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R A Schmidt

Publications and source records attributed to R A Schmidt.

At least 37 records · Page 2Linked to original sources

Lung cancer proliferation correlates with [F-18]fluorodeoxyglucose uptake by positron emission tomography.

Tumor proliferation has prognostic value in resected early-stage non-small cell lung cancer (NSCLC). We evaluated whether [F-18]fluorodeoxyglucose (FDG) uptake of NSCLC correlates with tumor proliferation and, thus, could noninvasively grade NSCLCs (refining patient prognosis and therapy). Thirty-nine patients with potentially resectable NSCLC underwent whole-body FDG positron emission tomography (PET) 45 min after i.v. injection of 10 mCi of FDG. Tumor FDG uptake was quantitated with the maximum pixel standardized uptake value (maxSUV). The lesion diameter from computed tomography was used to correct the maxSUV for partial volume effects using recovery coefficients determined for the General Electric Advance PET scanner. Thirty-eight patients underwent complete surgical staging (bronchoscopy and mediastinoscopy, with or without thoracotomy). One stage IV patient by PET underwent bronchoscopic biopsy only. Immunohistochemistry for Ki-67 (proliferation index marker) was performed on all of the 39 NSCLC specimens (35 resections, 1 percutaneous, and 3 surgical biopsies). The specimens were reviewed for cellular differentiation (poor, moderate, well) and tumor type. Lesions ranged from 0.7 to 6.1 cm. The correlation found between uncorrected maxSUV and lesion size (Rho, 0.56; P = 0.0006) disappeared when applying the recovery coefficients (Rho, -0.035; P = 0.83). Ki-67 expression (percentage of positive cells) correlated strongly with FDG uptake (corrected maxSUV: Rho, 0.73; P < 0.0001). The correlation was stronger for stage I lesions (11 stage IA, 15 stage IB): Rho, 0.79; P < 0.0001) and strongest in stage IB (Rho, 0.83; P = 0.0019). A significant association (P < 0.0001) between tumor differentiation and corrected SUV was noted. FDG PET may be used to noninvasively assess NSCLC proliferation in vivo, identifying rapidly growing NSCLCs with poor prognosis that could benefit from preoperative chemotherapy.

Disease Progression↗

Pretreatment scalene node biopsy in gynecologic malignancy: prudent or passé?

OBJECTIVES: Surgicopathologic evaluation of the scalene fat pad is considered a critical step in the pretreatment evaluation of patients at our institution with cervical or corpus carcinoma when the periaortic lymph nodes (PAN) are involved. However, enthusiasm for this procedure at other centers has waned, largely due to a wide discrepancy in the reported rates of occult scalene node involvement. In an attempt to clarify the benefit of pretreatment scalene node sampling in gynecologic malignancies, we present our experience over the past 18 years. MATERIALS AND METHODS: We identified 57 patients who underwent scalene node sampling between 1980 and 1998. In 39 of 49 (80%), the decision to proceed with scalene node sampling was based entirely on histologically documented PAN metastases. In the remainder, scalene node sampling was prompted by the presence of suspicious clinical findings. RESULTS: Of the 49 patients included in the study, 33 had carcinoma of the cervix, while 16 had corpus carcinoma. Ninety percent of scalene node sampling was performed at the time of primary diagnosis. Overall, 9 patients (18%) had scalene node metastases. Notably, not a single patient with corpus cancer was found to have scalene node metastases in the absence of clinically evident scalene node enlargement independent of PAN status. In cervix cancer cases, the presence of grossly involved PAN was predictive of a high likelihood of scalene node metastases (44%), while no patient with occult PAN metastases had involvement of the scalene node. Only 1 minor complication was encountered following scalene node sampling. The 40 scalene node-negative patients were treated with either extended field radiation or whole abdominal radiation therapy, and 20% developed a major, RTOG grade >/=3 complication such as fistula formation, bowel obstruction, or ureteral stenosis. Only 1 case of mild radiation enteritis and cellulitis occurred during palliative radiation in the group of patients with scalene node metastases. CONCLUSIONS: Scalene node sampling may be of benefit in the pretreatment evaluation of patients with cervical carcinoma when PAN are grossly involved. Given that scalene node involvement satisfies the criteria for distant metastases, identification of such allows the clinician to avoid the morbidity of extended field radiotherapy in a setting without the chance for cure.

Biopsy↗

Improving breast cancer diagnosis with computer-aided diagnosis.

RATIONALE AND OBJECTIVES: The purpose of this study was to test whether computer-aided diagnosis (CAD) can improve radiologists' performance in breast cancer diagnosis. MATERIALS AND METHODS: The computer classification scheme used in this study estimates the likelihood of malignancy for clustered microcalcifications based on eight computer-extracted features obtained from standard-view mammograms. One hundred four histologically verified cases of microcalcifications (46 malignant, 58 benign) in a near-consecutive biopsy series were used in this study. Observer performance was measured on 10 radiologists who read the original standard- and magnification-view mammograms. The computer aid provided a percentage estimate of the likelihood of malignancy. Comparison was made between computer-aided performance and unaided (routine clinical) performance by using receiver operating characteristic (ROC) analysis and by comparing biopsy recommendations. RESULTS: The average ROC curve area (Az) increased from 0.61 without aid to 0.75 with the computer aid (P < .0001). On average, with the computer aid, each observer recommended 6.4 additional biopsies for cases with malignant lesions (P = .0006) and 6.0 fewer biopsies for cases with benign lesions (P = .003). This improvement corresponded to increases in sensitivity (from 73.5% to 87.4%), specificity (from 31.6% to 41.9%), and hypothetical positive biopsy yield (from 46% to 55%). CONCLUSION: CAD can be used to improve radiologists' performance in breast cancer diagnosis.

Area Under Curve↗

Sacral nerve stimulation and diurnal urine volume.

OBJECTIVES: During a screening trial to determine candidacy for sacral nerve stimulation (SNS), several patients were required to repeat the baseline dietary because of discrepancies in the 24-hour urine output before and after successful stimulation. This raised a question regarding the relationship between urine production and neuromodulation. A more complete diary analysis of patients affected by urgency/frequency and/or urge incontinence was therefore carried out to evaluate the possibility of a direct modulatory influence of SNS on urine production. METHODS: Voiding diaries of 40 patients (37 females and 3 males, average age 39.4 years) who underwent SNS were evaluated. Voiding diaries were obtained at baseline, during and after peripheral nerve evaluation (PNE) and after permanent implantation. RESULTS: There was an increase in the average volume/void during PNE in 39 patients. Twenty-four-hour urine volume during PNE was statistically greater than that at baseline. Volume/void and diurnal volume were also significantly greater in follow-up periods after permanent implantation. CONCLUSION: SNS appears to influence not only bladder function but also urine production. Increase in volume/void is paralleled by an increase in 24-hour urine output. The mechanism is unclear, but it is consistent with an altered release of antidiuretic hormone. This observation reflects the direct refractory involvement of the hypothalamus in micturition.

Adolescent↗

The accuracy of the clinical diagnosis of new-onset idiopathic pulmonary fibrosis and other interstitial lung disease: A prospective study.

STUDY OBJECTIVES: Presently, surgical (open or thoracoscopic) lung biopsy (SLB) is the gold standard for the diagnosis of new-onset idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). The accuracy of a clinical diagnosis of IPF and other subsets of ILD has never been established in prospective studies. We investigated the accuracy and validity of a clinical diagnosis of IPF and ILD other than IPF. DESIGN: Prospective, independent evaluation of patients and clinical data by an ILD expert, of chest radiographic and high-resolution computed tomography (HRCT) features by a chest radiologist, and of histologic features of lung biopsy by a pulmonary pathologist in consecutive patients referred for a diagnostic evaluation of ILD. SETTING: Tertiary university medical center with recognized expertise in management of ILD. PATIENTS: Community patients referred for further definitive diagnostic evaluation of new-onset, untreated nonspecific ILD. INTERVENTION: By comparing the histologic features of SLB in 59 patients consecutively referred for further diagnostic evaluation of new-onset ILD with the clinical and radiologic diagnoses, we determined the sensitivity and specificity of clinical diagnosis and radiologic diagnosis (based on chest radiograph and HRCT features alone) of IPF and ILD other than IPF. A specific clinical diagnosis was independently made by the ILD expert after a thorough clinical assessment that included evaluation of an HRCT scan and bronchoscopic findings. The chest radiographs and HRCT scans were separately reviewed by the chest radiologist, who made a radiologic diagnosis independently. All patients underwent SLB within a month of preoperative "clinical" diagnosis. The clinician's and radiologist's diagnoses were then compared with the gold standard of histologic diagnosis. MEASUREMENTS AND RESULTS: Prior to the clinical evaluation at our center, 85% of patients who underwent SLB had nondiagnostic transbronchial biopsy. The diagnosis of IPF and ILD other than IPF was accurately made by clinical features alone in 62% of cases. The correct radiographic diagnosis of non-IPF ILD was made in 58% of the cases. The sensitivity and specificity of the clinical diagnosis of ILD other than IPF were 88.8% and 40%, respectively. The sensitivity and specificity of the radiographic diagnosis of ILD other than IPF were 59% and 40%, respectively. However, the sensitivity and specificity of the diagnosis of IPF on clinical grounds were 62% and 97%, respectively. The sensitivity and specificity of the radiologic diagnosis of IPF were 78.5% and 90%, respectively. CONCLUSIONS: In a center with recognized expertise in the management of ILD, the specificity of diagnosis of new-onset IPF based on a thorough clinical assessment or HRCT features alone is very high (97% and 90%, respectively), but the sensitivity is low (62% and 78.5%, respectively). Thus, not all patients with new-onset IPF require SLB for diagnosis, but a diagnosis of IPF will be missed in nearly one third of new-onset IPF cases despite evaluation by experts. The relatively low sensitivity and specificity of the diagnosis of ILD other than IPF also emphasizes that an SLB is indicated in patients with ILD in whom the diagnosis is unclear.

Adult↗

Neurourological insights into the etiology of genitourinary pain in men.

PURPOSE: Pelvic pain remains a challenging urological problem. Because antimicrobial therapy is often unsuccessful for relieving symptoms, it is reasonable to question whether pelvic pain is the result of microbiological versus functional pelvic disease. We analyzed clinical and urodynamic findings to evaluate the role of pelvic floor dysfunction in patients with pelvic pain. MATERIALS AND METHODS: We retrospectively evaluated history, physical examination and urodynamic studies in 103 men with an average age of 47 years who presented with pelvic pain between August 1994 and August 1997. In all patients microbiological tests were negative before study entry. RESULTS: The reported locations of pain were the prostate and/or perineal region in 45.6% of cases, scrotum and/or testis in 38.8%, penis in 5.8%, bladder in 5.8%, and lower abdomen and lower back in 1.9% each. Previous treatment consisted of 1 to 12 courses of antibiotics in the preceding 6 to 36 months. In 88.3% of the patients there was pathological tenderness of the striated muscle with poor to absent pelvic floor function. Urodynamics were performed in 84 cases. Cystometry was normal except for decreased compliance in 5 patients. Abnormal findings were mostly evident in the coordination of voiding and in dynamic sphincter-pelvic floor activity. Average sphincter pressure was increased to 104.9 cm. water in 72.6% of the patients, average peak urine flow was decreased to 9.9 ml. per second in 61.9% and functional urethral length was increased to greater than 35 mm. in 79.8%. Urethral profile pattern was dysfunctional, obstructed, and combined dysfunctional and obstructed in 52.4, 11.9 and 21.4% of the cases, respectively, while in 88.1% urethral sensitivity was minimally or markedly increased. CONCLUSIONS: Since activity is a reflection of neural control, the apparent association of pelvic floor dysfunction with pelvic pain raises the probability of a primary or secondary central nervous system breakdown in the regulation of pelvic floor function. This hypothesis is supported by the improvement in symptoms caused by therapy aimed at modulating the pelvic floor, such as biofeedback, medication and sacral anterior root stimulation.

Adult↗

Sacral nerve stimulation for treatment of refractory urinary urge incontinence. Sacral Nerve Stimulation Study Group.

PURPOSE: A prospective, randomized study was performed to evaluate sacral nerve stimulation for the treatment of refractory urinary urge incontinence. MATERIALS AND METHODS: Primary outcome variables were obtained from voiding diaries. After baseline evaluation candidates who satisfied inclusion criteria were enrolled into the study. Test stimulation results determined eligibility for randomization into a stimulation (treatment) or delay (control) group. The stimulation group included 34 patients who underwent implantation and were followed for 6 months. The delay group comprised 42 patients who received standard medical therapy for 6 months and then were offered implantation. The stimulation group completed a therapy evaluation test (on versus off) after 6 months. RESULTS: At 6 months the number of daily incontinence episodes, severity of episodes and absorbent pads or diapers replaced daily due to incontinence were significantly reduced in the stimulation compared to the delay group (all p<0.0001). Of the 34 stimulation group patients 16 (47%) were completely dry and an additional 10 (29%) demonstrated a greater than 50% reduction in incontinence episodes 6 months after implantation. Efficacy appeared to be sustained for 18 months. During the therapy evaluation test the group returned to baseline levels of incontinence when stimulation was inactivated. Urodynamic testing confirmed that sacral nerve stimulation did not adversely affect voiding function. Complications included implantable pulse generator site pain in 15.9% of the patients, implant site pain in 19.1% and lead migration in 7.0%. Surgical revision was required in 32.5% of patients with implants to resolve a complication. There were no reports of permanent injury or nerve damage. CONCLUSIONS: Sacral nerve stimulation is safe and effective in treating refractory urinary urge incontinence.

Adult↗

Thyroid transcription factor-1: immunohistochemical evaluation in pulmonary neuroendocrine tumors.

Thyroid transcription factor-1 (TTF-1), a nuclear transcription protein selectively expressed in the thyroid, the diencephalon, and respiratory epithelium, is expressed in more than 90% of pulmonary small cell carcinomas (SCLCs) and in almost 75% of pulmonary non-small cell carcinomas (NSCLCs), but it is absent in typical pulmonary carcinoids (TCs). Therefore, it was thought that SCLC and NSCLC might share a common lineage, different from that of TC. TTF-1 expression in atypical pulmonary carcinoids (ACs) and large-cell neuroendocrine carcinomas (LCNECs) was not studied previously. We examined TTF-1 expression in 51 TCs, 9 ACs, 8 LCNECs, and 21 SCLCs with use of formalin-fixed material and heat-induced epitope retrieval. TTF-1 expression was seen in 18 (35%) of 51 TCs, all of the 9 ACs, 6 (75%) of the 8 LCNECs, and 20 (95%) of the 21 SCLCs. These results reinforce earlier findings of the excellent sensitivity of TTF-1 for SCLC, and they show similar sensitivity for AC and LCNEC, but they argue against the hypothesis that SCLC and TC are of different cell lineages. The ubiquity of TTF-1 expression in pulmonary NECs demonstrated in this study also argues against its use in their subclassification.

Carcinoid Tumor↗

Botox-induced prostatic involution.

BACKGROUND: A simple approach to induced prostatic atrophy was explored. Surgical denervation is known to produce profound atrophy of the rat prostate. Because Botulinum toxin type A (Botox) produces a long-term chemical denervation, the potential to induce atrophy of the rat prostate was explored. METHODS: Thirty rat prostates were injected with varying doses of Botox. Single and serial injections were used, and rats were subsequently sacrificed after either 1 or 4 weeks, respectively. The prostate glands were harvested, weighed, and histologically studied for morphologic and apoptotic changes. RESULTS: The total prostate volume and weight were found to be reduced in all Botox-injected animals. Histologically, a generalized atrophy of the glands was observed with the H&E stain. There was also diffuse glandular apoptosis evident with the Tunel stain. There were no significant complications (e.g., urinary retention, weight loss, or hind/limb weakness). CONCLUSIONS: Botulinum toxin type A injection into the prostate gland induces selective denervation and subsequent atrophy of the prostate. Apoptosis was seen diffusely throughout the gland. It may be possible that in the future, this long-acting neurotoxin could be used for the treatment of common pathologies of the human prostate.

Animals↗

Successful treatment of severe hepatitis C-associated pulmonary vasculitis in a liver transplant recipient.

BACKGROUND: We report the clinical course of a patient who developed fever, hypoxia, and bilateral pulmonary infiltrates two and a half years after orthotopic liver transplantation (OLT) for cirrhosis due to hepatitis C. The patient had a history of hepatitis C-associated vasculitis manifested by purpuric skin rashes, renal abnormalities, and elevated cryoglobulins, and was receiving interferon-alpha at the time of presentation. RESULTS: The results of bronchoscopy with bronchoalveolar lavage were unrevealing, and open lung biopsy revealed active small vessel vasculitis. The patient responded dramatically to plasmapheresis and the addition of high-dose corticosteroids with resolution of hypoxia, pulmonary infiltrates, and glomerulonephritis. This is, to our knowledge, the first report of the successful treatment of hepatitis C-associated pulmonary vasculitis after OLT. CONCLUSIONS: We conclude that hepatitis C-associated pulmonary vasculitis should be included in the differential diagnosis of a patient presenting with fever, hypoxia, and pulmonary infiltrates after OLT for hepatitis C. Treatment with plasmapheresis and high-dose corticosteroids may be effective in patients with this disorder.

Adrenal Cortex Hormones↗

Central autonomic innervation of the lower urinary tract--a neuroanatomy study.

Knowledge about the central innervation of the lower urinary tract is limited. The spinal cord and the pontine micturition center have been investigated most thoroughly, whereas high centers have received little attention. Pseudorabies virus (PRV), a self-amplifying and transneuronal tracer was injected into the bladder trigone of 21 Sprague-Dawley rats. The animals were killed after 72, 96, and 120 h. The whole CNS was sectioned and immunostained for PRV. CNS centers directly connected to the bladder include the intermedio lateral cell column, the central autonomic nucleus, and the nucleus intercalatus at the spinal cord levels T12-L2 and L6-S2. The raphe pallidus et magnus, the A5 nor-adrenergic area, the pontine micturition center, the locus coeruleus, the periaquaductal gray, the nucleus para- et periventricularis of the hypothalamus, the red nucleus, the medial preoptic area, and the cortex are supraspinal centers connected to the bladder. Lower urinary tract function is a complex multilevel and multineuronal interaction. It involves facilitation and inhibition at many levels of the CNS.

Animals↗

Postoperative chronic pain and bladder dysfunction: windup and neuronal plasticity--do we need a more neurological approach in pelvic surgery?

PURPOSE: Cases of combined symptoms of dysfunctional voiding and associated pelvic discomfort are difficult diagnostic and therapeutic challenges. Surgical solutions not uncommonly fail to relieve those symptoms. We determine why these symptoms persist postoperatively. MATERIALS AND METHODS: Four cases of ureteral injury during gynecological laparoscopic procedures for pelvic/menstrual pain are presented. The cases are reviewed for their severity and similarity in presenting symptoms, complications and long-term consequences. RESULTS: In all cases light pain symptoms and/or dysfunctional voiding problems that existed before the initial surgery escalated severely after corrective pelvic surgery. CONCLUSIONS: There are established neurophysiological mechanisms that would explain the observed increase in pain after surgical manipulation of the pelvis. Windup and changes in neuronal plasticity are direct consequences of wounding and/or neural injury to the central nervous system. These principles are important for surgeons to appreciate due to the impact they can have on the outcomes of surgery. Blocking the sensory input into the spinal cord, inherent to every surgical procedure, through use of local anesthetics, that is preemptive anesthesia, before creation of a wound provides the greatest protection against escalation of symptoms. Thorough evaluation of all patients before pelvic surgery is recommended to identify high risk groups (preexisting pain, voiding syndromes).

Adult↗

Automated computerized classification of malignant and benign masses on digitized mammograms.

RATIONALE AND OBJECTIVES: To develop a method for differentiating malignant from benign masses in which a computer automatically extracts lesion features and merges them into an estimated likelihood of malignancy. MATERIALS AND METHODS: Ninety-five mammograms depicting masses in 65 patients were digitized. Various features related to the margin and density of each mass were extracted automatically from the neighborhoods of the computer-identified mass regions. Selected features were merged into an estimated likelihood of malignancy by, using three different automated classifiers. The performance of the three classifiers in distinguishing between benign and malignant masses was evaluated by receiver operating characteristic analysis and compared with the performance of an experienced mammographer and that of five less experienced mammographers. RESULTS: Our computer classification scheme yielded an area under the receiver operating characteristic curve (Az) value of 0.94, which was similar to that for an experienced mammographer (Az = 0.91) and was statistically significantly higher than the average performance of the radiologists with less mammographic experience (Az = 0.81) (P = .013). With the database used, the computer scheme achieved, at 100% sensitivity, a positive predictive value of 83%, which was 12% higher than that for the performance of the experienced mammographer and 21% higher than that for the average performance of the less experienced mammographers (P < .0001). CONCLUSION: Automated computerized classification schemes may be useful in helping radiologists distinguish between benign and malignant masses and thus reducing the number of unnecessary biopsies.

Breast Neoplasms↗

Poorly differentiated synovial sarcoma: immunohistochemical distinction from primitive neuroectodermal tumors and high-grade malignant peripheral nerve sheath tumors.

Synovial sarcoma is a relatively common sarcoma in adults, which in its classic bimorphic form infrequently poses a diagnostic problem. Monomorphic spindled variants, as well as the less common poorly differentiated variants, may be confused with other soft-tissue sarcomas; the poorly differentiated variant (PDSS), in particular, may be histologically indistinguishable from other small, blue, round cell tumors, including primitive neuroectodermal tumors (PNETs). Detection of the synovial sarcoma-associated t(X;18) by either cytogenetic or molecular genetic approaches may be necessary to confirm the diagnosis of synovial sarcoma in difficult cases. We evaluated 10 cases of PDSS from eight patients using a panel of antibodies (including those to intermediate filament proteins, nerve-sheath associated markers, and neuronal and neuroectodermal associated markers) in order to better establish the immunophenotype of this tumor and to help distinguish it from the tumors with which it may be confused, particularly PNETs and high-grade malignant peripheral nerve sheath tumors (MPNSTs). Our results showed PDSS to have significant immunophenotypic overlap with both PNETs and MPNSTs. In most instances these three entities may be differentiated by a panel of antibodies that should include those to both low and high molecular weight cytokeratins, epithelial membrane antigen, type IV collagen, CD99, CD56, and S-100 protein. Our results also suggest that synovial sarcoma may be a tumor showing combined neuroectodermal and nerve sheath differentiation--perhaps because of translocation-associated expression of specific proteins--rather than a carcinosarcoma of soft tissues or a tumor of specialized arthrogenous mesenchyme.

12E7 Antigen↗