). In the propensity-score model, planned PN was associated with a hazard ratio of 1.75 (0.50-6.14; P = 0.4). The serum creatinine level 3 months after surgery was significantly lower in patients who had PN, with a difference between the means of 0.36 (0.23-0.48; P < 0.001). CONCLUSIONS: Renal function was preserved after PN for 4-7 cm clear cell RCC tumours. When comparing the outcomes of PN and RN it is important to consider the intended operation as an independent variable. There was no clear evidence that PN was associated with worse cancer control, although a continued follow-up of this and other cohorts is warranted.     

Intravesical Jackson-Pratt drain for urinary diversion after augmentation cystoplasty

PURPOSE: Augmentation cystoplasty has become a primary form of bladder management in children with a noncompliant bladder. Excellent urinary drainage is required for anastomotic healing and the removal of mucous buildup. Suprapubic drainage traditionally involves a Malecot catheter, although poor irrigation and dislodgment of this type of catheter are well-known complications. We report the placement of an intravesical Jackson-Pratt drain for urinary diversion in augmented bladders. MATERIALS AND METHODS: We reviewed our use of an intravesical Jackson-Pratt drain for urinary diversion between 1995 and 1999 in 17 patients. Postoperative catheter drainage and irrigation characteristics were assessed as well as catheter related complications. RESULTS: Average patient age was 13 years (range 3 to 27). The majority of patients underwent ileal (11) or sigmoid (4) cystoplasty and 1 each underwent composite and ureteral cystoplasty. Drains remained in place an average of 27 days (range 6 to 57). All patients had excellent drainage during the postoperative period. Irrigation was subjectively easier than with a Malecot catheter. Average cost of a latex-free Malecot catheter was 2.7-fold that of a Jackson-Pratt drain. No catheters became nonfunctional before removal, although 1 was inadvertently pulled during patient transfer. CONCLUSIONS: A Jackson-Pratt drain provides excellent urinary drainage in patients undergoing augmentation cystoplasty. Multiple openings along the tube seem to improve irrigation in contrast to the single opening in a Malecot catheter, which often aspirates a region of the augmented bladder. The ready availability, decreased cost, ease of irrigation, increased pliability with decreased chance of dislodgment and lack of latex make an intravesical Jackson-Pratt drain a superior choice for augmented neurogenic bladder.     

The use of vesicostomy as permanent urinary diversion in the child with myelomeningocele.

PURPOSE: Treatment of the child with myelomeningocele presents the urologist with many challenges. While vesicostomies are usually used for temporary bladder drainage until continent reconstruction is performed, we have a population of postpubertal patients with myelomeningocele in whom vesicostomies have been preserved. We review our experience with these older children. MATERIALS AND METHODS: A search of our database of 350 patients with myelodysplasia identified 23 with urinary diversion accomplished by permanent vesicostomy. Those who had undergone vesicostomy after age 11 years were designated as group 1. Those who received a vesicostomy early in life that was maintained post puberty were designated as group 2. Indications for vesicostomy, upper tract status before and after vesicostomy, recurrent infections and complications were noted. Upper tract status was determined by serial ultrasounds during routine followup. RESULTS: Group 1 was comprised of 5 patients with mean age at vesicostomy of 17 years and a mean followup interval of 5.2 years. Group 2 was comprised of 18 patients with mean age of vesicostomy at 2.6 years and mean followup interval of 13 years. Hydronephrosis resolved in all children from both groups. Vesicostomy revision was required in 1 patient secondary to prolapse. Other complications included mild prolapse that did not require revision, stenosis requiring revision 5 months after the initial procedure and an early bilateral ureterovesical obstruction that resolved. Of the patients 33% had recurrent upper tract calculi. CONCLUSIONS: While the goal of achieving urinary continence is well worth striving for in the child with myelomeningocele, it is not realistic for all patients. We believe that permanent cutaneous vesicostomy is an acceptable alternative that the reconstructive surgeon should consider. This reliable and simple technique ensures safe decompression of the upper urinary tracts, while avoiding the complications of urinary diversion using segments of bowel.     

Isolation of the ocular surface to treat dysfunctional tear syndrome associated with computer use

Dysfunctional tear syndrome (DTS) associated with computer use is characterized by mild irritation, itching, redness, and intermittent tearing after extended staring. It frequently involves foreign body or sandy sensation, blurring of vision, and fatigue, worsening especially at the end of the day. We undertook a study to determine the effectiveness of periocular isolation using microenvironment glasses (MEGS) alone and in combination with artificial tears in alleviating the symptoms and signs of dry eye related to computer use. At the same time, we evaluated the relative ability of a battery of clinical tests for dry eye to distinguish dry eyes from normal eyes in heavy computer users. Forty adult subjects who used computers 3 hours or more per day were divided into dry eye sufferers and controls based on their scores on the Ocular Surface Disease Index (OSDI). Baseline scores were recorded and ocular surface assessments were made. On four subsequent visits, the subjects played a computer game for 30 minutes in a controlled environment, during which one of four treatment conditions were applied, in random order, to each subject: 1) no treatment, 2) artificial tears, 3) MEGS, and 4) artificial tears combined with MEGS. Immediately after each session, subjects were tested on: a subjective comfort questionnaire, tear breakup time (TBUT), fluorescein staining, lissamine green staining, and conjunctival injection. In this study, a significant correlation was found between cumulative lifetime computer use and ocular surface disorder, as measured by the standardized OSDI index. The experimental and control subjects were significantly different (P<0.05) in the meibomian gland assessment and TBUT; they were consistently different in fluorescein and lissamine green staining, but with P>0.05. Isolation of the ocular surface alone produced significant improvements in comfort scores and TBUT and a consistent trend of improvement in fluorescein staining and lissamine green staining. Isolation plus tears produced a significant improvement in lissamine green staining. The subjective comfort inventory and the TBUT test were most effective in distinguishing between the treatments used. Computer users with ocular surface complaints should have a detailed ocular surface examination and, if symptomatic, they can be effectively treated with isolation of the ocular surface, artificial tears therapy, and effective environmental manipulations.     

Consumer perceptions of health care services: implications for academic medicine.

The factor analytic development of various measures of consumer perceptions regarding characteristics of doctors and health care services is described. Index scores meeting factor analytic and reliability criteria were used to study the importance of consumer perceptions in relation to behavioral outcomes. Numerous dimensions of consumer perceptions were identified and described, including beliefs about doctor conduct in terms of quality of care and humaneness of health care delivery as well as satisfaction with such enabling components as the continuity of care, availability and convenience of services, and various access mechanisms (cost, payment mechanisms, and ease of emergency care facilities). Measures of these perceptions were shown to be related to differences in several estimates of health services utilization. The use of the index scores which have met empirical criteria is in contrast to the common practice of using individual questionnaire items as the unit of analysis in health care research. Findings are discussed in relation to program planning and evaluation in medical education, and suggestions for future research are noted.     

Adolescent chlamydia testing practices and diagnosed infections in a large managed care organization

GOAL: To determine chlamydia screening practices and the resulting positive test results for adolescents enrolled in a large nonprofit managed care organization. STUDY DESIGN: The electronic medical records of all 12- to 19-year-olds enrolled in a large nonprofit managed care organization serving a demographically diverse patient population from January 1998 through December 1999 were reviewed retrospectively. RESULTS: Among the 43,205 female and 44,133 male managed care organization members, ages 12 to 19 years in 1998-1999, 7575 adolescents (8.7%) (6914 females [16%] and 661 males [1.5%]) were tested for chlamydia. Among the members tested, chlamydia was diagnosed in 1109 adolescents (14.6%) (983 females [14.2] and 126 males [19.1%]); 761 (68.6%) adolescents were retested for chlamydia; and 182 (16.4%) had repeat positive test results. The median time to diagnosis of a repeat infection was 6 months. CONCLUSIONS: Chlamydia imposes a large disease burden in the private, organized healthcare sector. Managed care organizations can use operational data to enhance chlamydia prevention services by defining testing practices and local disease prevalence.     

Anterior cervical fractional interspace decompression for treatment of cervical radiculopathy. A review of the first 66 cases

Anterior cervical fractional interspace decompression (ACFID) is an anterior cervical partial discectomy that provides adequate neuroforaminal decompression but avoids segmental collapse and spontaneous fusion. Of 63 patients, 55 were followed from six to 49 months postoperatively (mean, 23 months). Good or excellent results were obtained in 64% of the patients and in 70% of the non-Workers' Compensation patients. Eighty-five percent of the patients and 91% of the non-Workers' Compensation patients were satisfied with the results of surgery. Eighty-seven percent of the patients returned to their original work status. An average of only 1 mm of disc space height was lost. Only two (4%) disc spaces spontaneously fused. ACFID is indicated for radiculopathy due to both soft and hard discs and can be particularly valuable in treating patients with disc herniation adjacent to a previous fusion or radiculopathy with multiple-level myelographic filling defects.     

Retroperitoneal approach to aortic surgery

The retroperitoneal approach has been recently advocated as an alternate approach to abdominal aortic surgery rather than the traditional transperitoneal approach. A comparative analysis of these two approaches was undertaken to clarify the differences. From June 1984 through June 1986, 172 patients underwent elective infrarenal abdominal aortic surgery on the Vascular Surgery Service at Eastern Virginia Medical School. One hundred nineteen were operated through a transperitoneal approach, and 53 through a retroperitoneal approach. The two groups were similar relative to age, sex, indications, risk factors and operations performed. The groups were then analyzed relative to operating time, blood transfusion, fluid replacement, ileus, morbidity, length of hospital stay, American Society of Anesthesiologists classification, and mortality. Significant differences were found: retroperitoneal patients had shorter operating time, shorter ileus, fewer cardiac complications, and shorter hospitalization than transperitoneal patients. This retrospective evaluation supports the conclusion that the retroperitoneal approach to abdominal aortic surgery is safe and beneficial in most patients. The retroperitoneal approach should therefore be given consideration in routine aortic surgery.     

Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B

Inositol hexakisphosphate kinases (IP6Ks) regulate various biological processes. IP6Ks convert IP6 to pyrophosphates such as diphosphoinositol pentakisphosphate (IP7) and bis-diphosphoinositol tetrakisphosphate (IP8). IP7 is produced in mammals by a family of inositol hexakisphosphate kinases, IP6K1, IP6K2, and IP6K3, which have distinct biological functions. The inositol hexakisphosphate kinase 2 (IP6K2) controls cellular apoptosis. To explore roles for IP6K2 in brain function, we elucidated its protein interactome in mouse brain revealing a robust association of IP6K2 with creatine kinase-B (CK-B), a key enzyme in energy homeostasis. Cerebella of IP6K2-deleted mice (IP6K2-knockout [KO]) produced less phosphocreatine and ATP and generated higher levels of reactive oxygen species and protein oxidative damage. In IP6K2-KO mice, mitochondrial dysfunction was associated with impaired expression of the cytochrome-c1 subunit of complex III of the electron transport chain. We reversed some of these effects by combined treatment with N-acetylcysteine and phosphocreatine. These findings establish a role for IP6K2–CK-B interaction in energy homeostasis associated with neuroprotection.

Inositol pyrophosphates are versatile messenger molecules that mediate a variety of cellular functions, including cell growth, apoptosis, endocytosis, and cell differentiation. The most extensively studied inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), displays a 5′-diphosphate (1, 2). IP7 is generated in mammals by a family of inositol hexakisphosphate kinases (IP6Ks) (3, 4). IP6Ks exists in three isoforms: IP6K1, IP6K2, and IP6K3. Inositol hexakisphosphate kinase-2 (IP6K2) sensitizes cells to apoptosis (5, 6). Mice with targeted deletion of IP6K2 display an increased incidence of aero-digestive tract carcinoma (7). Cell survival associated with heat shock protein 90 also involves IP6K2 (8, 9).We previously reported a major role for IP6K2 in the disposition of cerebellar granule cells as well as Purkinje cell morphology and motor coordination. The influence of IP6K2 upon cerebellar disposition involved protein 4.1N, both of which were highly expressed in cerebellar granule cells (10).To further assess the functions of IP6K2 in the brain, we explored its binding partners using coimmunoprecipitation and tandem liquid chromatography mass spectrometry (LC-MS/MS). Here, we report that IP6K2 robustly interacts with creatine kinase-B (CK-B), which regulates energy homeostasis of cells and exists in two forms, brain type (CK-B) and muscle type (CK-M). CK catalyzes the reversible transfer of the phosphate group of phosphocreatine to ADP to yield ATP (11, 12). A functional interplay between mitochondrial and cytosolic isoforms of CK regulates cellular energy homeostasis. Cytosolic CK rephosphorylates locally produced free ADP and increases creatine globally, while the mitochondrial enzyme catalyzes the conversion of creatine to phosphocreatine utilizing mitochondrial ATP (13–15).Here, we show that IP6K2 loss leads to decreased CK-B expression, reduced ATP levels, and diminished mitochondrial activity associated with increased oxidative stress. About 80 to 90% of ATP is generated in the mitochondria by oxidative phosphorylation, and diminished ATP levels are the immediate effect of mitochondrial dysfunction. Loss of IP6K2 and CK-B reflects the suppression of the mitochondrial cytochrome c1 expression, a component of complex III of the mitochondrial electron transport chain. In the present study, we report a physiologic association of CK-B and IP6K2, whose disruption impacts mitochondrial functions.Dendritic morphogenesis was reduced in IP6K2-deficient neurons and was rescued by restoring normal levels of ATP. These observations reveal an essential role of IP6K2 in the energy production of the brain. Our findings indicate that IP6K2 is a key regulator of mitochondrial homeostasis which promotes neuroprotection.