'Prechronous' metastasis in clear cell renal cell carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although metastatic carcinoma in the presence of an occult primary tumor is well recognized, underlying reasons for the failure of the primary tumor to manifest are uncertain. Explanations for this phenomenon have ranged from spontaneous regression of the primary tumor to early metastasis of the primary tumor before manifestation of a less aggressive primary tumor. We report a case of 'prechronous' metastasis arising from clear cell renal cell carcinoma, where metastatic disease initially manifested in the absence of a primary renal tumor, followed by aggressive growth of the primary renal lesion.</p> <p>Case presentation</p> <p>A 43-year-old Malay man initially presented to our facility with fever and cough. He subsequently underwent surgical resection of a 9 cm right-sided lung mass found on radiological examination. Histology showed a high-grade clear cell tumor with sarcomatoid differentiation, suggestive of a metastasis from clear cell renal cell carcinoma. However, no concurrent renal lesions were noted on computed tomographic evaluation at that time. Then, four months after lung resection, he presented with a subcutaneous mass in the left loin, as well as right loin discomfort. Computed tomography scanning revealed a 10 cm right renal mass, with renal vein and inferior vena cava invasion, as well as recurrent disease in the right thorax. Histological examination of the excised subcutaneous mass revealed a high-grade carcinoma consistent with clear cell renal cell carcinoma.</p> <p>Conclusions</p> <p>This is the first reported case of prechronous metastasis of renal cell carcinoma, with metastatic disease manifesting prior to the development of the primary lesion. The underlying mechanism is uncertain, but our patient's case provides anecdotal support for the early dissemination model of metastasis.</p

Rapamycin and Thalidomide Treatment of a Patient with Refractory Metastatic Gastroesophageal Adenocarcinoma: A Case Report

The use of rapamycin and thalidomide in a patient with metastatic gastroesophageal carcinoma, which led to disease stability associated with a significant tumor marker response and improved clinical quality of life, is reported

Potentially Functional SNPs (pfSNPs) as Novel Genomic Predictors of 5-FU Response in Metastatic Colorectal Cancer Patients

<div><p>5-Fluorouracil (5-FU) and its pro-drug Capecitabine have been widely used in treating colorectal cancer. However, not all patients will respond to the drug, hence there is a need to develop reliable early predictive biomarkers for 5-FU response. Here, we report a novel potentially functional Single Nucleotide Polymorphism (pfSNP) approach to identify SNPs that may serve as predictive biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC) patients. 1547 pfSNPs and one variable number tandem repeat (VNTR) in 139 genes in 5-FU drug (both PK and PD pathway) and colorectal cancer disease pathways were examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by RECIST criteria was used as the clinical end point. Four non-responder-specific pfSNPs were found to account for 37.5% of all non-responders (P<0.0003). Five additional pfSNPs were identified from a multivariate model (AUC under ROC = 0.875) that was applied for all other pfSNPs, excluding the non-responder-specific pfSNPs. These pfSNPs, which can differentiate the other non-responders from responders, mainly reside in tumor suppressor genes or genes implicated in colorectal cancer risk. Hence, a total of 9 novel SNPs with potential functional significance may be able to distinguish non-responders from responders to 5-FU. These pfSNPs may be useful biomarkers for predicting response to 5-FU.</p></div

List of SNPs with non-responder specific allele in both groups.

<p>Abbreviations: Reported: previously reported in the literature to be associated with disease/function; ESE/ESS: change Exon splice enhancer/silencer; NMD: mRNA nonsense mediated decay; Non-syn: non-synonymous SNP; ProteinDomain: residing in important protein domains; miRNA: change miRNA binding site; RPS: show signature of recent positive selection; TF: change transcription factor binding site; ISRE: change intron splice regulatory element; DelAA: Deleterious amino acid change; CodonDiff: High codon usage difference.</p><p>List of SNPs with non-responder specific allele in both groups.</p

The demographic characteristics of the patients recruited for each study.

<p>The demographic characteristics of the patients recruited for each study.</p

The molecular functions of the three SNPs in UMPS gene with minor allele uniquely found in non-responders are all linked to disabling UMPS.

<p>The molecular functions of the three SNPs in UMPS gene with minor allele uniquely found in non-responders are all linked to disabling UMPS.</p

The ROC curve for the logistic regression based multivariate model trained to differentiate non-responders who do not have the non-responder.

<p>The AUC of the ROC curve is 0.875. The point of maximum sum of sensitivity and specificity is highlighted by the green circle on the ROC curve. The corresponding sensitivity and specificity is 62.5% and 100% respectively.</p

The list of less-common SNPs with non-responder specific allele and their predicted molecular functions.

<p>The list of less-common SNPs with non-responder specific allele and their predicted molecular functions.</p

List of SNPs showing P<0.05 in Group 1 ranked by P value.

<p>Abbreviations: Reported: previously reported in the literature to be associated with disease/function; ESE/ESS: change Exon splice enhancer/silencer; NMD: mRNA nonsense mediated decay; Non-syn: non-synonymous SNP; ProteinDomain: residing in important protein domains; miRNA: change miRNA binding site; RPS: show signature of recent positive selection; TF: change transcription factor binding site; ISRE: change intron splice regulatory element.</p><p>List of SNPs showing P<0.05 in Group 1 ranked by P value.</p