Isolated Pulmonary Cryptococcosis Confused with Lung Tumor 5 Years After Kidney Transplantation: A Case Report.

BACKGROUND: In transplant recipients, due to the use of immunosuppressive therapy, it is occasionally difficult to distinguish between an infection and malignancy, especially in the case of a lung lesion. Here, we report a case of isolated pulmonary cryptococcosis after kidney transplantation that was difficult to distinguish from a lung tumor. CASE REPORT: A 52-year-old man underwent a kidney transplant from his mother when he was 44 years old. Immunosuppression was maintained with tacrolimus, methylprednisolone, and mycophenolate mofetil. His post-transplant course was uneventful and serum creatinine levels were maintained. Five years post-transplantation, a non-contrast computed tomography (CT) examination revealed a nodule measuring 3 mm in diameter in the middle lobe of the right lung. The nodule gradually increased to 12 mm in 2 years. Positron emission tomography/CT examination showed a maximum standardized uptake value of 0.5 for the nodule. Biochemical examination revealed no elevation in total leucocyte count and C-reactive protein levels. However, tumor markers were elevated: serum carcinoembryonic antigen, 5.9 ng/mL; pro-gastrin-releasing peptide, 84.6 pg/mL. Furthermore, the serum cryptococcus antigen was negative. Therefore, thoracoscopic partial lung resection was performed. Pathologically, a number of spherical fungi from the necrotic substance of the tumor were confirmed positive by periodic acid-Schiff and Grocott-Gomori staining. The patient was therefore diagnosed with pulmonary cryptococcosis. Two years later, the patient is alive and has shown no evidence of recurrence. CONCLUSIONS: In lung nodules after kidney transplantation, even if serum cryptococcus antigen is not identified, it is necessary to keep in mind the possibility of pulmonary cryptococcosis.

Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation.

The purpose of this study was to investigate the accumulation of genetic alterations during metachronous and/or synchronous development of multifocal low-grade superficial urothelial tumours in the same patient, by using array-based comparative genomic hybridisation (array-CGH) and FGFR mutation analysis. We analysed 24 tumours (pTa-1 G1-2) from five patients. We had previously identified a clonal relationship among the tumours of each patient by microsatellite analysis. This time, unsupervised hierarchical cluster analysis revealed that the tumours from each patient were clustered together independently of the tumours from the other patients. All of the tumours from a single patient showed a set of 2-7 identical regional or whole-arm chromosomal changes. In addition, several individual alterations were also found. Cladistic diagrams revealed that the accumulation of genetic alterations could not be explained by a linear model, and the existence of a hypothetical precursor cell was assumed in four patients. In some cases, FGFR mutation seemed to occur later during multifocal tumour development. Taken together, these findings suggest that low-grade superficial urothelial tumours accumulate minor genetic alterations during multifocal development, although these tumours are genetically stable.

Dicoumarol potentiates cisplatin-induced apoptosis mediated by c-Jun N-terminal kinase in p53 wild-type urogenital cancer cell lines.

3-3'-Methylene-bis [4-hydroxycoumarin] (dicoumarol), an inhibitor of NADPH:quinone oxidoreductase 1, has been reported to possess potential antineoplastic effects and the ability to abrogate p53 protein. In the present study, we investigated the cytotoxic effects of dicoumarol in combination with cisplatin (CDDP), using four bladder (RT112, 253J, J82 and UMUC3) and two prostate (LNCap and PC3) cancer cell lines. Single treatment with 100 microM dicoumarol suppressed cell proliferation but did not induce apoptosis at 24 h in all cell lines examined. On the other hand, pretreatment with dicoumarol enhanced cytotoxicity of CDDP in three cell lines with wild type of p53 (RT112, 253J and LNCap), but not in three other cell lines with mutant p53 or in RT112 stable transfectants with a dominant-negative mutant of p53. In RT112 and LNCap, CDDP induced p53 and p21 expression, while pretreatment of dicoumarol suppressed induction of p53/p21 and resulted in sequential activation of c-Jun N-terminal kinase (JNK) in a time-dependent manner. Furthermore, inhibition of JNK, using SP600125, completely suppressed activity of caspases and poly-(ADP-ribose) polymerase cleavage, leading to suppression of enhancement of CDDP-mediated apoptosis by dicoumarol. These results suggested that dicoumarol could enhance cytotoxicity of CDDP in urogenital cancer cells with wild-type p53 through the p53/p21/JNK pathways.

Effect of NOS inhibitor on cytokine and COX2 expression in rat pulpitis.

Various kinds of chemical mediators are synthesized in the course of pulpitis; thus, control of their production would assist in inducing a reduction in pulpal inflammation. We hypothesized that nitric oxide (NO) would be an important mediator of pulpal inflammation. Pulpal inflammation was induced by the application of LPS in rat incisor pulp, and inducible nitric oxide synthase (iNOS) expression was evaluated by reverse-transcription/polymerase chain-reaction and immunohistochemical staining. After LPS application, iNOS mRNA was first detected after 3 hrs, peaked at 6 hrs, and decreased thereafter. iNOS-positive cells were macrophages and neutrophils. An NOS inhibitor caused drastic decreases in the expression of pro-inflammatory cytokines and COX2 mRNA, which was highly induced in the LPS-induced pulpitis. These results indicate that NO synthesis is related to the initiation of mediator production, and that its down-regulation should contribute to the prevention of pro-inflammatory mediator synthesis.

The pathogenesis and therapeutic option of encapsulating peritoneal sclerosis.

Since the first peritoneal dialysis (PD) patients with encapsulating peritoneal sclerosis (EPS) were reported in 1980, EPS has been considered primarily a fatal complication. The incidence of EPS in PD patients has been reported to be from 0.7% to 7.3%, and the rate appears to be higher in patients receiving long-term treatment. Most data from Japan has shown an overall incidence of 2.5% with an evident negative effect of increasing duration of PD, which also augments mortality. Since EPS occurred after withdrawal from PD in more than half of the patients, strict monitoring is necessary when a long-term PD patient is withdrawn from PD. Maintaining patients on standard PD for more than 8 years using conventional solutions is associated with a substantial risk for development of EPS. Appropriate treatment according to the disease stage is most important in EPS treatment. Therefore, when examining a PD patient complaining of gastrointestinal symptoms, the possibility of EPS has to be kept in mind. Basic therapeutic tactics for EPS include an appropriate use of steroids. If the state of bowel obstruction persists, laparotomy and enterolysis should be performed to obtain complete cure. It is now recognized that EPS is not a fatal complication of PD.

[Bladder carcinoma producing granulocyte colony-stimulating factor (G-CSF): a case report].

An 84-year-old male was admitted to our hospital with complaints of leg edema and general fatigue. He had undergone transurethral resection of transitional cell bladder cancer, grade 3, pT1b, one year previously. The computed tomographic scan revealed a hypoattenuating bladder tumor, protruding extravesically. Laboratory examination showed remarkable leukocytosis of 46,900/mm3 in the peripheral blood and high value of granulocyte colony-stimulating factor (G-CSF) 226 pg/ml (normal: less than 30 pg/ml). The resection of the tumor (partial cystectomy) was performed. The histological diagnosis was transitional cell carcinoma, grade 3. The production of G-CSF was confirmed by immunohistochemical examination in the recurrent tumor and the surgical sample from the transurethral resection. The leukocyte count in the peripheral blood decreased to the normal range after surgery. But leukocytosis recurred one month postoperatively and the computed tomographic scan revealed intrapelvic tumor recurrence. He died due to drastic progression of recurrent tumor at three months postoperatively.

Statistical analysis of diagnostic failure of fine needle aspiration cytology (FNAC) in breast cancer.

Fine-needle aspiration cytology (FNAC) was performed on 300 patients. Among those, 57 cases failed in accurate diagnosis of malignancy and 243 were successful. Fourteen clinicopathological factors altogether were analyzed to elucidate any correlation with FNAC failure using uni- and multivariate analysis. The univariate analysis in each clinicopathlogical factor showed that these error cases were vaguely palpable cancers, estrogen receptor (ER) positive cancers, small-sized of tumors, scattered type of cancer cell distribution in tumor tissues, with low tumor grade, with low Nottingham prognostic index (NPI), with benign-like ultrasound findings and with low TNM stage. The multivariate analysis revealed tumor grade was the strongest factor for all, followed by cellular distribution type of cancer cells and benign-like ultrasound findings. From these results, we speculated that diagnostic failure of FNAC at first clinic visit seemed to be caused by mainly two histocytological factors: extrinsic factor (structural factors of tissue-like tumor cells' distribution pattern, etc.); and intrinsic one (cellular factors of low atypism such as benign-like ultrasound finding, low tumor grade, and so on).

A utility of ductography and fiberoptic ductoscopy for patients with nipple discharge.

BACKGROUND: Breast carcinoma and precancer are thought to start in the lining of the milk duct or lobule. While ductography has been advocated as the main procedure in patients with nipple discharge, fiberoptic ductoscopy (FDS) is an emerging technique allowing direct visual access to the ductal system of the breast through nipple orifice exploration. METHODS: We applied ductography and FDS to 65 women who had nipple discharge, and compared their utility. RESULTS: Intraductal lesions occurred in the segmental duct and the first, second, third, fourth, fifth, and sixth branches in decreasing frequency with ductography and FDS screening. The detection rates of intraductal abnormal lesions by ductography and FDS and the their combination were 89.1 (37 patients), 97.4 (38 patients), and 97.5% (39 patients) respectively. Ductal washings performed during FDS were effective to obtain representative exfoliated ductal cells which could be evaluated (sensitivity 50%, specificity 94.3%, and diagnostic accuracy 89.7%). As a result, we diagnosed 35 cases of benign lesions and four cases of malignant lesions by cytological or/and histological examination. CONCLUSION: Ductography and fiberoptic ductoscopy are useful procedure in guiding subsequent breast surgery in the treatment of nipple discharge.

Encapsulating peritoneal sclerosis: definition, etiology, diagnosis, and treatment. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis.

Current definitions of encapsulating peritoneal sclerosis are practical and clinically relevant. It is important to adhere to a more uniform use of the proper terminology, and it is the recommendation of the authors that EPS be adopted as the more appropriate term. The best literal definition of EPS is based on clinical-pathologic criteria. Differentiation of EPS from the general category of ultrafiltration failure is required. Further, better appreciation of the diverse pathways that can lead to the same final common clinical-pathologic picture should not be overshadowed by the requirement of uniform terminology. Incidence and prevalence of the syndrome have been defined in some large populations and a few single-center experiences. The former show an incidence of less than 1%, while higher percentages are reported in the latter. The reported increased incidence with duration on therapy requires validation. The epidemiology of the syndrome offers limited insight into its pathogenesis. A list of factors, both dialysis-related and non dialysis-related. has been accumulated. Except in a few categories where agents are clearly related to the development of EPS, the majority of the listed factors for dialysis-related BPS remain, at best, associations and at worst, simple conjecture. The same limitations that plague the issue of etiology apply in the area of pathogenesis. More basic, focused work is required. The diagnosis of EPS remains based on clinical suspicion confirmed with, primarily, radiologic findings. Pathologic confirmation is obtained in cases that come to surgery for management or for catheter removal. Radiologic studies are precise enough for confirmation, but none have been evaluated for early diagnosis for possible early intervention or prevention. Studies based on transport characteristics or effluent dialysate constituents are not useful for EPS. At present, there are no reliable predictive tests for BPS that can be used in individual patients. Therapy of BPS is based on anecdotal evidence. The possible variable etiologies and probable distinct pathways leading to the syndrome may make a uniform therapeutic approach unlikely. Further, the limited number of cases and the sporadic pattern of occurrences make therapeutic trials not readily feasible. This is distinct from the case of ultrafiltration failure, where significant advances in mechanism elucidation and rationale-based interventions have been made.

Follicular dendritic cell sarcoma: ultrastructural and immunohistochemical studies.

A rare case of follicular dendritic cell (FDC) sarcoma is reported. A 71-year-old woman was admitted for evaluation of constipation. Computerized tomography showed cervical, supraclavicular, retroperitoneal, and paraaortic lymphadenopathies. Histological findings from a cervical lymph node revealed Hodgkin's disease at first. But tumors that arose both in the cervical and the left interscapular regions during the chemotherapy were immunohistochemically confirmed to be of follicular dendritic cell origin. The ultrastructural findings were consistent with those of FDC sarcoma. FDC sarcoma is a rare nonlymphoid cell-derived malignant tumor originating from the lymphoid tissue. The diagnosis of FDC sarcoma is most accurately established by immunohistochemical methods, using its specific markers.

Necessity of correcting cancer antigen 125 appearance rates by body surface area.

Attention has been focused on cancer antigen 125 (CA125) levels in dialysate as an index for evaluating the severity of peritoneal mesothelial cell impairment. However, the method of evaluating CA125 levels in the dialysate has not been standardized. We determined that CA125 levels in the dialysate should be corrected by body surface area (BSA). Using 51 patients who had been undergoing peritoneal dialysis (PD), CA125 levels in the dialysate were measured to evaluate the appearance rate of CA125 (CA125AR). Because only 18 of the 51 patients (35%) had a BSA greater than 1.73 m2, CA125 levels in the dialysate might be underestimated in other patients when absolute values of CA125 are not corrected by BSA. When correlations between corrected CA125AR and various parameters were evaluated, corrected CA125AR positively correlated with age, but negatively correlated with serum creatinine and albumin levels. Moreover, no positive correlation was seen between corrected CA125AR and the duration of PD or the peritoneal permeability test. However, in 5 patients with ultrafiltration loss after prolonged PD, the values of CA125AR persistently or rapidly decreased before transfer to hemodialysis. Although CA125 can be used as an index of peritoneal deterioration, the absolute value of CA125 should be corrected by BSA. However, it is most important to evaluate changes in CA125 in individual patients.

Surgical treatment for sclerosing encapsulating peritonitis.

Sclerosing encapsulating peritonitis (SEP) is recognized as a serious complication of continuous ambulatory peritoneal dialysis (CAPD). To date, in our hospital, 12 cases of SEP have been successfully treated by active intervention. The development of SEP was observed in these patients after removal of a peritoneal catheter. SEP was relieved by steroid administration in 3 of these patients, and by total parenteral nutrition (TPN) performed after exploratory laparotomy in 1 patient. In the remaining 8 patients, SEP was relieved by total intestinal enterolysis. In patients who underwent total intestinal enterolysis, the severity of encapsulation and adhesion varied. White, rigid encapsulation was observed in 4 patients who had been treated by peritoneal dialysis (PD) for less than 10 years. Seemingly normal serosae were observed under the capsules, and total intestinal enterolysis was easily performed in these patients. In the patient who underwent renal transplantation, more severe intestinal adhesion was observed, although the duration of PD was limited to 70 months and the intestinal serosae were seemingly normal. These findings were considered specific to SEP developing after immunosuppressant administration. In 3 patients who had undergone PD for more than 10 years, degeneration of the visceral peritoneum was observed, together with an ill-defined boundary between the capsules and the serosae. Therefore, total enterolysis was performed in these patients, including a wide area of the muscular layer. Furthermore, calcification was observed in several regions, where the capsules were severely adherent to the parietal peritoneum. The post-operative course for all 8 patients was satisfactory, and these patients finally returned to their previous social activities. We conclude that when SEP symptoms are not improved by steroid administration or TPN, active total intestinal enterolysis should be performed. However, it is absolutely important to avoid inducing anastomosis or impairing the intestine.

[Bellini duct carcinoma of the kidney: a case report].

This is a report of a case of Bellini duct carcinoma of the kidney. A 72-year-old male was admitted to our hospital for the treatment of left renal tumor. The abdominal computed tomographic scan showed hypoattenuating tumor with infiltrative spread into the renal cortex. The renal angiography revealed a hypovascular tumor. Left nephro-ureterectomy was performed because transitional cell carcinoma was suspected in the frozen section. The gross examination revealed an infiltrating white-gray tumor centered in the renal medulla. No hemorrhage was discovered, but partial necrosis was found. Capsular infiltration was not seen. Histologically, tumor cells were mostly scattered and partially showed a papillary and tubular structure. Cells had abundant eosinophilic cytoplasm and large irregular nuclei. Immunohistochemical studies revealed positive reactions for cytokeratin, epithelial membrane antigen and ulex europaeus agglutinin. We diagnosed this patient with Bellini duct carcinoma. He died due to drastic progression of metastasis from carcinoma two months postoperatively.

[Long-term results of ureteral replacement using ileum: report of four cases].

A total of four patients underwent ureteral replacement using ileum without the antireflux mechanism for extensive ureteral loss from 1985 to 1995. The indications included surgical trauma, retroperitoneal fibrosis, ureteral obstruction due to abscess, and ureteritis. One case had bilateral reconstruction. The followup interval ranged from 3 to 14 years. Urinary infections were noted in 2 cases. One patient, who had urinary infections and neurogenic bladder, had symptoms, but, in all cases, serum creatinine was unchanged or decreased and the pyelogram was normal or showed mild hydronephrosis. Thus, the procedure was considered successful in all cases. This procedure provides excellent long-term results for reconstruction of ureter when the normal ureter cannot be used. Creation of the antireflux mechanism may not be necessary in patients with normal renal function.

A solitary fibrous tumor in the perianal region with a 13-year follow-up: report of a case.

A case of a solitary fibrous tumor (SFT) of the perianal region in a 62-year-old man is reported herein. The patient had undergone an abdominoperineal excision of the rectum for an anorectal tumor 13 years previously, and had been referred to our hospital for a perineal mass. Computerized tomography and angiography revealed a markedly hypervascular tumor measuring 11 x 8 cm in size in the pelvic cavity. After preoperative radiotherapy (total 58 Gy) and the embolization of the feeding arteries, he underwent an en bloc excision of the tumor. Microscopically, the tumor was composed of spindle shaped cells with a "patternless" arrangement in a collagenous background. There was immunohistochemical evidence that these cells were strongly positive for CD34, thus suggesting the tumor to be SFT. The previously resected anorectal tumor showed similar histological and immunohistochemical findings. The patient's recovery was uneventful.

Malignant hemangioendothelioma of the small intestine: report of a case.

A case of malignant hemangioendothelioma (MH) of the small intestine in a 27-year-old woman is reported herein. The patient developed acute abdominal symptoms during investigations for anemia, weight loss, anorexia, and recurrent gastrointestinal bleeding. An emergency laparotomy revealed perforation of a jejunal tumor. The results of a histopathological study of the resected small bowel segment were interpreted as MH with lymph node involvement. Following this case report, a review of the relevant literature on small intestinal MH is presented.

Clinicopathologic and immunohistochemical analyses in lung metastasis of colorectal carcinoma.

We compared the immunohistochemical staining patterns of carcinoembryogenic antigen (CEA), CA19-9 and proliferating cell nuclear antigen (PCNA) between specimens from 13 patients who had undergone surgery for colorectal carcinoma with lung metastasis (lung metastasis group) and specimens from 13 patients who had no evidence of recurrence or metastasis within at least 5 years after colorectal resection (no metastasis group). The PCNA labeling indices of primary and metastatic lesions were 53.29 8.88% and 63. 26 6.21% (p<0.001), respectively. The PCNA labeling index in the no metastasis group was 26 12.9% (p<0.001). There was no significant difference in the CA19-9 staining patterns between the two groups. The CEA distribution patterns in the primary and lung metastatic lesions were different even in the same case. The original tumor cells showed apical or C1 localization, whereas metastatic cells showed C2 localization. These findings indicate that patients having colorectal carcinoma with a high PCNA labeling index have a high probability of lung metastasis, and that the CEA distribution pattern would change after original tumor resection.

Precise ultrastructural localization of endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in patients with IgA nephropathy.

Using light and electron microscopy, we performed an immunohistochemical study of endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in 15 patients with IgA nephropathy to clarify the localization of these adhesion molecules. The normal portions of 2 kidneys removed due to localized carcinoma and 3 biopsies from patients without glomerular disease were used as a control. By light microscopy, ELAM-1, VCAM-1, and ICAM-1 all showed positive staining in IgA nephropathy, with the intensity of staining following the sequence ICAM-1 > VCAM-1 > ELAM-1. ELAM-1 and VCAM-1 showed a patchy distribution of moderate staining in the tissues, including the mesangium, crescents, adhesions, and tubules. In contrast, there was marked linear ICAM-1 staining throughout the vascular walls. ELAM-1 and VCAM-1 were positive on the basolateral surfaces of a few proximal tubular epithelial cells in association with inflammatory cell infiltration, while ICAM-1 was found on the brush border. ICAM-1 was positive in the glomerular capillary walls and interstitial vessels of the control kidney tissue, while ELAM-1 and VCAM-1 were virtually absent. By electron microscopy, ELAM-1 positivity on the urinary surface of the parietal/visceral epithelial cells was often associated with adherent mononuclear cells in the urinary space. VCAM-1 positivity was increased in the perinuclear space and/or cytoplasm of mesangial cells as well as at the mesangial cell-endothelial cell interface. These findings suggest that ELAM-1 and VCAM-1 may be more closely related than ICAM-1 to the major histopathological changes occurring in IgA nephropathy, including mesangial expansion, formation of crescents and adhesions, and tubulointerstitial injury.

Chronic hepatitis B infection and autoimmune thyroiditis in Down syndrome.

Although it is well known that viral hepatitis can be complicated by autoimmune phenomena, the evidence for a pathogenetic role of viral hepatitis in the etiology of autoimmune thyroiditis is unclear. Because both hepatitis B and autoimmune thyroiditis occur frequently in Down syndrome, we decided to determine whether a cause-and-effect relationship might exist. Such a relationship might provide insight into basic mechanisms that could generalize to other populations. Accordingly, the frequency of hepatitis B surface antigen (HBsAg) positivity and thyroiditis was determined in 57 adults with Down syndrome and compared with frequencies in 450 age-, sex-, and environmentally matched mentally retarded patients without Down syndrome. We found no relationship of HBsAg positivity and thyroiditis in those mentally retarded patients without Down syndrome. On the other hand, the frequency of thyroiditis in those Down syndrome patients who were also carriers of HBsAg was threefold higher than the frequency of thyroid disease in those patients with Down syndrome who were not carriers of HBsAg (65% vs. 23%, p < 0.01). This relationship of hepatitis B and thyroid disease in Down syndrome might be explained by cytokine and/or cellular immune abnormalities linked to extra genetic material in trisomy 21. Clinically, patients with Down syndrome who are also hepatitis B carriers should be closely monitored for development of thyroid disease.

Angiosarcoma of the Breast: Immunohistochemical Demonstration of Steroid Receptors and Literature Review.

A 44-year-old female with bilateral angiosarcoma of the breast with multiple skin metastases is reported. She presented with a 6x8 cm and 1x1 cm mass in her left and right breasts, respectively, and multiple skin lesions around the chest. Histologically, the excised tumor was diagnosed as angiosarcoma of the breast with skin metastasis. Tumor cells were immunohistochemically positive with factor VIII-related antigen, CD34, alpha-smooth muscle actin and vimentin, and positive with UEA-I lectin. The majority of tumor cell nuclei expressed progesterone receptor (PgR) protein but estrogen receptro (ER) protein and androgen receptor (AR) protein were nagative. According to the literature, angiosarcoma of the breast mostly affects females in their fourth (33%) and fifth (40%) decades (mean age, 39.5 +/- 10.7 years). The survival rate depends on tumor size and tumor differentiation. The 3-year survival rate is 86% in patients with a tumor size less than 5 cm, and 90% in well-differentiated group I lesions.