Soluble tumour necrosis factor receptor type II and survival in colorectal cancer.

BACKGROUND: Chronic inflammation may play a role in colorectal cancer (CRC) pathogenesis. The relationship between soluble tumour necrosis factor receptor type II (sTNF-RII) and survival among CRC patients is not well defined. METHODS: We prospectively evaluated the association between pre-diagnosis plasma levels of sTNF-RII and mortality in 544 CRC patients from the Nurses' Health Study and Health Professionals Follow-Up Study diagnosed from 1990 to 2010. Primary and secondary end points were overall and CRC-specific mortality, respectively. Cox proportional hazards models were used to calculate multivariate hazard ratios for mortality. RESULTS: Higher sTNF-RII levels were significantly associated with increased overall mortality (multivariate HR=1.48, 95% CI 1.02-2.16, P-trend=0.006), but not with CRC-specific mortality (HR=1.23, 95% CI 0.72-2.08, P-trend=0.34). In subgroup analyses, among regular aspirin users, those with higher sTNF-RII levels had an adjusted HR of 0.52 (95% CI 0.20-1.33) for overall mortality compared with those with lower sTNF-RII levels, whereas among nonregular aspirin users the adjusted HR was 2.26 (95% CI 1.23-4.01, P for interaction=0.53). CONCLUSIONS: Among CRC patients, higher sTNF-RII levels are associated with a significant increase in overall mortality, but not CRC-specific mortality. The role of inflammation and anti-inflammatory medications in survival of CRC patients warrants further exploration.

The effect of 595 nm pulsed dye laser on superficial and nodular basal cell carcinomas.

BACKGROUND AND OBJECTIVE: Basal cell carcinomas (BCCs) have supporting vasculature that could serve as a target for 595 nm pulsed dye laser (PDL). The objective of this study was to determine the effect of repeated PDL treatments on BCCs of superficial and nodular subtypes and of varying diameters. STUDY DESIGN/MATERIALS AND METHODS: Twenty biopsy-proven BCCs received four 595 nm PDL treatments at 2-week intervals. The tumor and 4 mm of peripheral skin were treated using a set of previously optimized laser parameters: one pass, 15 J/cm2 energy, 3 ms pulse length, no cooling, and 7 mm spot size with 10% overlap. The treated area was excised and evaluated histologically for residual tumor. Histologic response rates of the PDL treated BCCs were compared with that of non-PDL treated, matched control tumors. RESULTS: Nearly all BCCs <1.5 cm in diameter (n = 12) showed complete response to four PDL treatments (91.7%; n = 11/12) versus 16.7% of controls (n = 2/12, P-value = 0.0003). BCCs > or =1.5 cm in diameter (n = 8) showed a complete response rate of 25% (n = 2/8) versus 0% of controls (n = 0/8, P-value = 0.2). Mean clinical tumor diameter of the complete responders was 1.1 cm (n = 13) versus 2.2 cm (n = 7) for incomplete responders (P-value = 0.005). Tumor histologic types among the complete responders included superficial, nodular, micronodular, and keratinizing. Incompletely responding BCCs showed a significant reduction in tumor burden after PDL treatment, with residual histologic tumor burden ranging from <1% to 29% of the original clinical tumor diameter, compared to 13-68% residual tumor burden for the corresponding controls (P-value = 0.05). CONCLUSIONS: PDL is an effective means of reducing tumor burden in patients with large BCCs and may be an alternative therapy in BCCs <1.5 cm in diameter.

TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas.

The transient receptor potential cation channel, subfamily M, member 1 (TRPM1/Melastatin-1/MLSN-1) expression has been shown to have prognostic utility in the evaluation of primary cutaneous melanoma. We analyzed a series of spindled and epithelioid cell nevi (Spitz) and primary cutaneous nodular melanomas to determine whether the expression of TRPM1 mRNA may be useful in distinguishing between Spitz nevi and nodular melanomas and to further examine the patterns of TRPM1 mRNA expression in cutaneous melanocytic proliferations. Formalin-fixed, paraffin-embedded tissues from 95 Spitz nevi and 33 nodular melanomas were analyzed for the expression of TRPM1 mRNA by in situ hybridization using (35)S-labeled riboprobes. Ubiquitous melanocytic expression of TRPM1 mRNA was observed in 56 of 95 (59%) Spitz nevi and 4 of 33 (12%) nodular melanomas. Diffusely scattered loss of TRPM1 mRNA was identified in 38 of 95 (40%) Spitz nevi and 2 of 33 (6%) nodular melanomas. Regional loss of the TRPM1 mRNA expression by a significant subset of dermal tumor cells or a complete absence of TRPM1 expression by the dermal tumor was identified in 27 of 33 (82%) nodular melanomas, but only 1 of 95 (1%) Spitz nevi. These findings suggest that the pattern of TRPM1 mRNA expression may be helpful in the differentiation of Spitz nevi and nodular melanomas. Of the 16 patients who experienced metastasis, 15 (94%) had primary tumors that displayed reduced MLSN mRNA expression by all or a part of the dermal tumor.