Case of primitive neuroectodermal tumor of the kidney

A 28-year-old woman presented with right flank pain. A large, firm, fixed mass was palpable in the right side of the abdomen. Computed tomography revealed a solid mass of the right kidney with extension into the renal vein and inferior vena cava. The patient underwent right radical nephrectomy with en bloc resection of the inferior vena cava containing tumor thrombus and right adrenalectomy. Histologically the tumor consisted of small tumor cells with rosette formation. Immunohistochemical staining was positive for CD99 and NSE. Analysis with polymerase chain reaction (PCR) demonstrated the EWS/FLI1 fusion products resulting from a chromosomal translocation. These findings were consistent with primary renal primitive neuroectodermal tumor (PNET). Two months after surgery, multiple lung, liver and lymph node metastases were found. The patient received 2 cycles of chemotherapy with cisplatin, ifosfamide, etoposide, resulting in a partial remission. She subsequently received 1 cycle chemotherapy with paclitaxel and carboplatin, resulting in no response. The metastatic lung and liver diseases progressed and she died 5 months after diagnosis.     

Survival and sinus rhythm maintenance after modified Cox/maze procedure and mitral valve operation in patients with chronic atrial fibrillation

OBJECTIVE: Sinus rhythm gained after the Cox/maze procedure concomitant with mitral valve operation has demonstrated long-term attrition during the follow-up, no information exists on whether the type of mitral valve operation--(repair vs. replacement)--affects this sinus rhythm maintenance rate. We retrospectively studied patients undergoing concomitant mitral valve operation and Cox/maze procedure to answer this question. METHODS: Between April 1993 and August 1995, 87 consecutive patients--35 men and 52 women (mean age: 59.3 years)--with chronic atrial fibrillation and mitral valve disease underwent the modified Cox/maze procedure and concomitant mitral valve operation, with 56 having mitral valve repair (repair group) and 31 mitral valve replacement (replacement group). Patients were followed up and changes in rhythm studied retrospectively. RESULTS: Follow-up for a mean 51.3 +/- 11.6 months was completed in 82 of 83 long-term survivors (99%). Repair group surgery survival was 98.1 +/- 1.9% at 1 year and 94.2 +/- 3.2% at 5 based on the Kaplan-Meier method. Replacement group surgery survival was 85.7 +/- 5.9% at 1 year and 82.9 +/- 6.4% at 5. Probability in sinus rhythm maintenance for the repair group at 1 year was 88.6 +/- 5.4% and at 5 years was 67.6 +/- 9.1%. Probability in sinus rhythm maintenance for the replacement group at 1 year was 95.7 +/- 4.3% and at 5 years was 65.0 +/- 11.1%. CONCLUSIONS: Medium-term results after the Cox/maze III procedure concomitant with mitral valve operation are good. The attrition of sinus rhythm maintenance appears similar by the completion of 5-year follow-up.     

Comparison of surgical results after pneumonectomy and sleeve lobectomy for non-small cell lung cancer: trends over time and 20-year institutional experience.

OBJECTIVE: Sleeve lobectomy is a lung-saving procedure for central tumors for which the alternative is pneumonectomy. The purpose of this study was to report the clinical characteristics, operative results, survival, and late outcomes over 20 years in patients who underwent sleeve lobectomy and pneumonectomy at our institution. METHODS: There were 62 patients who underwent sleeve lobectomy (SL group) and 110 who underwent pneumonectomy (PN group). Comparisons of the demographics, morbidity, and survivals between the groups were performed by unpaired t-test, chi(2)-test, and log-rank test. RESULTS: Patients who underwent a pneumonectomy showed a significantly advanced pathological stage, and a larger tumor size than those who received a sleeve lobectomy, whereas there were no significant differences in histology, ratio of combined resection and induction therapy, or total morbidity. There were three in-hospital deaths (4.8%) in the SL group and four (3.6%) in the PN group. Local relapse and distant recurrence incidence were similar between the two groups. The 5-year-survival rates of the SL and PN groups were 54% and 33%, respectively (p<0.0001). However, there were no differences in 5-year survivals in patients with pathological stage I/II (SL, 59% vs PN, 63%) and those who received induction therapy (SL, 22% vs PN, 52%) between the groups. CONCLUSIONS: Both pneumonectomy and sleeve lobectomy were performed with an acceptable risk of operative mortality and satisfactory 5-year survival rate. The indication of pneumonectomy is aimed to perform a curative resection for locally advanced lung cancer, particularly after induction therapy that is otherwise unresectable, and the selected patients will likely benefit from a complete resection.     

Role of heat shock protein 47, a collagen-binding chaperone, in lacrimal gland pathology in patients with cGVHD

PURPOSE: Uncontrolled fibrosis due to excessive accumulation of extracellular matrix proteins in the lacrimal glands of patients with chronic graft-versus-host disease (cGVHD) is well documented. Heat-shock protein 47 (HSP47) is involved in the molecular maturation of collagen and has been shown to have a fibrogenic role in various fibrotic diseases. In this study, the role of HSP47 in the pathogenesis of lacrimal gland of patients with cGVHD was investigated. METHODS: The expression of HSP47, Ki67 (a proliferation marker), types I and III collagen, and alpha-smooth muscle actin (alpha-SMA) was examined in tissue sections and in primary cultures of fibroblasts obtained from the lacrimal glands of patients with cGVHD (n = 8) and Sj?gren's syndrome (SS; n = 7). RESULTS: Tissue sections of the lacrimal glands of patients with cGVHD showed markedly increased expression of HSP47 in fibroblasts around the medium-sized ducts than did those from patients with SS. The elevated expression of HSP47 in patients with cGVHD was mostly detected in Ki67-positive fibroblasts and was associated with increased accumulation of types I and III collagen in and around the fibrotic areas. Primary fibroblast cultures generated from cGVHD lacrimal gland showed higher HSP47 mRNA expression than did fibroblasts isolated from SS biopsy tissue, as determined by RT-PCR (P < 0.05). In contrast, alpha-SMA was higher in the SS than cGVHD fibroblasts at both mRNA and protein levels, and more lacrimal gland fibroblasts in the SS were positive for alpha-SMA than cGVHD (P < 0.01). CONCLUSIONS: In cGVHD, increased expression of HSP47 may promote excessive collagen assembly in and around the periductal areas where fibroblasts are mostly in an active state. The less alpha-SMA in the cGVHD lacrimal gland fibroblasts suggests a relative lack of myofibroblastic transformation. It is likely that fibroblasts incapable of myofibroblastic transformation are the main source of HSP47 and collagen production, and the resultant effect is the periductal fibrotic changes seen in lacrimal glands of patients with cGVHD.     

Optical mapping reveals developmental dynamics of Mg2+-/APV-sensitive components of glossopharyngeal glutamatergic EPSPs in the embryonic chick NTS

To examine whether there are any differences in functional organization between the glossopharyngeal nerve (N. IX)- and vagus nerve (N. X)-projecting areas in the nucleus of the tractus solitarius (NTS), we performed optical recording of neural responses evoked by N. IX stimulation in 5- to 9-day-old embryonic chick brain stem preparations and compared the results with those in our previous studies concerning the N. X-related NTS. First, we investigated DL-2-amino-5-phosphonovaleric acid (APV)/Mg2+ sensitivity of the glutamatergic excitatory postsynaptic potentials (EPSPs) in the N. IX-related NTS. In 7- to 9-day-old preparations, we found regional differences in the degree of both the APV-induced reduction and Mg2+-free-induced enhancement of the EPSPs. We constructed developmental maps of spatial patterns of the APV- and Mg2+-sensitive components and showed that functional expression of the N-methyl-D-aspartate (NMDA) receptor dynamically changed during development. Second, we studied initial expression of synaptic functions in the N. IX-related NTS. In 6-day-old preparations, although action potentials alone were usually detected in normal Ringer solution, small EPSPs were elicited in a Mg2+-free solution. This result suggests that the NMDA receptor-mediated synaptic function is latently generated in the N. IX-related NTS at the 6-day-old embryonic stage and that external Mg2+ regulates the onset of synaptic functions. Developmental patterns of APV/Mg2+ sensitivity and the stage of initial expression of the glossopharyngeal EPSP were similar to those of the N. X, suggesting that the developmental sequence of the synaptic function in the NTS is the same for the N. IX- and N. X-related NTS.     

Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis

Leg ulcers are often complicated in patients with rheumatoid arthritis (RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers.     

Effect of activated human mast cells and mast cell-derived mediators on proliferation,type I collagen production and glycosaminoglycans synthesis by human dermal fibroblasts

Although an increased number of mast cells in fibrotic tissues such as scleroderma, keloid or healing wound has been highlighted, it is still unclear whether or not mast cells are fibrogenic. The aim of the present study is to determine whether functionally active human mast cells can provide human dermal fibroblasts directly with fibrogenic properties. In order to examine the effects of IgE-mediated mast cell activation on fibroblast proliferation and synthesis of type I collagen, we utilized an in vitro defined system in which cultured human mast cells were co-cultured with human dermal fibroblasts. We also employed a three-dimensional fibroblast culture system using supplementation of L-ascorbic acid as an assay system to investigate the effects of mast cell-derived mediators on synthesis of glycosaminoglycans by human fibroblast. Fibroblast proliferation was actively stimulated with IgE-activated mast cells. However, this stimulatory effect was canceled in co-cultures with a higher number of IgE-activated mast cells. In the presence of a higher number of activated mast cells, the fibroblast cell layer was destroyed, in contrast to an intact cell layer in the presence of same number of the mast cells without activation. Type I collagen synthesis was unchanged in fibroblasts co-cultured with mast cells. The total amount of main disaccharide units, particularly DELTADi-HA, was increased when fibroblasts were exposed to histamine. Thus, we conclude that other factors, in addition to mast cells, are important in the development of human tissue fibrosis or sclerosis.     

T cells and mast cells as a major source of interleukin-13 in atopic dermatitis

BACKGROUND: Interleukin (IL)-13 is a T-cell-derived cytokine that shares several functions with IL-4, including the induction of immunoglobulin E synthesis. Recent studies suggest that cytokines expressed locally in the skin play several critical roles in atopic dermatitis (AD), however, little is known about the role of IL-13 in AD lesions. OBJECTIVES: The present study was designed to characterize the involvement of IL-13 in AD in the skin and peripheral blood mononuclear cells (PBMC). METHODS: Using lesional and nonlesional skin from adult AD patients and normal skin from healthy volunteers, we performed RT-PCR, in situ RT and immunostaining to determine the IL-13 expression at the mRNA and protein levels. The actual numbers of IL-13 expressing cells in biopsy specimens were counted under the microscope. IL-13 mRNA expression in PBMC from AD patients and healthy volunteers was examined by RT-PCR analysis. RESULTS: IL-13 mRNA expression was detected by RT-PCR in lesional and nonlesional skin and in PBMC from AD patients, but not in normal skin or PBMC from healthy volunteers. In AD lesional skin, numerous IL-13 mRNA-positive cells were demonstrated by in situ RT, and similar numbers of IL-13-positive cells were also detected immunohistochemically. Smaller numbers of IL-13-positive cells were observed in AD nonlesional skin and in normal skin. The differences in the numbers of IL-13-expressing cells between lesional and nonlesional skin were statistically significant. Double immunostaining revealed that IL-13 was produced in approximately 40% of T cells and 20% of mast cells in AD lesional skin, suggesting that T cells and mast cells are major sources of IL-13 in AD lesions. CONCLUSION: IL-13 may play a local as well as a systemic role in the development of AD lesions.