Reassessment of T classification system cutoff value for renal cell carcinoma

PURPOSE: The 1997 T staging classification for renal cell carcinoma (RCC) defined T1 as tumors measuring up to 7 cm in size and T1 is subdivided into T1a and T1b with a 4 cm cutoff value in the 2002 TMN classification. We evaluated the validity of these cutoff values by assessing the cancer-specific survival of patients with non-metastatic RCC according to a series of alternative size cutoff values. In addition, we calculated how these size cutoffs affected the disease specific survival rates. MATERIALS AND METHODS: A database containing the records of 200 patients with RCC who underwent open radical nephrectomy for N0M0 disease between 1985 January and 2004 January was evaluated. Tumors were stratified by cutoff values ranging from 3 to 9 cm with the 1 cm increments in order to evaluate whether the 7 cm cutoff value is appropriate. Next, T1 RCC were stratified by cutoff values ranging from 3 to 6 cm with the 1 cm increment in order to verify whether the 4 cm cutoff is appropriate. Lastly, tumors over 7 cm diameter were stratified by cutoff values ranging from 9 to 14 cm with the 1 cm increments in order to verify whether the present T2-3a categories could be divided according to tumor size. RESULTS: As for the T1-2 classification, a cutoff value at 7 cm or 8 cm shared the greatest prognostic power. Although there was no significant difference in T1a/T1b subclassification, a 4 cm or 5 cm cutoff value resulted in a greatest separation of survival curves for T1a and T1b. As for tumors from 9-14 cm in diameter, only a 13 cm cutoff value provided a significant difference in survival. CONCLUSIONS: Our results indicate that the present 7 cm cutoff value in the TMN system is valid in terms of prognostic value. The 4 cm cutoff value may not reflect the survival when total nephrectomy is considered, thus indicating that tumors at 4 cm cutoff value may be valid when nephron sparing surgery is considered. The 13 cm cutoff value seems to be most appropriate in N0M0 tumors with over 7 cm in diameter.     

A case of ureteral malignant lymphoma diagnosed by laparoscopic needle biopsy

A pathological diagnosis of a lesion in the ureteral wall is often attended with a difficulty. We report a case of a 54-year-old man who presented a thickening of the ureteral wall and diffuse swelling of paraaortic lymph nodes diagnosed as a non-Hodgkin lymphoma by a laparoscopic needle biopsy. This is a safe and useful technique by which target tissues can be surely obtained.     

Downregulation of a newly identified laminin, laminin-3B11, in vascular basement membranes of invasive human breast cancers

Laminins present in the basement membranes (BM) of blood vessels are involved in angiogenesis and other vascular functions that are critical for tumor growth and metastasis. Two major vascular laminins, the α4 (laminin-411/421) and α5 (laminin-511/521) types, have been well characterized. We recently found a third type of vascular laminin, laminin-3B11, consisting of the α3B, β1 and γ1 chains, and revealed its biological activity. Laminin-3B11 potently stimulates vascular endothelial cells to extend lamellipodial protrusions. To understand the roles of laminin-3B11 in blood vessel functions and tumor growth, we examined localization of the laminin α3B chain in normal mammary glands and breast cancers, in comparison with the α4 and α5 laminins. In the immunohistochemical analysis, the α3B laminin was co-localized with the α4 and α5 laminins in the BM of venules and capillaries of normal breast tissues, but α3B was scarcely detected in vessels near invasive breast carcinoma cells. In contrast, the α4 laminin was overexpressed in capillaries of invasive carcinomas, where a large number of macrophages were found. The α5 laminin appeared to be weakly downregulated in cancer tissues, especially in capillary vessels. Furthermore, our in vitro analysis indicated that TNF-α significantly suppressed the laminin α3B expression in vascular endothelial cells, while it, as well as IL-1β and TGF-α, upregulated the α4 expression. These results suggest that Lm3B11/3B21 may be required for normal mature vessels and interfere with tumor angiogenesis.     

Degree of immobilization of synthetic RGDS(PO(3)H(2))PA peptides on titanium surfaces

The purpose of this study was to characterize the chemical interaction between titanium surfaces and the peptide RGDS(PO(3)H(2))PA (P-RGD) synthesized from RGD peptide (RGD) and o-phospho-L-serine (P-Ser), and to determine the degree of peptide immobilization on the titanium surface. X-ray photoelectron spectroscopy showed that the adsorption amount of RGD was significantly smaller than those of P-Ser and P-RGD (p<0.05). Furthermore, although it appeared that P-RGD bonded to the surface, ultrasonic rinsing with water caused it to dissociate, releasing RGD and leaving only S(PO(3)H(2))PA bonded to the surface. These findings show that although it remains difficult to obtain a stable P-RGD layer, the phosphate functional group greatly improves immobilization of the molecule on titanium surfaces.     

Use of mizoribine as a rescue drug for steroid-resistant pediatric IgA nephropathy

Recent clinical trials have shown a beneficial effect of mizoribine (Miz), an immunosuppressive drug, in the treatment of new-onset pediatric IgA nephropathy (IgAN). In this study, we evaluated the efficacy of Miz treatment in three children with established steroid-resistant IgAN. The patients had IgAN featuring persistent proteinuria and diffuse mesangial proliferation and had failed to respond to 2 years of treatment with prednisolone. Based upon the second biopsy results, patients were given methylprednisolone (mPSL) pulse therapy that induced a transient reduction in proteinuria, which was reversed when the mPSL dose was tapered. Miz therapy was then instigated in place of pulse mPSL. All three patients showed a substantial reduction in proteinuria and resolution of hematuria within 5 months. A follow-up biopsy in two of the patients showed a substantial reduction in the severity of glomerular lesions and a decrease in the number of activated macrophages. In conclusion, Miz therapy was found to be a safe and effective therapy in three cases of steroid-resistant pediatric IgAN. The ability of Miz to reduce the number of activated macrophages may be an important mechanism by which this drug ameliorated renal disease in these patients.     

Geriatric nutritional risk index as an easy-to-use assessment tool for nutritional status in hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Aim

The present study focused on Geriatric Nutritional Risk Index (GNRI), which is based on bodyweight and serum albumin, and known as an easy-to-use nutritional assessment tool in clinical settings, to elucidate the prognostic predictive ability of GNRI in patients treated with atezolizumab plus bevacizumab (Atez/Bev) for hepatocellular carcinoma (HCC).

Methods

A total of 525 HCC patients treated with Atez/Bev, based on their classification of unsuitable status for curative treatments and/or transarterial catheter chemoembolization, were enrolled (Child–Pugh A:B:C = 484:40:1, Barcelona Clinic Liver Cancer stage 0:A:B:C:D = 7:25:192:283:18). Prognosis was evaluated retrospectively using GNRI.

Results

Atez/Bev was used in 338 of the present cohort as first-line systemic chemotherapy (64.4%). Median progression-free survival based on GNRI indicating normal, mild decline, moderate decline, and severe decline was 8.3, 6.7, 5.3, and 2.4 months, respectively, whereas median overall survival was 21.4, 17.0, 11.5. and 7.3 months, respectively (both p < 0.001). The concordance index (c-index) values of GNRI for predicting prognosis (progression-free survival/overall survival) were superior to those of Child–Pugh class and albumin-bilirubin grade (0.574/0.632 vs. 0.527/0.570 vs. 0.565/0.629). As a subanalysis, muscle volume loss was observed in 37.5% of 256 patients with computed tomography data available. Along with GNRI decline, frequency of muscle volume loss became progressively larger (normal vs. mild vs. moderate vs. severe = 17.6% vs. 29.2% vs. 41.2% vs. 57.9%, p < 0.001), and a GNRI value of 97.8 was predictive of its occurrence (AUC 0.715, 95% CI 0.649–0.781; specificity/sensitivity = 0.644/0.688).

Conclusion

These findings indicate that GNRI is an effective nutritional prognostic tool for predicting prognosis and muscle volume loss complication in HCC patients treated with Atez/Bev.