Combined robotic and nonrobotic telepathology as an integral service component of a geographically dispersed laboratory network.

To achieve real-time connectivity between its 8 hopital-based laboratories, Veterans Integrated Service Network (VISN) 12, headquartered in Chicago, IL, has implemented a hybrid dynamic store-and-forward (HDSF) telepathology network that extends across portions of 3 states. The majority of diagnostic telepathology functions are provided to the 3 hospitals (Iron Mountain, MI; Tomah, WI; and North Chicago, IL), which lack on-site pathologists and are serviced by the 4 pathologists located in Milwaukee, WI. In surgical pathology, routine primary diagnosis, frozen section diagnosis, and clinical consultation are provided with telepathology. In addition, autopsy and specialty clinical conferences are frequently performed by using telepathology. Telepathology has been applied to a variety of areas within clinical pathology as well, including protein electrophoresis, immunoelectrophoresis, peripheral blood smears, body fluids, microbiology, and distance learning. Implementation of telepathology has allowed VISN 12 to reach the goal of providing a single standard of accurate and timely pathology service, even at small sites that lack an on-site pathologist.

Telepathology networking in VISN-12 of the Veterans Health Administration.

The Veterans Integrated Service Network (VISN)-12, headquartered in Chicago, has implemented a telepathology network between the eight VISN-12 hospital laboratories and Loyola University Medical School linked by an economical, high-speed wide-area network (WAN). Implementation of the WAN has reduced monthly telecommunications costs in VISN-12 by approximately 67%. In addition to telepathology, the WAN enables real-time teleradiology (general, computer tomography, and ultrasound), telefluoroscopy, telenuclear medicine imaging, telepsychiatry, and other forms of teleconsultation. Current applications of telepathology in VISN-12 include: primary diagnosis and consultation in surgical pathology, interpretation of serum protein electrophoresis and immunofixation gels, provision of support for consolidated microbiology laboratories, review of problematic peripheral blood smears, and distance learning. We have learned a variety of lessons from telepathology. The enthusiasm and technical skill of providers are essential for success. As well, frequent communication and rapid technical support are necessary. Finally, in a supportive environment, telepathology is a tool that can help bring together clinical laboratories with shared missions and goals.

Routine surgical telepathology in the Department of Veterans Affairs: experience-related improvements in pathologist performance in 2200 cases.

OBJECTIVE: To determine whether diagnostic concordance, case deferral rate, and/or time required to review slides changed significantly as telepathologists gained additional experience using a hybrid dynamic/store-and-forward (HDSF) telepathology (TP) system on the 2000 cases following an initial 200 consecutive surgical cases, previously reported. MATERIALS AND METHODS: Gross surgical pathology specimens were prepared by specially trained personnel in Iron Mountain, Michigan. For TP, glass slides were placed on the stage of a robotic microscope at the Iron Mountain VAMC (remote site); control of the motorized microscope was then transferred to a pathologist located 220 miles away at the Milwaukee, Wisconsin, VAMC (host site). For each case, a telepathologist had the option of either rendering a diagnosis or deferring the case for later analysis by conventional light microscopy (LM). After the slides were read by TP and a surgical pathology report had been generated (for nondeferred cases), the slides were transported to Milwaukee, where they were reexamined by the same pathologist, now using LM. When there was disagreement between the TP and LM diagnosis, a supplemental or revised report was issued, and the referring physician was notified by telephone immediately. All supplemental and revised reports were reviewed by a third pathologist in the group. The slides were then reviewed by the pathology group practice or, when there was no consensus, by the Armed Forces Institute of Pathology to establish a "truth" diagnosis. To determine changes in telepathologist performance with experience after the initial start-up of the service, their performance in handling 10 consecutive sets of 200 surgical pathology cases was analyzed. RESULTS: Concordance rates for clinically significant TP and LM diagnoses were high for all 10 sets, ranging from 99% to 100%. Comparing the first set (Cases 201-400) with the last set (Cases 2001-2200), viewing times per case were reduced from 10.26 min to 3. 58 min. Viewing times per slide were reduced from 3.44 min to 1.13 min per slide, comparing the first and last sets. Case turnaround times (TAT) decreased from 2.46 days to < or =1.5 days. CONCLUSION: Thes results demonstrate that improvements in TP services occur over time as the result of additional experience using the TP system. The high diagnostic concordance and low rate of case deferral lend additional support to the proposal that a host-site pathologist using HDSF TP can substitute effectively for an on-site pathologist as a service provider.

L-arginine uptake and metabolism by lung macrophages and neutrophils following intratracheal instillation of silica in vivo.

Nitric oxide (NO) has been associated with lung inflammation following exposure to silica. L-arginine can be converted to NO and L-citrulline by nitric oxide synthase (NOS), or into urea and L-ornithine by arginase. We tested the hypothesis that after instillation of silica into rat lungs in vivo, lung inflammatory cells increase L-arginine metabolism by both NOS and arginase, which is associated with an increase in L-arginine uptake. We isolated lung inflammatory cells 3 d after silica or saline (control) exposure. The uptake of [3H]L-arginine at 24 h by cells from silica-exposed lungs (73.9 +/- 4.8%) was significantly greater than uptake by control cells (24.7 +/- 2.2%; P < 0.05) and was a saturable process. The greater [3H]L-arginine uptake by cells from silica-exposed lungs was associated with greater NO and urea production than by control cells. The uptake of [3H]L-arginine by cells from control or silica-exposed lungs was blocked in a dose-dependent manner by L-ornithine (an inhibitor of L-arginine transport) and by Nomega-nitro-L-arginine methyl ester (L-NAME) (an NOS inhibitor), but not by L-valine (an arginase inhibitor). The production of NO by cells from silica-exposed lungs was completely blocked by L-NAME. The addition of L-arginine to media resulted in dose-dependent production of NO and urea. The results show that lung inflammatory cells increase L-arginine uptake and metabolism by both NOS and arginase following in vivo silica exposure. The increase in L-arginine uptake may represent a mechanism to maintain an intracellular supply of this amino acid. NO can react to generate peroxynitrite, a potential mediator of lung injury following silica exposure.

Use of telepathology for routine surgical pathology review in a test bed in the Department of Veterans Affairs.

BACKGROUND: Routine surgical pathology review by telepathology could be an important service component of multi-institutional pathology laboratory systems. Such service networks would increase access for rural hospitals without on-site pathologists to a broader range of pathology services on a daily basis. METHODS: In this clinical trial, we analyzed the diagnostic accuracy, deferral rates, and viewing times of two generalist pathologists using a hybrid dynamic/store-and-forward (HDSF) telepathology (TP) system to render diagnoses in real time on 200 consecutive surgical cases. The objective was to assess the efficacy of TP in providing diagnostic surgical pathology services to a remote hospital without an onsite pathologist. Surgical pathology specimens underwent gross preparation by specially trained personnel. When appropriate, this was done under the video supervision of a telepathologist. For TP, glass slides were placed on the stage of a robotic microscope at the Iron Mountain (MI) Department of Veterans Affairs Medical Center (VAMC) (remote site); control of the motorized microscope was then transferred to a pathologist located 220 miles away at the Milwaukee VAMC (host site). For each case, the telepathologist had the option of rendering a diagnosis or deferring the case for later analysis by conventional light microscopy (LM). After the slides were read by TP and a surgical pathology report had been generated, the slides were transported to Milwaukee, where they were reexamined by the telepathologist using LM and then by the pathology group practice or, when there was no consensus, by an outside consultant to establish a "truth" diagnosis. RESULTS: Compared with the consensus ("truth") diagnosis, clinically important and overall concordance were 99.0% and 97.4%, respectively, by TP, and clinically important and overall concordance were 100.0% and 98.5%, respectively, by LM. The deferral rate was 2.5%. Examining glass slides by HDSF telepathology took an average of 4.43 minutes per slide and 12.09 minutes per case. CONCLUSION: The high diagnostic accuracy and low rate of case deferral support the proposal that an offsite pathologist using HDSF telepathology can substitute effectively for an onsite pathologist as a service provider.

Dynamic-robotic telepathology: Department of Veterans Affairs feasibility study.

In this retrospective study, we assess the accuracy, confidence levels, and viewing times of two generalist pathologists using both dynamic-robotic telepathology and conventional light microscopy (LM) to render diagnoses on a test set of 100 consecutive routine surgical pathology cases. The objective is to determine whether telepathology will allow a pathology group practice at a diagnostic hub to provide routine diagnostic services to a remote hospital without an on-site pathologist. For TP, glass slides were placed on the motorized stage of the robotic microscope of a telepathology system by a senior laboratory technologist in Iron Mountain, MI. Real-time control of the motorized microscope was then transferred to a pathologist in Milwaukee, WI, who viewed images of the glass slides on a video monitor. The telepathologists deferred rendering a diagnosis in 1.5% of cases. Clinically important concordance between the individual diagnoses rendered by telepathology and the "truth" diagnoses established by rereview of glass slides was 98.5%. In the telepathology mode, there were five incorrect diagnoses out of a total of 197 diagnoses. In four cases in which the telepathology diagnosis was incorrect, the pathologist's diagnosis by LM was identical to that rendered by telepathology. These represent errors of interpretation and cannot be ascribed to telepathology. The certainty of the pathologists with respect to their diagnoses was evaluated over time. Results for the first 50 cases served as baseline data. For the second 50 cases, confidence in rendering a diagnosis in the telepathology mode was essentially identical to that of making a diagnosis in the LM viewing mode. Viewing times in the telepathology mode also improved with more experience using the telepathology system. These results support the concept that an off-site pathologist using dynamic-robotic telepathology can substitute for an on-site pathologist as a service provider.

Annular constriction of the rectum secondary to transitional cell carcinoma of the bladder.

Recurrent transitional cell carcinoma of the bladder is often a locally progressive disease. Regional lymph node metastasis is a frequent finding and may be the first sign of recurrence. Involvement of the gastrointestinal tract is rare, but metastasis to the colon, small intestine, and stomach have been reported. Herein, we present a case of recurrent transitional cell carcinoma of the bladder manifesting as an annular constricting mass of the rectum, and review the literature regarding this unusual lesion.

Hydroxyl radical production and lung injury in the rat following silica or titanium dioxide instillation in vivo.

The hydroxyl radical (.OH) is a highly reactive oxygen free radical that has been implicated as a cause of lung injury following exposure to silica and silicates. Despite evidence that silica generates .OH in vitro, there has been no previous demonstration of in vivo production of .OH after exposure to nonfibrous mineral oxide dusts. We tested the hypothesis that instillation of silica into rat lungs is associated with greater .OH production and acute lung inflammation in vivo relative to the instillation of a less toxic nonsilicate particle, titanium dioxide. The production of .OH in the lungs following dust instillation was measured using sodium salicylate as an .OH trap. Seven days after dust exposure, the rats were given intraperitoneal salicylate, the lungs isolated, and salicylate hydroxylation products (2,3- and 2,5-dihydroxybenzoic acid), reflecting .OH, were measured. There was significantly more 2,3-dihydroxybenzoic acid in silica-exposed lungs compared with lungs instilled with titanium dioxide. In addition, the instillation of silica into rat lungs in vivo was associated with a greater acute inflammatory response. We conclude that following in vivo exposure, silica stimulates greater .OH production relative to the less toxic particle, titanium dioxide. These differences in .OH generation correspond to disparities in acute lung inflammation.

Kaposi's sarcoma of the oral cavity in a non-AIDS patient: case report and review of the literature.

BACKGROUND: Not every patient with Kaposi's sarcoma (KS) has acquired immunodeficiency syndrome (AIDS). The "classic" form of KS is rare, and is associated with an indolent course. It is very distinct from AIDS-associated KS in which oral involvement is common and may be the initial presenting feature of this disease. Two other types of KS are recognized, the African and renal transplant-associated, which also are rarely associated with oral involvement. METHODS: We present the case of a 76-year-old man of Mediterranean ancestry who was found to have a biopsy-proven classical KS lesion of the hard palate. The patient was followed by the Radiation Therapy and Otolaryngology Services during and after his treatment. A review of the literature was also conducted. RESULTS: Radiotherapy was ineffective at a dose considered "standard" for KS in AIDS patients (1,500 cGy), but was effective when continued to 4,800 cGy. A 24-month follow-up showed no evidence of recurrence in the oral cavity. CONCLUSIONS: KS of the oral cavity, is almost always associated with AIDS in the United States, However, it can occur in any of the four types of KS. Although this neoplasm is typically highly radiosensitive, the treatment for each patient needs to be individualized.

Oxidative stress as a precursor to the irreversible hepatocellular injury caused by hyperthermia.

Heat-induced hepatotoxicity accompanying hyperthermic liver perfusion was studied in the isolated, haemoglobin-free perfused rat liver. Trypan blue uptake, a sensitive indicator of cell death, was used to examine the relationship between the efflux of oxidized glutathione (oxidative stress), the appearance of cytosolic enzymes in the perfusate and cell death. Livers were perfused at 37, 42, 42.5 and 43 degrees C. The efflux of total glutathione (GSH) and oxidized glutathione (GSSG) increased with time and temperature. Differences between temperature groups were significant for both parameters for 37 versus 42, 42.5 and 43 degrees C (p less than 0.05). Temperature-related differences in GSH levels appeared at 15 min for 37 versus 42 degrees C and in GSSG levels at 30 min for 37 versus 42 and 42.5 degrees C. Biliary excretion of total GSH increased from 72 nmol at 37 degrees C to 144 nmol at 42 degrees C, 160 nmol at 42.5 degrees C and 124 nmol at 43 degrees C, which was significant for 37 versus 42 and 42.5 degrees C (p less than 0.05). The release of allantoin into the perfusate, a measure of purine catabolism and flux through xanthine oxidase, was increased at 42, 42.5 and 43 degrees C compared to 37 degrees C (p less than 0.05). Liver injury was assessed by measuring the release of asportate aminotransferase (AST) and lactate dehydrogenase (LDH) and uptake of trypan blue after perfusion at each temperature. There was a pronounced release of LDH and AST into the perfusate after 60 min of perfusion at 42, 42.5 and 43 degrees C, the levels of which were significantly different from the 37 degrees C mean level. There was no uptake of trypan blue after 60 min perfusion at 37 degrees C. Perfusion at 42, 42.5 and 43 degrees C resulted in the uptake of trypan blue in the pericentral areas, but the dye uptake was significant (p less than 0.05) compared to 37 degrees C at 42.5 and 43 degrees C only. These data show that heat-induced pericentral cell death is minimal after 60 min at 42-43 degrees C, and that the biochemical process which occurred during this period suggest 'oxidative stress' as a causative factor in hyperthermic hepatotoxicity. In addition, this liver toxicity is probably related to xanthine oxidase activity or the depletion of GSH as the initiating event which leads to lipid peroxidation and cellular damage.

Idiopathic pulmonary fibrosis. A rare cause of scintigraphic ventilation-perfusion mismatch.

A case of idiopathic pulmonary fibrosis with multiple areas of mismatch on ventilation-perfusion lung imaging in the absence of pulmonary embolism is presented. Idiopathic pulmonary fibrosis is one of the few nonembolic diseases producing a pulmonary ventilation-perfusion mismatch. In this condition, chest radiographs may not detect the full extent of disease, and xenon-133 ventilation imaging may be relatively insensitive to morbid changes in small airways. Thus, when examining patients with idiopathic pulmonary fibrosis, one should be aware that abnormal perfusion imaging patterns without matching ventilation abnormalities are not always due to embolism. In this setting, contrast pulmonary angiography is often needed for accurate differential diagnosis.

Richter's syndrome presenting as primary central nervous system lymphoma. Transformation of an identical clone.

The development of a central nervous system (CNS) large cell lymphoma in a patient simultaneously diagnosed with chronic lymphocytic leukemia (CLL) is reported. Although differences in phenotypic expression were demonstrated in study of the peripheral blood and CNS disease, identical immunoglobulin gene rearrangements were identified, providing evidence for evolution of two morphologically distinct neoplasms from the same clone. Beyond histologic transformation, acquisition of an aneuploid cell population in the CNS tumor was demonstrated by analysis of DNA content. Isolated parenchymal involvement of the CNS by large cell transformation of CLL has not been previously described; its relationship to CNS lymphoma and Richter's syndrome are reviewed.

Cardiovascular ochronosis: a case report and review of the medical literature.

Ochronosis is a rare disorder of tyrosine metabolism due to a deficiency of the enzyme homogentisic acid oxidase. The most common clinical manifestations include alkaptonuria, spondyloarthropathy, large joint arthritides and pigmentation of cartilage. Cardiac involvement may occur due to the deposition of polymerized homogentisic acid in the aortic, mitral and pulmonic valves. Usually, this leads to increasing rigidity and calcification. The only functionally significant valve lesion reported appears to be aortic stenosis. A possible link between ochronosis and coronary artery disease has been postulated. Further, a link between peripheral vascular disease and ochronosis may be present. We describe a case of ochronotic cardiovascular disease and review the literature on the subject.

Leukemia of the penis.

Leukemia of the penis is an extremely rare entity. A case involving the distal penis is described, and the relevant evaluation and treatment are discussed. Only 2 other documented cases of penile leukemia are found in the literature. Identification and treatment of the underlying etiology are important aspects of this unusual disease entity.

Tuberculous epididymitis occurring 35 years after renal tuberculosis.

An unusual case of tuberculous epididymitis occurring 35 years after renal tuberculosis is reported. The possible mechanisms of this delayed presentation of the epididymal lesion are discussed. This case emphasizes the importance of adequate treatment as well as long-term followup of patients with genitourinary tuberculosis.

Primary renal carcinoid tumor.

A case of primary renal carcinoid tumor in a sixty-seven-year-old man is presented. Radical nephrectomy removed the primary disease, but hepatic metastases developed and the patient subsequently died. Review of the literature disclosed 8 other cases of primary renal carcinoid. Three of these had metastatic spread.

The association of adult respiratory distress syndrome (ARDS) with thoracic irradiation (RT).

The authors report two cases of apparent adult respiratory distress syndrome (ARDS) following limited thoracic irradiation for lung cancer. Respiratory failure followed rapidly after irradiation with diffuse bilateral infiltrates, both in and out of the irradiated volume along with progressive hypoxemia unresponsive to oxygen management. Other potential causes of lung injury such as lymphangitic tumor, cardiac failure, and infections were excluded by both premortem and postmortem examination. Autopsy findings in both irradiated and unirradiated volumes of lung were consistent with hyaline membrane changes. The possible relationship between radiation therapy to limited lung volumes and the development of adult respiratory distress syndrome is discussed.

Metastatic tumors involving testis.

Two cases of metastatic tumors involving the testis are reported: one from an adenocarcinoma of the prostate and the other from an adenocarcinoma of the colon. The first was found incidentally in the orchiectomy specimen done for prostatic cancer while the other was noted clinically as a part of a widely disseminated disease. Although there are numerous pathways through which tumors may metastasize to the testis, the occurrence of testicular metastasis is extremely rare. The reason for this rarity remains unknown.

The role of radiation therapy in the treatment of recurrent adult laryngeal papillomatosis.

Laryngeal papillomatosis is an uncommon condition in the adult, but it can be severe enough to require tracheostomy for obstructive changes following multiple recurrences, despite surgical local excisions and medical therapies. Few satisfactory treatments are available for such cases to restore both airway function and speech. Some patients may require laryngectomy for progressive dysfunction. The role of radiation therapy has been controversial, with some reports of malignant transformation following treatment. The authors describe two cases treated with irradiation, resulting in complete clearance of the lesions and return of airway and vocal function. Follow-up is given, and the available literature is reviewed.