Papillary urothelial neoplasm of low malignant potential: reliability of diagnosis and outcome

OBJECTIVE To determine the ability of pathologists to reproducibly diagnose a newly defined lesion, i.e. the papillary urothelial neoplasm of low malignant potential (PUNLMP) using the published criteria, defined by the 1998 World Health Organisation/International Society of Urological Pathology (WHO/ISUP) classification system; in addition, debate remains about the clinical behaviour of these lesions, thus the rates of recurrence and progression of PUNLMP lesions were assessed and compared with low-grade papillary urothelial carcinomas (LG-PUC) and high-grade (HG-PUC) over a 10-year follow-up. PATIENTS AND METHODS Forty-nine cases of superficial bladder cancer (G1-3 pTa) representing an initial diagnosis of transitional cell carcinoma made in 1990 were identified and re-graded using the 1998 WHO/ISUP classification by two pathologists. Inter-observer agreement was assessed using Cohen weighted kappa statistics. After reclassification the clinical follow-up was reviewed retrospectively, and episodes of recurrence and progression recorded. RESULTS The inter-observer agreement was moderate, regardless of whether one (kappa 0.45) or two (kappa 0.60) pathologists were used to grade these lesions. Re-classification identified 12 PUNLMP, 28 LG-PUC and nine HG-PUC. PUNLMP lesions recurred in 25% (3/12) of cases; no progression was documented. Recurrence rates were 75% (21/28) and 67% (6/9) for LG- and HG-PUC, respectively, and progression rates were 4% (1/28) and 22% (2/9). CONCLUSION The 1998 WHO/ISUP classification of urothelial neoplasms can be reproducibly applied by pathologists, with a moderate level of agreement. There is evidence that PUNLMP lesions have a more indolent clinical behaviour than urothelial carcinomas. However, the risk of recurrence and progression remains, and clinical monitoring of these patients is important.

Endothelin axis expression is markedly different in the two main subtypes of renal cell carcinoma

BACKGROUND. The endothelin axis has been implicated in cancer growth, angiogenesis, and metastasis, but to the authors' knowledge the expression of endothelin genes has not been defined in renal cell carcinoma (RCC). METHODS. Tissue specimens were harvested from both normal and tumor-affected regions at the time of radical nephrectomy from 35 patients with RCC (22 with clear cell RCC [ccRCC] and 13 with papillary RCC [PRCC]). Real-time reverse transcriptase-polymerase chain reaction analysis determined the expression profile of the preproendothelins (PPET-1, PPET-2, and PPET-3), the endothelin receptors (ETA and ETB), and the endothelin-converting enzymes (ECE-1 and ECE-2). RESULTS. PPET-1 was found to be up-regulated in ccRCC tumor specimens and down-regulated in PRCC tumor specimens. ETA was significantly down-regulated in PRCC tumor specimens. ECE-1 was expressed in all tissue specimens at comparable levels, with moderate but significant elevation in normal tissue specimens associated with PRCC. Of the other genes, PPET-2 and ETB were expressed in all tissue specimens and no differences were observed between tumor subtypes or tumor-affected and normal tissue specimens, whereas PPET-3 and ECE-2 were present in all tissue specimens but were barely detectable. CONCLUSIONS. The endothelin axis was expressed differently in the two main subtypes of RCC and appeared to match macroscopic features commonly observed in these tumors (i.e., high expression of PPET-I in hypervascular ccRCC contrasted against low PPET-1 and ETA expression in hypovascular PRCC). The presence of ECE-1 mRNA in these tissue specimens suggested that active endothelin ligands were present, indicating endothelin axis activity was elevated in ccRCC compared with normal kidney, but impaired in PRCC. The current study provided further evidence that it is not appropriate to consider ccRCC and PRCC indiscriminately in regard to treatment. (C) 2004 American Cancer Society.

Medial upper eyelid shortening to correct medial eyelid laxity in floppy eyelid syndrome: A new surgical approach

Purpose: To describe and present the results of a new surgical technique for patients with floppy eyelid syndrome, based on the medial upper eyelid stretching encountered in this condition. Methods: A case series of 24 patients with floppy eyelid syndrome who where found to have symptomatic predominately medial upper eyelid laxity was analyzed. The history, clinical features, histopathology, and outcome were reviewed after patients underwent medial upper eyelid shortening with or without upper eyelid skin reduction as the first surgical procedure. Results: Of the 24 patients, 18 were men (75%) with a mean age at referral of 56 years, having ocular discomfort and conjunctival irritation/papillary conjunctivitis as the main complaints at presentation. Obesity was present in 96% of cases, with lower eyelid laxityl/ectropion (50%) and upper eyelid eyelash ptosis (29%) in conjunction with the upper eyelid laxity. The affected side was related to sleeping habits or recurrent mechanical eyelid trauma. Histologic studies showed a nonspecific inflammatory cell infiltrate and loss of elastin with loose dermal connective tissue. After surgery, complete relief of ocular symptoms and good functional and cosmetic results were present in all cases after 18 months of follow-up. Conclusions: This new surgical approach is based on the presence of predominately medial upper laxity in patients with floppy eyelid syndrome. The excision of this stretched area stabilized the upper eyelid in an anatomic fashion, providing a good and stable long-term result. The possible mechanisms involved in the medial upper eyelid stretching are discussed.