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Planned staged reoperative necrosectomy using an abdominal zipper in the treatment of necrotizing pancreatitis.

PURPOSE: The optimal operative treatment for severe necrotizing pancreatitis (SNP) still remains controversial. This article describes the operative approach with a planned staged necrosectomy using the "zipper" technique. METHODS: Between 1996 and 2000, 35 patients with SNP were treated with this approach. The patient demographics, etiology and severity of SNP, hospital course, and outcome were recorded and comparisons of several parameters were made between the patients who survived and those who died. RESULTS: Hospital mortality was 34%. A total of 16 fistulae developed in 11 patients (31%), recurrent intra-abdominal abscesses in 4 (11%), and hemorrhaging in 5 (14%). The patients who died compared with those who survived had a higher Acute Physiology and Chronic Health Evaluation (APACHE)-II score on admission (14.5 vs 9, P < 0.001), extrapancreatic extension of necrosis more often (100% vs 65%, P = 0.02), and developed postoperative hemorrhaging more often (33% vs 4%, P = 0.038). A multivariate logistic analysis revealed an APACHE-II score of > 13 on admission (P = 0.018) and an extension of necrosis behind both paracolic gutters (P < 0.001) to both be prognostic factors for mortality. CONCLUSIONS: Severe necrotizing pancreatitis still carries significant morbidity and mortality. This surgical approach facilitates the removal of all devitalized tissue and seems to decrease the incidence of recurrent intra-abdominal infection requiring reoperation. An APACHE-II score of > or = 13 and an extension of necrosis behind both paracolic gutters was thus found to signify a worse outcome.

APACHE↗

Recurrent hepatitis C after retransplantation: factors affecting graft and patient outcome.

Retransplantation (re-LT) of patients with recurrent hepatitis C virus (HCV) carries significant morbidity and mortality, negatively impacting on an already scarce donor allograft pool. In this study, we investigated the outcome of allografts and patients after re-LT due to recurrent HCV. Between 1989 and 2002, 47 patients were retransplanted at our institution due to HCV-related graft failure. Clinical HCV recurrence after re-LT was diagnosed when patients had acute liver enzyme elevation correlated with histological recurrence. The independent influence of these variables on survival was tested using Cox regression model. Chi-squared tests were used to examine the influence of individual demographic and pre/perioperative variables on recurrence. Thirty-one (66%) patients died after re-LT (median 2.2 months). Donor age >60, clinical HCV recurrence, and graft failure due to cirrhosis were significant risk factors for mortality (risk ratios of 3.6, 3.3, and 2.4, respectively). Pre-LT MELD score was lower among survivors (22+/- 5 vs. 27+/- 8). Following re-LT, 38 patients had at least one biopsy due to acute liver dysfunction; 19 of them (50%) had recurrence within the first 3 months. High-dose solumedrol was correlated with early recurrence. No association was found between time of recurrence after the first LT and time of recurrence after re-LT. In conclusion, patients with cirrhosis due to recurrent HCV undergoing re-LT have an extremely high mortality rate; older allografts should be avoided in retransplanting these patients. The timing of clinical recurrence after initial liver transplantation is not predictive of the timing of recurrence after re-LT. Patients experiencing early graft failure due to accelerated forms of HCV should not be denied re-LT with the expectation that a similar disease course will occur after re-LT.

Adult↗

Prevention of sinus tympani retraction following tympanoplasty. How I do it.

Tympanoplasty for sinus tympani retraction may result in delayed recurrence of the original problem. This is especially true in children with marginal eustachian tube function. Autogenous tragal cartilage, scored on one surface with perichondrium attached on the other, produces a "natural bend" in the cartilage. When placed in the middle ear, with the scored convex surface facing the promontory, retraction into the sinus tympani can be prevented. This simple, yet effective, surgical technique is outlined.

Adult↗

Effect of penicillin or penicillin and dexamethasone in cattle with infectious bovine keratoconjunctivitis.

To evaluate the efficacy of penicillin or penicillin and dexamethasone for treatment of infectious bovine keratoconjunctivitis, 6- to 8-month-old beef heifers with clinical signs of infectious bovine keratoconjunctivitis were randomly assigned to 1 of 3 treatment groups: penicillin only, penicillin and dexamethasone, or control. Cattle assigned to the penicillin group (n = 18) were treated with 3 daily subconjunctival injections of procaine penicillin G. Cattle assigned to the penicillin/dexamethasone group (n = 13) were treated with 3 daily subconjunctival injections of procaine penicillin G and dexamethasone sodium phosphate. Control cattle (n = 14) were not treated. Healing times and frequency of recurrence for corneal ulcers; severity, diameter, and surface area measurements of corneal ulcers; and clinical scores did not differ among the 3 groups. Frequency of Moraxella bovis isolation from specimens of ocular secretions from ulcerated and non-ulcerated eyes was similar in all groups. Minimum inhibitory concentration of penicillin G for 95 of the 102 tested M bovis isolates was 0.3 U/ml, and for 7 others was 0.03 U/ml. When first and last specimens from 42 of 45 calves with isolation of M bovis on serial microbial cultures were compared, the susceptibility of each last isolate was similar to that of the corresponding first isolate.

Animals↗

Narrow-band ultraviolet B (ATL-01) phototherapy is an effective and safe treatment option for patients with severe seborrhoeic dermatitis.

BACKGROUND: Seborrhoeic dermatitis is a common papulosquamous dermatosis affecting 2-10% of the adult population. Current treatment options are limited and not always satisfactory. Objectives We aimed to investigate the efficacy of narrow-band ultraviolet (UV) B (TL-01) phototherapy as an alternative treatment for seborrhoeic dermatitis. METHODS: Eighteen patients with severe disease were enrolled in an open prospective study. Treatment was given three times weekly until complete clearing or to a maximum of 8 weeks. A clinical score assessing erythema, scaling, infiltration and pruritus was performed at baseline and every 2 weeks thereafter. Additionally, the patients were asked to rate the intensity of pruritus on a visual analogue scale. After completion of the study the patients were followed up to determine the median time interval until recurrence. RESULTS: All patients responded favourably to treatment, with six showing complete clearance and 12 marked improvement. The median clinical score decreased from 7.5 (range 4-8) at baseline to 0.5 (range 0-3) after 8 weeks of treatment (P = 0.005). The median pruritus score decreased from 4.5 (range 0-8) at baseline to 0 (range 0-3) at week 8 (P = 0.008). Relapses occurred in all patients after a median of 21 days (range 12-40). No side-effects of treatment were observed except occasional episodes of a moderate erythemal response. CONCLUSIONS: Narrow-band UVB phototherapy appears to be a very effective and safe treatment option for patients with severe seborrhoeic dermatitis.

Adolescent↗

[Laparoscopic incisional hernia repair: prospective non randomized trial in 51 cases].

AIM OF THE STUDY: Insertion of a mesh in treatment of incisional hernias reduces the risk of recurrence. A single prospective randomized trial have compared laparoscopic and open approach: there were less postoperative complications and fewer recurrences in the laparoscopic group. Aim of this prospective trial was to control these results. PATIENTS AND METHODS: From January 2000 to May 2005, 51 consecutive incisional hernias were operated on by a laparoscopic approach. Incisional hernia was single in 41 and double in 5. It was median in 41 and lateral in 10. Previous hernia repair was noticed in 33.3%. Main criteria was recurrence. We have considered whether one of the following criteria was associated with the risk of recurrence: sex, obesity, previous repair, pre and preoperative sizes of the hernia, uni or multi orificial aspect of the hernia, median or lateral location, mesh size, ratio mesh surface/hernia surface. Others were postoperative mortality and morbidity, duration of hospitalisation and occurrence of late events. RESULTS: At 2 years all patients were followed. Follow up achieved 3 years in 23 cases and 4 years in 9. Recurrence was observed in 7 (13.7%). None predictive factor was disclosed. No death occurred. Median postoperative pain score at D1, D2 and D3 was respectively 3.1+/-1.9, 2.9+/-2.3 and 2.3+/-2.1. Mean postoperative stay was 4.1+/-1.9 days. Seven postoperative complications occurred, al benign. During follow-up 18 events were noticed and of these 8 were chronic abdominal pain. CONCLUSION: This technique could be employed for every type of incisional hernia but peristomial hernias (not assessed in this study) and every patient. Technical improvements ought to be find to reduce recurrence rate.

Aged↗

Effect of neurological dysfunction on health-related quality of life in patients with high-grade glioma.

The purpose of the study was to assess health-related quality of life (HQL) in patients with high-grade malignant glioma of the brain. The EORTC core Quality of Life Questionnaire (QLQ-C30) and a Brain Cancer Module (BCM20) were administered at baseline and several weeks later (follow-up) to 105 patients with either recently-diagnosed (n = 41) or recurrent (n = 64) malignant glioma. In addition, the attending neurologists completed a standard neurological examination, a modified Barthel Activities of Daily Living Index (BADLI) and the Karnofsky Performance Scale (KPS). In a preliminary step, the QLQ-C30 was found to have acceptable reliability (internal consistency and test-retest reliability). Newly-diagnosed patients and those with a KPS of 80-100 had significantly better physical, role and cognitive functioning and global quality of life with less fatigue, visual disorder, motor dysfunction, communication deficit, weakness of both legs and trouble controlling the bladder than did those with recurrent disease and those with a KPS of 50-70. Similarly, those capable of independent activities of daily living, as reported on the BADLI, had higher functioning scores and less fatigue than did those who were not independent. Patients with dysphasia, mental confusion or motor deficit on neurological examination reported significantly lower levels of physical, role, cognitive, emotional and social functioning and global quality of life than did patients not having these difficulties. They also had significantly more symptoms. In patients with deteriorating neurological status between baseline and follow-up, there was a marked decline in cognitive, physical, role, emotional and social functioning and global quality of life and an increase in fatigue. Thus, there are significant differences in HQL between patients with newly-diagnosed and recurrent brain cancer and between patients with differing KPS and BADLI scores. In addition, the HQL scores provide details not provided by the KPS and the BADLI. Deterioration in neurological function is accompanied by significant deterioration in a range of HQL domains and in global quality of life.

Adolescent↗

[Role of endoanal ultrasound in the evaluation of fistula-in-ano treated with a seton].

AIM: The aim of this study was to define the role of endorectal ultrasound in the evaluation of transphincteric fistula-in-ano treated with a seton. METHODS: Fifty-one patients affected by complex fistula-in-ano and treated with the application of a drain seton at the Second Unit of General Surgery of the University of Cagliari were recruited for the study. Clinical and ultrasonographic (US) evaluation, with transanal scans, were performed in each case before operation. Intraoperative demonstration of a transphincteric track was an indication for a partial fistulotomy with the application of a seton, tied up loosely around the external sphincter. If clinical and US evaluation, during follow-up, revealed a good drainage of the fistula by the seton and its superficialization, definitive fistulotomy was performed. RESULTS: Endoanal US had an 88.2% accuracy. Sclerosis around the seton was observed in 9 patients (17.6%); in other 9 cases a surgical toilette of the track was necessary because of the bad drainage carried out by the seton. Definitive fistulotomy was performed in 35 patients, whilst 16 are still bearer of the seton. After a mean follow-up of 39.5 months, 1 recurrence (2.9%) has occurred. Functional results were satisfactory: 55.9% of the patients has a perfect continence and 88.2% has a Wexner's incontinence score of up to 5. CONCLUSIONS: At skilled institutions, endoanal ultrasound allows to optimize the therapy of transphincteric fistula-in-ano treated with a seton and contribute to obtain good results in terms of recurrence and functional outcomes.

Adolescent↗

Revisiting the open Bankart experience: a four- to nine-year follow-up.

BACKGROUND: The open Bankart technique for posttraumatic recurrent anterior instability has become the procedure of choice for patients who do not respond to nonoperative treatment. HYPOTHESIS: The open Bankart procedure renders stable and well-functioning shoulders in the long term in a large proportion of patients. STUDY DESIGN: Retrospective follow-up study with independent reexaminers. METHODS: Fifty-four patients (54 shoulders) with symptomatic, posttraumatic, recurrent anterior shoulder instability underwent an open Bankart reconstruction procedure with suture anchors. All of the patients had a Bankart lesion. Forty-seven patients (87%) were reexamined by independent observers at a mean follow-up period of 69 months (range, 48 to 114). RESULTS: The recurrence rate, including both dislocations and subluxations, was 17% (8 of 47). The median Rowe score was 90 points (range, 24 to 100) at the follow-up, and the median Constant score was 88.5 points (range, 41 to 100). External rotation in abduction was a median of 90 degrees (range, 25 degrees to 125 degrees ) in the involved shoulders, as compared with 97.5 degrees (80 degrees to 125 degrees ) in the noninjured shoulders (P < 0.0001). CONCLUSIONS: We conclude that, in the long term, the open Bankart procedure resulted in an unexpectedly high number of patients with failure in terms of stability. These results emphasize the importance of performing long-term follow-up studies after surgical reconstruction for unidirectional, posttraumatic, anterior shoulder instability using any type of technique.

Adolescent↗

Quality of life after tension-free vaginal tape surgery for female stress incontinence.

OBJECTIVE: To undertake a long-term follow-up evaluation of the quality of life (QOL) of women who had undergone a tension-free vaginal tape (TVT) procedure. MATERIAL AND METHODS: During the period 1995-2001, 970 women with urinary stress incontinence underwent TVT surgery at the Department of Obstetrics and Gynecology, Falun Hospital. A questionnaire was mailed on average 5.7 years after the TVT procedure. Two incontinence-specific QOL instruments--the Incontinence Impact Questionnaire-7 (IIQ-7) and the Urogenital Distress Inventory-6 (UDI-6)--were administered. An additional questionnaire included general questions and questions about chronic diseases that may be associated with urinary incontinence. RESULTS: The mean age at surgery was 58.7 years (range 29-89 years). Of 913 eligible women, 768 (78.9%) responded. Mean IIQ-7 and IDU-6 scores as estimated by the women improved dramatically at follow-up as compared to preoperative values: from 43.7 to 11.5 for the IIQ-7 and from 54.2 to 24.0 for the UDI-6 on a scale from 0 to 100 (p = 0.0001 for both). There were few differences in mean QOL scores even 8 years after TVT surgery, compared to those determined a shorter time after the operation. Women with diabetes, chronic constipation, chronic bronchitis and preoperative recurrent urinary infections had a relative improvement in QOL of the same magnitude as that of the remaining study population. Advanced age was negatively associated with an improvement in QOL scores. CONCLUSIONS: Improvements in measures of QOL after TVT surgery are dramatic and persist for years. Women with concomitant diseases that may be associated with urinary incontinence can be assured that there is a good chance of success with TVT surgery.

Adult↗

[Palliative treatment of esophageal cancer with dysphagia: more favourable outcome from single-dose internal brachytherapy than from the placement of a self-expanding stent; a multicenter randomised study].

OBJECTIVE: To compare the results of single-dose internal irradiation (brachytherapy) and self-expanding metal stent placement in the palliation of oesophageal obstruction due to cancer of the oesophagus. DESIGN: Randomised trial. METHOD: In the period from December 1999-Jun 2002, 209 patients with dysphagia due to inoperable carcinoma of the oesophagus were randomised to placement of an Ultraflex stent (n = 108) or single-dose (12 Gy) brachytherapy (n = 101). Primary outcome was relief of dysphagia; secondary outcomes were complications, persistent or recurrent dysphagia, health-related quality of life, and costs. Patients were followed up by monthly home visits from a specialised nurse. RESULTS: Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. Stent placement resulted in more complications than did brachytherapy (36/108 (33%) versus 21/101 (21%); p = 0.02), due mainly to an increased incidence of late haemorrhage in the stent group (14 versus 5; p = 0.05). The groups did not differ with regard to the incidence of persistent or recurrent dysphagia or median survival (p > 0.20). In the long term, quality-of-life scores were higher in the brachytherapy group. Total medical costs were also similar for both treatments: Euro 8,215 for stent placement and Euro 8,135 for brachytherapy. CONCLUSION: Brachytherapy provided better long-term relief of dysphagia than did stent placement and also produced fewer complications. Brachytherapy is therefore recommended as the preferred treatment for the palliation of dysphagia due to oesophageal cancer.

Aged↗

Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group.

PURPOSES: A randomized trial was conducted to compare tumorectomy and breast irradiation with modified radical mastectomy. We have analyzed the patterns of failure in each arm of the trial and the prognostic factors that have an independent effect on treatment failures and overall survival. PATIENTS AND METHODS: The trial included 179 patients with breast cancer of up to 20 mm in diameter at macroscopic examination. Eighty-eight patients had conservative management and 91 a mastectomy. All patients had axillary dissection with frozen-section examination. For patients with positive axillary nodes (N+), a second randomization was performed: lymph node irradiation versus no further regional treatment. Patterns of failure were determined by a competing-risk approach and multivariate analysis. A prognostic-score was determined by multivariate analysis. RESULTS: Overall survival, distant metastasis, contralateral breast cancer, new primary malignancy, and locoregional recurrence rates were not significantly different between the two surgical groups, or between lymph node irradiation groups. Most recurrences appeared during the first 10 years. Three distinct prognostic groups were determined taking into account age, tumor size, histologic grading, and number of positive axillary nodes. CONCLUSION: Long-term results support conservative treatment with limited surgery and systematic breast irradiation as a safe procedure for the management of small breast cancers. Four easily obtainable clinical and histologic factors may be combined in a prognostic score that is highly predictive of overall and event-free survival.

Adult↗

Chronic stimulation of the globus pallidus internus for control of primary generalized dystonia.

Our experience of deep brain stimulation of the globus pallidus internus (GPi-DBS) for dystonia is summarized. A total of 5 patients with primary generalized dystonia underwent GPi-DBS. There were 3 males and 2 females. The age at onset of dystonia ranged from 8 to 45 years and the age at surgery for GPi-DBS ranged from 17 to 59 years. Two of the patients had been treated previously by bilateral thalamotomy or unilateral pallidotomy at other clinics and then developed new symptoms or recurrence. All were stimulated bilaterally. No surgical complications were encountered. The symptoms of dystonia were scored by the Burke-Fahn-Marsden dystonia rating scale (BFMDRS). The scores ranged from 18 to 62 before surgery. An improvement in the symptoms of dystonia was observed soon after the initiation of GPi-DBS, and additional progressive improvement was noted during a period of months or even years after surgery. The score at 6 months after surgery reached a level ranging from 4 to 23. The improvement in score ranged from -51% to -92%. GPi-DBS produced a marked effect even in patients who had previously undergone thalamotomy or pallidotomy. At 6 months after surgery, all patients were receiving bipolar stimulation with a wide interpolar distance, using contact 0 or 1 as the cathode and contact 2 or 3 as the anode. Stimulation was being performed at an intensity of around 2.0 V with a pulse width of 0.21 ms at a high frequency ranging from 120 to 140 Hz. GPi-DBS represents an important therapeutic option in many patients with primary generalized dystonia.

Adolescent↗

[National project for the management of clinical processes. Surgical treatment of inguinal hernia].

INTRODUCTION: The high prevalence of surgical treatment for inguinal hernia (especially in general surgery) prompted the Spanish Association of Surgeons to perform a national study to identify the most important indicators. OBJECTIVE: To analyze healthcare quality in elective surgery for inguinal hernia by evaluating scientific-technical quality, efficiency, effectiveness, and patient satisfaction. MATERIAL AND METHODS: A prospective, longitudinal, descriptive study from diagnosis to postoperative follow-up was performed. Patients who underwent surgery for unilateral or bilateral, primary or recurrent inguinal hernias were included. Exclusion criteria were emergency surgery and associated surgical procedures. Clinical indicators were selected after a literature review. RESULTS: Forty-six hospitals corresponding to 16 Autonomous Communities with a total of 386 patients participated in this study. The mean follow-up was 18 months. The mean age of the patients was 56.33 years and 88.3% were male. Half the patients (50.1%) were American Society of Anesthesiologists (ASA) grade I. A total of 95.6% did not comply with the protocol for preoperative tests of the Spanish Association of Surgeons. Antibiotic prophylaxis was used in 75.39% and thromboembolic prophylaxis was used in 40.04%. Ambulatory surgery was performed in 33.6%. Local anesthesia and sedation only were used in 16.36% of the patients. The most frequently used surgical procedures involved mesh repair (Lichtenstein 50%, Rutkow-Robbins 17.1%), laparoscopy was used in 5.2% of the patients, and the Shouldice technique was used in 8.5%. The mean length of hospital stay was 47.5 hours in inpatients and was 11.65 hours in patients who underwent ambulatory surgery. Notable among the complications was hematoma in 11.6%. Ninety-six percent of the patients were satisfied or highly satisfied. The most highly scored items in the satisfaction survey were those related to information, personal dealings with staff, and the staffs kindness. The lowest scored items dealt with punctuality and accessibility. Follow-up at 18 months showed a recurrence rate of 4.11% with a total recovery time estimated by patients of 7.26 weeks. CONCLUSIONS: Analysis of the process revealed areas for improvement and strong points. Strong points consisted of up-to-date choice of surgical technique. The most frequently used techniques were tension-free procedures and the Shouldice technique. The following areas for improvement were identified: adherence to protocols for preoperative evaluation, increased use of ambulatory surgery, local anesthesia and sedation, appropriate use of antibiotic and thromboembolic prophylaxis in selected patients and a reduction in the length of hospital stay in inpatients. Patient satisfaction with the treatment was acceptable.

Adult↗

Relapse prevention with gepirone ER in outpatients with major depression.

To evaluate long-term efficacy and tolerability of the serotonin 5-HT1A receptor agonist, gepirone extended release (ER), a multicenter, randomized, placebo-controlled relapse prevention study was performed in patients with recurrent major depression (DSM-IV criteria). Patients 18 to 70 years, with a primary diagnosis of recurrent major depression (DSM-IV; 296.3) and a screening and baseline HAMD-17 total score >/=20 were eligible. After a 3- to 14-day (dependent on pretrial medication) single-blind placebo washout period, eligible patients entered an 8- or 12-week (depending on time to remission) open-label gepirone ER treatment period. They initially received a dose of 20 mg/d gepirone ER and were titrated to a dose of 40 to 80 mg/d. Patients who achieved remission (HAMD-17 total score </=8) were randomized to double-blind continuation of their gepirone ER treatment or placebo for 40 to 44 weeks. The primary end point was a comparison of the relapse rates between gepirone ER and placebo. Relapse was defined as a HAMD-17 total score >/=16 or discontinuation for lack of efficacy. A total of 420 patients were treated in the open-label phase. Of these, 303 (72.1%) completed the open-label phase and 250 (59.5%) fulfilled the criteria for remission and were randomized into the double-blind continuation phase (gepirone ER: n = 126; placebo: n = 124). The mean (+/-SD) final titrated dose of gepirone ER was 61.9 (+/-17.0) mg/d in the double-blind continuation phase. The relapse rate in the gepirone ER group was statistically significantly lower than that in the placebo group, 23.0% versus 34.7%, respectively (P = 0.024). During the open-label phase, adverse events that occurred in more than 5% of patients were nausea (15.7%), dizziness (13.1%), headache (12.9%), insomnia (6.2%), and vertigo (6.0%). During the continuation phase, the incidence of newly or re-emerging adverse events was similar with gepirone ER (43.7%) and placebo (42.7%). Adverse events different from those occurring during the open-label phase were not apparent. All adverse events occurred in less than 5% of patients with the exception of flu syndrome and headache. In conclusion, gepirone ER at a dose range of 40 to 80 mg/d is effective for relapse prevention in patients with recurrent major depression. It is well tolerated during long-term treatment for up to approximately one year.

Adult↗

Cyclooxygenase-2 expression in postmastectomy chest wall relapse.

PURPOSE: Cyclooxygenase-2 (COX-2) expression has been shown to be associated with radiation resistance, which theoretically could be overcome with the use of COX-2 inhibitors. The purpose of this study was to assess the prognostic significance and clinical correlations of COX-2 expression (COX) in a cohort of patients treated with radiation for postmastectomy chest wall relapse. EXPERIMENTAL DESIGN: Between 1975 and 1999, 113 patients were treated for isolated postmastectomy chest wall relapse. All patients were treated with biopsy and/or excision of the chest wall recurrence followed by radiation therapy. Median follow-up was 10 years. All clinical data, including demographics, pathology, staging, receptor status, HER-2/neu status, and adjuvant therapy, were entered into a computerized database. Paraffin-embedded chest wall recurrence specimens were retrieved from 42 patients, of which 38 were evaluated, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0 to 3+. A score of 2 to 3+ was considered positive. RESULTS: Overall survival from original diagnosis for entire cohort was 44% at 10 years. Survival rate after chest wall recurrence was 28% at 10 years. The distant metastasis-free survival rate after chest wall recurrence was 40% at 10 years. Local-regional control of disease was achieved in 79% at 10 years after chest wall recurrence. COX was considered positive in 13 of 38 cases. COX was inversely correlated with estrogen receptor (P = 0.045) and progesterone receptor (P = 0.028), and positively correlated with HER-2/neu (P = 0.003). COX was also associated with a shorter time to postmastectomy chest wall relapse. The distant metastasis-free rate for COX-negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2-positive patients (P = 0.029). COX positive had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX negative. This was of high statistical significance with a P value of 0.003. CONCLUSIONS: Outcome following radiation therapy for postmastectomy chest wall relapse is relatively poor. Positive COX correlated with other markers of poor outcome, including a shorter time to local relapse, negative estrogen receptor/progesterone receptor, and positive Her-2/neu status. Positive COX correlated with higher distant metastasis and lower local-regional control of disease. If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for postmastectomy chest wall relapse.

Adult↗

The prognostic value of p53 nuclear overexpression and MIB-1 as a proliferative marker in transitional cell carcinoma of the bladder.

BACKGROUND: There is controversy regarding the value of biologic markers as prognostic indicators independent of clinicopathologic parameters in transitional cell carcinoma (TCC) of the bladder. The authors examined the prognostic value of p53 tumor suppressor gene expression and the proliferative marker MIB-1 in TCC of the bladder. METHODS: Fresh frozen samples from 114 TCCs of the bladder and 13 normal bladders were studied by immunohistochemistry, using monoclonal antibodies MIB-1 for proliferation and PAb 1801 for p53 nuclear overexpression. Scores were determined in each case by counting at least 500 nuclei per slide in 3-5 selected regions. Patients were stratified for both markers into two groups for time-event analysis, according to the median number of nuclei stained. Patients with nuclear staining below the median value of the score were considered negative in the statistical analysis. Quantitative immunostaining was analyzed in relation to the time to recurrence, progression, and cancer death, and compared with clinical and pathologic parameters for prognostic significance in univariate and multivariate analysis (stepwise logistic regression). RESULTS: Median nuclear overexpression of p53 was 22% and that of MIB-1 28%. There was a strong association between proliferation and p53 nuclear overexpression (P < 0.0001). Progression free and disease specific survival rate estimates (log rank test) were significantly lower in patients with p53 or MIB-1 scores above 22% and 28%, respectively. Multivariate analysis indicated that stage as well as p53 and MIB-1 immunostaining provided independent prognostic information. CONCLUSIONS: Quantitative immunohistochemical evaluation of nuclear p53 and MIB-1 immunostaining inexpensively provides prognostic indicators in cases of TCC of the bladder.

Antibodies, Monoclonal↗

A narcolepsy susceptibility locus maps to a 5 Mb region of chromosome 21q.

The genetic basis of human narcolepsy remains poorly understood. Multiplex families with full-blown narcolepsy-cataplexy are rare, whereas families with both narcolepsy-cataplexy and excessive daytime sleepiness without cataplexy are more common. We performed a genomewide linkage analysis in a large French family with four members affected with narcolepsy-cataplexy and 10 others with isolated recurrent naps or lapses into sleep. Only three regions showed logarithm of odds (LOD) scores greater than 1 in two-point linkage analysis (D6S1960, D11S2359, and D21S228). Genotyping additional markers provided support for linkage to 9 markers on chromosome 21 (maximum two-point LOD score, 3.36 at D21S1245). The multipoint linkage analysis using SimWalk2 provided further evidence for linkage to the same region (maximum parametric LOD score, 4.00 at 21GT26K). A single haplotype was shared by all affected individuals and informative crossovers indicated that the elusive gene that confers susceptibility to narcolepsy is likely to be located between markers D21S267 and ABCG1, in a 5.15 Mb region of 21q.

Child↗