Outcome and long-term function of restorative proctocolectomy for Crohn's disease: comparison to patients with ulcerative colitis.

AIM: Restorative proctocolectomy (RPC) is the most common operation for chronic ulcerative colitis (CUC), as it provides excellent functional outcome. However, among patients with Crohn's disease (CD), RPC is generally not recommended, as outcome and long-term function may be poor. Our purpose was to compare matched cohorts of CD and CUC patients to determine whether there are differences in outcome or function. METHOD: We queried our prospectively maintained database of patients who underwent RPC from 1991 to 2008. We identified patients who underwent RPC for CD and compared them with a matched cohort of patients who underwent RPC for CUC. RESULTS: We identified 13 patients with CD (seven women, median age 34 years) and 39 patients with CUC (21 women, median age 35 years). The patients were well matched for gender, clinical and demographic variables. Seven patients (54%) with CD had proctitis, but none had perianal or ileal disease. There were four (30.8%) postoperative complications and no anastomotic leaks. The CD group experienced significantly fewer median daily bowel movements (P = 0.02), incontinence for liquids (P < 0.01) and pouchitis (P < 0.01). With a median follow up of 44 months, pouch excision rate was significantly higher in the Crohn's group (2 vs 0%, P < 0.01). CONCLUSION: In patients with CD, RPC may result in fewer daily bowel movements, less liquid incontinence and a lower incidence of pouchitis compared with CUC patients who undergo RPC. However, risk of pouch loss is higher in patients with CD. Therefore, in properly selected patients with CD, RPC provides an acceptable long-term functional outcome.

p53 nuclear protein expression is an independent prognostic marker in clinically localized prostate cancer patients undergoing radical prostatectomy.

Immunohistochemical (IHC) staining for p53 protein nuclear expression was evaluated in archival paraffin-embedded radical prostatectomy specimens from 139 patients with clinically localized prostate cancer followed up from 1 to 8 (mean, 4) years. Elevated nuclear p53 protein expression was detected in 85 (61%) of 139 patients, being heterogeneous and focal in the majority of specimens. Only four specimens displayed homogeneous nuclear accumulation of p53 protein. Disease progression, most commonly prostate-specific antigen elevation, was noted in 46 (33%) patients, with 39 (85%) having positive p53 protein IHC stains. Conversely, 93 (67%) of 139 have not recurred, with 46 (49%) having positive p53. Of all 54 p53-negative patients, 47 (87%) have had no disease recurrence. An increased p53 protein IHC stain was associated with a higher pathological stage (T1 and T2, 51% versus >/=T3, 69%) and Gleason score 2-4, 17%; 5-7, 72%; and 8-10, 87.5%). Despite these associations, p53 IHC staining was an independent predictor of disease-free survival in a multivariate analysis of p53, age, race, stage, and grade. This study revealed that a majority of clinically localized prostate cancers heterogeneously express elevated nuclear levels of p53 protein in at least a subset of malignant cells, and that this expression is an independent predictor of disease progression in prostate cancer patients after radical prostatectomy.

Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial.

Physical activity during childhood is advocated as one strategy for enhancing peak bone mass (bone mineral content [BMC]) as a means to reduce osteoporosis-related fractures. Thus, we investigated the effects of high-intensity jumping on hip and lumbar spine bone mass in children. Eighty-nine prepubescent children between the ages of 5.9 and 9.8 years were randomized into a jumping (n = 25 boys and n = 20 girls) or control group (n = 26 boys and n = 18 girls). Both groups participated in the 7-month exercise intervention during the school day three times per week. The jumping group performed 100, two-footed jumps off 61-cm boxes each session, while the control group performed nonimpact stretching exercises. BMC (g), bone area (BA; cm2), and bone mineral density (BMD; g/cm2) of the left proximal femoral neck and lumbar spine (L1-L4) were assessed by dual-energy X-ray absorptiometry (DXA; Hologic QDR/4500-A). Peak ground reaction forces were calculated across 100, two-footed jumps from a 61-cm box. In addition, anthropometric characteristics (height, weight, and body fat), physical activity, and dietary calcium intake were assessed. At baseline there were no differences between groups for anthropometric characteristics, dietary calcium intake, or bone variables. After 7 months, jumpers and controls had similar increases in height, weight, and body fat. Using repeated measures analysis of covariance (ANCOVA; covariates, initial age and bone values, and changes in height and weight) for BMC, the primary outcome variable, jumpers had significantly greater 7-month changes at the femoral neck and lumbar spine than controls (4.5% and 3.1%, respectively). In repeated measures ANCOVA of secondary outcomes (BMD and BA), BMD at the lumbar spine was significantly greater in jumpers than in controls (2.0%) and approached statistical significance at the femoral neck (1.4%; p = 0.085). For BA, jumpers had significantly greater increases at the femoral neck area than controls (2.9%) but were not different at the spine. Our data indicate that jumping at ground reaction forces of eight times body weight is a safe, effective, and simple method of improving bone mass at the hip and spine in children. This program could be easily incorporated into physical education classes.

Protein expression of p53, bcl-2, and KI-67 (MIB-1) as prognostic biomarkers in patients with surgically treated, clinically localized prostate cancer.

BACKGROUND: Protein expression in the primary tumor of the tumor suppressor gene p53 and the proto-oncogene bcl-2 have been shown to be prognostic biomarkers of cancer recurrence after radical prostatectomy in patients with clinically localized prostate cancer. Cancer cell proliferation as measured by immunohistochemical markers such as the MIB-1 antibody for Ki-67 has recently been suggested to be of prognostic value in prostate cancer. The goal of this study was to determine the clinical use of p53, Ki-67 (MIB-1), and bcl-2 immunohistochemical protein expression in the primary tumor as combined predictors of disease progression after radical prostatectomy (RP). METHODS: Protein expressions of p53, Ki-67, and bcl-2 were evaluated in archival paraffin-embedded RP specimens from 162 patients monitored from 1 to 10 years (mean, 4.5 years) and correlated to stage, grade, race, and serologic (prostate-specific antigen) recurrence after operation. RESULTS: Expression was detected in 112 (69.1%), 44 (27.2%), and 62 (38.3%) of 162 patients for p53 (1+ or greater), bcl-2 (1+ or greater), and Ki-67 (2+ or greater), respectively. Biomarker expressions were not correlated to age and race; however, all increased with increasing stage and grade. The degree of expression by percentage of malignant cells staining correlated to recurrence for p53 and Ki-67 but not for bcl-2. All three markers were correlated to raw and Kaplan-Meier recurrence by means of univariate analysis with recurrence estimates at 6 years of 60.7% versus 24.2%, 84.2% versus 38.6%, and 72.4% versus 30.6% comparing positive versus negative expression of p53, bcl-2, and Ki-67, respectively. p53 and bcl-2 remained as independent prognostic markers by Cox multivariate regression analysis. Although Ki-67 did not remain an independent marker, it added prognostic use in certain subsets of patients. CONCLUSIONS: p53, bcl-2, and Ki-67 (MIB-1) appear to be important biomarkers to predict recurrence in patients with clinically localized prostate cancer after RP, and all three biomarkers deserve further study.

Sweat gland carcinoma. Current concepts of surgical management.

In three new cases of sweat gland carcinoma that we observed within recent years, the sites were the axilla, back, and arm. Axillary lymph node dissections were performed in two of the patients and the nodes were normal. Preoperative diagnoses were hydroadenitis, squamous cell carcinoma of the skin, and pyogenic granuloma. In one patient who was followed up for four years, there has been no recurrence; the follow-up period for the other two has been short. Sweat gland carcinoma is an uncommon neoplasm that occurs mostly in the older age groups. It may be very slow growing and is extremely difficult to diagnose preoperatively. Lymph node metastases are frequent and overall survival is poor. Prognosis is related to histologic cell type and presence or absence of lymph node metastases. Treatment by wide local excision of the lesion and primary regional node dissection is recommended.

Use of the long tube in the management of patients with small-intestinal obstruction due to adhesions.

A retrospective analysis was performed of all patients admitted to our hospital over a six-year period with a diagnosis of small-intestinal obstruction due to adhesions, to assess the efficacy of treatment with long-tube decompression. Of 127 episodes of obstruction, two thirds responded to nonoperative treatment. Factors that were associated with a greater likelihood of success with long-tube decompression included incomplete obstruction, recurrent obstruction, and passage of the tube beyond the pylorus. Clinical findings were relatively reliable as diagnostic indicators of strangulation. The overall mortality was 1.5%, with no deaths due to a delay in operative intervention. A trial of long-tube decompression is recommended in patients presenting with a diagnosis of small-intestinal obstruction due to adhesions in the absence of clinical evidence of strangulation.

Hepatic subcapsular extension of pelvic lymphocele after radical retropubic prostatectomy.

Lymphoceles are a rare symptomatic complication after radical prostatectomy occurring in less than 5% of cases. We present a case of a symptomatic lymphocele that occurred after a radical retropubic prostatectomy and obturator lymphadenectomy. The lymphocele dissected along the retroperitoneum and extended into the hepatic subcapsular space and became secondarily infected with Candida albicans.

Incidence of stool guaiac conversion following extracorporeal shock wave lithotripsy.

OBJECTIVES: To study, in a prospective fashion, acute traumatic effects on the gastrointestinal tract of patients treated by extracorporeal shock wave lithotripsy (ESWL). METHODS: Stool samples from each of 54 patients were tested before and after ESWL for conversion to hemoccult positive. A minimum of one negative pre-ESWL stool guaiac test was required for inclusion into the study. A minimum of two stool guaiac tests were done after ESWL to verify negativity. Patients who converted to a positive hemoccult test after ESWL were then evaluated by colonoscopy for the source of bleeding. RESULTS: Fifty patients completed the study. A single patient (2.0%) converted to a positive post-ESWL hemoccult test and was evaluated with colonoscopy. This patient was found to have two benign adenomatous polyps in the sigmoid and descending colon after treatment for a left renal pelvis calculus. An additional patient with a slightly positive post-ESWL conversion refused further evaluation. The overall post-ESWL conversion rate to guaiac positive, therefore, was less than 4% (2 of 51 patients). CONCLUSIONS: There is no evidence of significant trauma or detectable bleeding in the normal gastrointestinal tract caused by ESWL as measured by postprocedure stool guaiac testing. Guaiac testing of the stool after ESWL may unmask pre-existing gastrointestinal disease. Therefore a positive guaiac test after ESWL warrants further evaluation. This study reaffirms that ESWL is a safe, minimally invasive technique for the treatment of urolithiasis, without significant adverse side effects on the gastrointestinal tract.

Perineal seeding of prostate cancer as the only evidence of clinical recurrence 14 years after needle biopsy and radical prostatectomy: molecular correlation.

Perineal needle tract seeding of prostate cancer is an unusual complication of perineal prostate biopsy. We report a case with the longest known interval from biopsy to perineal recurrence--14 years. The prostate-specific antigen did not become detectable until 12 years after biopsy and no other metastases were apparent, suggesting that the patient's perineal disease was an isolated recurrence. Immunohistochemical staining of the perineal recurrence and the original biopsy and prostate for the p53 tumor suppressor gene and bcl-2 oncogene proteins revealed rare/absent p53 expression but marked increased bcl-2 expression. This unusual molecular pedigree may help to explain this rare clinical scenario.

Three-dimensional computer-simulated prostate models: lateral prostate biopsies increase the detection rate of prostate cancer.

OBJECTIVES: Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We developed a novel three-dimensional (3D) computer-assisted prostate biopsy simulator based on whole-mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. METHODS: We obtained digital images of 201 step-sectioned whole-mounted radical prostatectomy specimens. 3D computer simulation software was developed to accurately depict the anatomy of the prostate and all individual tumor foci. Additional peripheral devices were incorporated into the system to perform interactive prostate biopsies. We obtained 18 biopsies of each prostate model to determine the detection rates of various biopsy protocols. RESULTS: The 10- and 12-pattern biopsy protocols had a 99.0% detection rate; the traditional sextant biopsy protocol rate was only 72.6%. The 5-region biopsy protocol had a 90.5% detection rate and the 14-pattern, which includes all the biopsies used in the patterns above, only added 1 additional positive case (99.5%). Transitional zone and seminal vesicle biopsies did not result in a significantly increased detection rate when added to the patterns above. Only one positive model was obtained when the transitional zone biopsies were added. The lateral sextant pattern had a detection rate of 95.5%, and the 4-pattern lateral biopsy protocol had a 93.5% detection rate. CONCLUSIONS: Our results suggest that all the biopsy protocols that use laterally placed biopsies based on the 5-region anatomic model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.

Laparoscopy for the acute abdomen in the postoperative urologic patient.

OBJECTIVES: Exploratory laparotomy offers the greatest diagnostic accuracy of intra-abdominal pathologic processes, but can be associated with significant morbidity. Laparoscopy provides diagnostic capabilities equivalent to that of open exploration, but with potentially less morbidity. We present 3 cases in which laparoscopy was used to diagnose and manage urologic patients with an acute abdomen in a postoperative period. METHODS: Three patients underwent laparoscopy between 1 and 14 days postoperatively for an acute abdomen (fever, elevated white blood cell count, and peritoneal signs). The initial procedures included a pubovaginal sling repair with fascia lata, endoscopic placement of a percutaneous gastrostomy tube, and a laparoscopic ureterolithotomy for a distal stone. RESULTS: In each of the 3 patients laparoscopy revealed misplacement or malfunction of a previously placed tube. In all cases, the patient was managed laparoscopically without the need for laparotomy. CONCLUSIONS: These cases demonstrate the feasibility of laparoscopy to provide diagnostic and therapeutic solutions to postoperative urologic patients presenting with an acute abdomen.

Significance of familial history of prostate cancer to traditional prognostic variables, genetic biomarkers, and recurrence after radical prostatectomy.

OBJECTIVES: Prostate cancer (PCa) has a familial predisposition imparting an increased risk of developing the disease in those with a family history. The pathologic characteristics are similar to sporadic cases; however, the disease-free survival rates of hereditary PCa have recently been disputed, with one major study suggesting that familial cases have higher recurrence rates. Our study seeks to support or refute this association and to evaluate the genetic biomarkers p53, bcl-2, Ki-67, and neovascularity between familial and sporadic disease. METHODS: We retrospectively reviewed data of 573 patients who underwent radical prostatectomy over an 11-year period. Of these, 474 patients had known family history data. Univariable statistical analysis using the Pearson chi-square test and Kaplan-Meier disease-free survival analysis was performed to identify any correlation between the tested variables and family history. Smaller subsets of this cohort that had available archival material for immunohistochemical staining and family history data were analyzed in a similar manner. RESULTS: The preoperative variables (prostate-specific antigen, prostatic acid phosphatase, clinical stage, highest biopsy Gleason sum, and glandular differentiation) and postoperative variables (stage, highest Gleason sum, and glandular differentiation) did not correlate with family history. Kaplan-Meier disease-free survival analysis revealed no differences between sporadic and familial cases. The analysis of p53, bcl-2, Ki-67, and angiogenesis revealed that only increasing p53 expression and positive family history of PCa approached significance (P = 0.057). CONCLUSIONS: Prognostic variables routinely used in PCa and selected genetic biomarker immunostaining abnormalities are not significantly different in men with and without a family history of PCa. Disease-free survival after radical prostatectomy is also unaffected by family history.

Prostate-specific antigen to predict outcome of external beam radiation for prostate cancer: Walter Reed Army Medical Center experience, 1988-1995.

OBJECTIVES: To assess the ability of pretreatment and post-treatment prostate-specific antigen (PSA) measurements, clinical tumor stage, tumor grade, Gleason sum, race, age, and radiation dose to predict the recurrence of prostate cancer following external beam radiation therapy (XRT) since the introduction of PSA as a tumor marker at one tertiary care center. METHODS: The recurrence of prostate cancer among 371 evaluable patients of 389 patients treated with XRT at Walter Reed Army Medical Center was analyzed using Kaplan-Meier survival methodology and Cox multivariable regression models. Serologic (PSA) recurrence was determined using three consecutive rises in PSA after a nadir value. Clinical recurrence was defined as local recurrence (palpable or positive biopsy) and/or distant (radiographically evident) recurrence. Mean and median follow-up is 40.2 and 39.4 months, respectively (range 3.0 to 89.5), and minimum follow-up is 18 months for patients who were alive at the time of analysis. No patient received adjuvant hormonal therapy. Potential prognostic factors evaluated are pretreatment PSA, PSA nadir, age, race, clinical tumor stage, tumor grade, Gleason sum, and radiation dose. RESULTS: Of the 371 evaluable patients, 125 had disease recurrence. The Kaplan-Meier 5-year disease-free survival (DFS) rates for significant pretreatment variables in univariate analyses are as follows: pretreatment PSA less than 4 (79%), 4.1 to 10 (67%), 10.1 to 20 (57%), 20.1 to 50 (27%), and more than 50 (0%); for clinical tumor Stage T1a-T1c (84%), T2a-T2c (51 %), and T3-T4 (29%); for tumor grade well (58%), moderate (58%), and poor (30%). Four-year DFS rates for Gleason sum are 2 to 4 (82%), 5 (72%), 6 (56%), and 7 to 10 (48%). In multivariable Cox regression analysis with backward elimination of nonsignificant variables, age, race, tumor grade, and radiation dose were eliminated, leaving pretreatment PSA, clinical tumor stage, and Gleason sum as significant prognostic factors. Analysis of a Cox model that included nadir PSA as a time-dependent variable showed it to be the strongest prognostic factor variable in the analysis. CONCLUSIONS: XRT remains a suitable treatment modality for patients with pretreatment PSA less than 20.0, clinical tumor Stages T1-T2, and Gleason sum 2 to 6 prostate cancer. Patients achieving a nadir value less than 0.5 have more durable treatment outcomes.

Primary hormonal therapy for prostate cancer: experience with 135 consecutive PSA-ERA patients from a tertiary care military medical center.

The use of prostate specific antigen (PSA) in the 1990s has brought on a stage migration of prostate cancer. Despite that, many men have still presented with metastatic prostate cancer in the past decade. The use of primary hormone therapy in the PSA era at a tertiary care Army Medical Center is studied in this paper. Charts were reviewed of 135 men who were diagnosed with metastatic prostate cancer and treated with hormone therapy as a primary treatment between 1989 and 1995. Statistical analysis was used to determine significant predictor variables on the time to disease progression. In univariate analysis clinical stage, pretreatment alkaline phosphatase and nadir PSA values were significant predictors of time to progression. Race and type of treatment were not. In multivariate analysis the relative risk of progression was 3.2 for patients with an alkaline phosphatase >252 and 16.5 for patients with a nadir >2.0. This study supports the argument that racial disparities in prostate cancer outcomes are due to access to care. Furthermore, the survival rate for patients with D-2 disease is better than in the pre PSA studies. Clinical stage, pretreatment alkaline phosphatase and PSA nadir can be used to predict response for those men presenting with metastatic prostate cancer.

Investigating the distribution of prostate cancer using three-dimensional computer simulation.

The objective of this work was to investigate the distribution of prostate cancer using three-dimensional (3-D) computer simulation. Two hundred and eighty-one 3-D computer prostate models were constructed from radical prostatectomy specimens. An algorithm was developed which divided each model into 24 symmetrical regions, and it then detected the presence of tumor within an individual region. The distribution rate of prostate cancer was assessed within each region of all 281 prostate models, and the difference between the rates was statistically analyzed using Mantel-Haenszel methodology. There was a statistically significant higher distribution rate of cancer in the posterior half (57.2%) compared to the anterior half ( 40.5%; P=0.001). The base regions (36.8%) had a statistically significant lower distribution rate than either the mid regions (56.3%; P=0.001) or the apical regions (53.5%; P=0.001). The mid regions did have a statistically significant higher distribution rate compared to the apical regions (P=0.032). There was no statistically significant difference between the distribution rate on the left half (48.5%) compared to that on the right half (49.2%; P=0.494). The spatial distribution of prostate cancer can be analyzed using 3-D computer prostate models. The results illustrate that prostate cancer is least commonly located in the anterior half and base regions of the prostate. Through an analysis of the spatial distribution of prostate cancer, we believe that new optimal biopsy strategies and techniques can be developed.

Checklist self-evaluation in a standardized patient exercise.

BACKGROUND: Standardized patient (SP) exercises are expensive and time consuming. We hypothesized that self-evaluation would further the goals of teaching and evaluation for a group of medical students. METHODS: Students were given self-evaluation checklists (essentially identical to those filled out by the SPs) and completed them prior to reviewing the SP checklists. Agreement between student and SP checklists (whether each item was checked or not) and the extent of agreement on the interactional skills rating scales were assessed. RESULTS: Overall agreement was 93%, with 98% agreement on interactional items, 92% on physical examination items, and 89% on history items. Disagreements tended to be clustered on a few items in each scale. Scores on the interactional skills rating scales also showed strong agreement. CONCLUSION: The use of checklists and rating scales in this context is well established. At virtually no cost, a self-evaluation tool adds a valuable dimension to the exercise.

Does clinical exposure affect medical student examination performance?

BACKGROUND: Traditionally important components of the surgical clerkship curriculum include lectures, small-group sessions, readings, clinical exposure, and testing. Time constraints require compromise among all these elements. At our institution, clinical exposure of medical students varies according to their team assignments. They differ primarily in exposure to such topics as trauma, inflammatory bowel disease (IBD), and vascular surgery. PURPOSE: The goal of this study was to quantify the influence of clinical exposure on medical student education, testing whether it influences examination performance. METHODS: At the beginning of the clerkship, students were given a written multiple-choice examination covering these three topics. They completed two 4-week blocks on surgery services in various settings. At the end of the clerkship, they were reexamined. Differences between pretest and posttest overall mean rank were analyzed using the Wilcoxon signed ranks test. Differences in improvement based on clinical exposure were analyzed using the Mann-Whitney U test. RESULTS: Statistically significant improvement was seen in overall examination performance, as well as in each of the subsections. However, these improvements could not be accounted for by clinical exposure. There was no statistically significant difference in mean rank in improvement based on clinical exposure to vascular, IBD, or trauma. CONCLUSIONS: Student examination scores improved over the course of the clerkship. No improvement could be attributed to greater clinical exposure to a topic.

Proctectomy for inflammatory bowel disease.

Between July 1973 and October 1984, we performed proctectomy either as part of a primary proctocolectomy or as a secondary staged procedure in 388 patients with ulcerative colitis and in 39 patients with Crohn's disease. The proctectomies were performed using a two-team synchronous approach. An intersphincteric or perimuscular technique was employed. All perineal wounds were closed and drained by suction drainage and the pelvic peritoneum was closed in all cases. Two patients died in the early postoperative period, one from a pulmonary embolus and one from sepsis. Three patients had to be reexplored for postoperative hemorrhage, in all cases from a branch of the superior hemorrhoidal artery. Postoperative perineal hematoma developed in two patients and perineal abscess developed in four patients which necessitated opening of the perineal skin wound. Nonhealing of the perineal wound occurred in 3 of 388 patients with ulcerative colitis and in 5 of 39 patients with Crohn's disease. No perineal dehiscence or hernias were seen. Postoperatively, one man was permanently impotent and two had prolonged but temporary impotence. Three patients had retrograde ejaculation at last follow-up.

A continent colostomy: The magnetic stoma cap.

An apparatus to create continence in an end left-sided colostomy in dogs is assessed. The device consists of a samarium-cobalt magnetic ring encased in methyl methacrylate and a magnetic cap. The ring is implanted in the abdominal wall and the colon delivered through it and matured to the skin. The stoma is later obturated by the magnetic cap to provide continence. Ten dogs exposed to "uncoated" samarium-cobalt magnets for periods of up to eight months showed no elevation of cobalt levels in the serum or tissues and no histopathologic changes on postmortem examination. In twelve dogs, magnetic rings were used to create continent colostomies. Eleven of twelve dogs followed for periods up to eight months were continent and tolerated the appliance well. One ring was extruded after a peristomal skin dehiscence occurred. Two skin strictures appeared and were readily controlled by digital dilatation. Sinus, fistula, or infection were not seen. Clinical application of this device is discussed.