ADIPOQ rs266729 G/C gene polymorphism and plasmatic adipocytokines connect metabolic syndrome to colorectal cancer.

Background: ADIPOQ gene, which encode for Adiponectin (APN), is sited on chromosome 3q27 and linked to a susceptibility locus for metabolic syndrome (MetS). The ADIPOQ rs266729 G/C gene polymorphism is significantly associated with low APN levels and linked to susceptibility to develop cancer. In addition, decreased APN serum levels are linked with tumor development and progression and inversely associated with markers of inflammation. Here, we investigate the influence of APN rs266729 G/C polymorphism on adipocytokine circulating levels and their association with MetS in colorectal cancer patients (CRC). Methods: Blood samples from 105 CRC patients (50 women and 55 men) with and without MetS were genotyped for APN rs266729 G/C polymorphism by TETRA ARMS PCR. ELISA assay was used to measure plasma levels of APN and inflammatory TNF-α cytokine. Biochemical and anthropometric parameters of MetS were also analyzed. Results: We found that CRC patients (N=75) with genotype rs266729G/C or carriers of G allele were associated with a significantly increased risk of MetS development (OR =2.9) compared to those with CC genotype (N=30). Also, CG/GG genotypes were associated with significantly lower plasma APN levels and higher TNF-α levels in comparison to CC genotype (P=0.034) and APN levels were decreased in relation to BMI increases (P=0.001). Conclusions: Our findings show that APN rs266729 G/C polymorphism is associated with lower APN levels in CRC patients, indicating that decreased circulating levels of APN may be a determinant risk factor for CRC in MetS patients.

Comparison of (18)F-FDG PET/CT methods of analysis for predicting response to neoadjuvant chemoradiation therapy in patients with locally advanced low rectal cancer.

PURPOSE: The aim of this study was to prospectively investigate the predictive value of (18)F-FDG PET/CT semiquantitative parameters for locally advanced low rectal cancer (LARC) treated by neoadjuvant chemoradiation therapy (nCRT). METHODS: 68 patients with LARC had (18)F-FDG PET/CT scans twice (baseline and 5-6 weeks post-nCRT). All patients underwent surgery with preservation of the sphincter 8 weeks later. (18)F-FDG PET/CT analysis was performed by visual response assessment (VRA) and semiquantitative parameters: SUVmax(baseline), SUVmean(baseline), MTV(baseline), TLG(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), TLG(post-nCRT); ΔSUVmax and mean and Response indexes (RImax% and RImean%). Assessment of nCRT tumor response was performed according to the Mandard's Tumor Regression Grade (TRG) and (y)pTNM staging on the surgical specimens. Concordances of VRA with TRG, and with (y)pTNM criteria were evaluated by Cohen's K. Results were compared by t student test for unpaired groups. ROC curve analysis was performed. RESULTS: VRA analysis of post-nCRT (18)F-FDG PET/CT scan for the (y)pTNM outcome showed sensitivity, specificity, accuracy, PPV, and NPV of 87.5%, 66.7%, 83.8%, 92.5%, and 53.3%, respectively. Concordances of VRA with TRG and with (y)pTNM were moderate. For the outcome variable TRG, the statistical difference between responders and non-responders was significant for SUVmax(post-nCRT) and RImean%; for the outcome variable (y)pTNM, there was a significant difference for MTV(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. ROC analysis showed better AUCs: for the outcome variable TRG for SUVmax(post-nCRT), SUVmean(post-nCRT), and RImean%; for the outcome variable (y)pTNM for MTVbaseline, SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. No significant differences among parameters were found. CONCLUSIONS: Qualitative and semiquantitative evaluations for (18)F-FDG PET/CT are the optimal approach; a valid parameter for response prediction has still to be established.

Prospective analysis of 18F-FDG PET/CT predictive value in patients with low rectal cancer treated with neoadjuvant chemoradiotherapy and conservative surgery.

UNLABELLED: This study prospectively assessed (18)F-FDG PET/CT in predicting the response of locally advanced low rectal cancer (LRC) to neoadjuvant chemoradiation (nCRT). METHODS: 56 patients treated with chemoradiation underwent two (18)F-FDG PET/CT scans (baseline and 5-6 weeks post-nCRT). (18)F-FDG uptake (SUVmax and SUVmean) and differences between baseline (SUV1) and post-nCRT (SUV2) scans (ΔSUV and RI%) were evaluated. Results were related to the Mandard's TRG and (y)pTNM. RESULTS: (18)F-FDG PET/CT sensitivity, specificity, accuracy, PPV and NPV resulted in 88.6%, 66.7%, 83.92%, 90.7%, and 61.5%. SUV2 resulted in better than SUV1 to predict nCRT response by TRG, with no significant statistical difference between the SUVmax2 and SUVmean2 AUC (0.737 versus 0.736; P = 0.928). The same applies to the (y)pTNM (0.798 versus 0.782; P = 0.192). In relation to the TRG, RI values had a higher AUC than ΔSUV, with no significant difference between RImax and RImean (0.672 versus 0.695; P = 0.292). The same applied to the (y)pTNM (0.742 versus 0.741; P = 0.940). In both cases ΔSUV does not appear to be a good predictive tool. Logistic regression confirmed the better predictive role of SUVmax2 for the (y)pTNM (odds ratio = 1.58) and SUVmean2 for the TRG (odds ratio = 1.87). CONCLUSIONS: (18)F-FDG PET/CT can evaluate response to nCRT in LRC, even if more studies are required to define the most significant parameter for predicting pathologic tumor changes.

Co-expression of CD133(+)/CD44(+) in human colon cancer and liver metastasis.

Although relatively good therapeutic results are achieved in non-advanced cancer, the prognosis of the advanced colon cancer still remains poor, dependent on local or distant recurrence of the disease. One of the factors responsible for recurrence is supposed to be cancer stem cells (CSCs) or tumor-initiating cells, which are a population of cancer cells with ability to perpetuate themselves through self-renewal and to generate differentiated cells, thought to be responsible for tumor recurrence. This study globally approach the possible role of tissue-derived stem cells in the initiation of colon cancer and its metastatic process in the liver. Fresh surgical specimens from colon cancer, non-tumor tissue and liver metastasis were obtained directly from the operating room, examined, and immediately processed. CSCs were selected under serum-free conditions and characterized by CD44 and CD133 expression levels. CD133(+)/CD44(+) cell populations were then investigated in paraffin-embedded tissues and circulating tumor cells isolated from peripheral blood of the same group of colon cancer patients. Our data demonstrate that metastatic properties of cell populations from blood and liver metastasis, differently from primitive tumors, seem to be strictly related to the phenotype CD133 positive and CD44 positive.

Transanal tube NO COIL® after rectal cancer proctectomy. The "G. Paolo II" Cancer Centre experience.

AIMS AND BACKGROUND: Covering stoma is the main method used to protect low-lying anastomosis after cancer proctectomy. Intraluminal rectal pressure could be a potential risk factor for anastomotic leakage. We present our personal experience with an alternative and original device, the transanal tube NO COIL®, evaluating its feasibility and safety based on a preliminary manometric study. METHODS: From May 1998 to March 1999, an experimental manometric study on 35 subjects was performed to assess the pathophysiological basis of intraluminal rectal pressure with or without the transanal tube. Subsequently, from April 1999 to December 2009, 184 patients (107 males, 77 females, average age 68.2 ± 10 years) with primary adenocarcinoma of the rectum (≤12 cm from anal verge) were selected. Eighty-two underwent total proctectomy and 102 subtotal proctectomy. No stoma were fashioned. At the end of the operation, the silicone transanal tube NO COIL ®, 60-80 mm long, 2 mm thick with a calibre of up to 2 cm, was applied and secured to the perineal skin by two stitches, then removed on the seventh postoperative day if no signs of leakage occurred. RESULTS: The intraluminal rectal pressure with transanal tube was strongly reduced from 13.8 + 8.5 mmHg to 4.8 + 3.7 mmHg (P <0.01). Nine patients (4.8%) developed an anastomotic leakage, 2 males and 7 females. In 10 patients, the transanal tube NO COIL® did not remain in situ for the planned seven days, and 18 patients suffered from ulcers in the perianal skin. Leakage subsided with conservative treatment in 4 patients, whereas 5 patients required loop colostomy. The stoma rate was 2.7%. No leakage-related deaths occurred, and overall mortality was 1.3%. CONCLUSIONS: The transanal tube NO COIL® does not abolish the risk of anastomotic leakage but could be an alternative option to covering stoma after cancer proctectomy in selected patients. In our experience, this simple and cheap device could reduce the rate of stoma without leakage-related mortality. Further studies within a randomized controlled trial are required to better define our results.

Isolated splenic metastasis from colon cancer. Report of a case.

Isolated splenic metastasis is an uncommon event, except in the case of secondary involvement by lymphoma. The most common sites of metastases of colorectal cancer are the regional lymph nodes, liver and peritoneum; lung and bone are rarely involved, the spleen exceptionally. In this paper we report a case of metachronous isolated splenic metastasis of transverse colon cancer in an 80-year-old woman who was successfully treated by splenectomy. The peculiar clinical-pathological aspects of this kind of metastasis are discussed on the basis of our clinical observation and a review is presented of similar cases reported in the literature. Only 14 reported cases of isolated splenic metastasis from colorectal cancer were found in Medline.