Pro- and anti-inflammatory cytokine gene expression in subcutaneous and visceral fat in severe obesity.

BACKGROUND AND AIMS: Pro-inflammatory molecules produced by adipose tissue have been implicated in the risk of cardiovascular (CV) disease in obesity. We investigated the expression profile of 19 pro-inflammatory and seven anti-inflammatory genes in subcutaneous adipose tissue (SAT) and in visceral adipose tissue (VAT) in 44 severely obese individuals who underwent bariatric surgery. METHODS AND RESULTS: SAT and VAT expressed an identical series of pro-inflammatory genes. Among these genes, 12 were significantly more expressed in SAT than in VAT while just one (IL18) was more expressed in VAT. The remaining genes were equally expressed. Among pro-inflammatory cytokines, both IL6 and IL8 were about 20 times more intensively expressed in SAT than in VAT. The expression of nine genes was highly associated in SAT and VAT. Only for three pro-inflammatory cytokines (IL8, IL18, SAA1) in SAT the gene expression in adipose tissue associated with the circulating levels of the corresponding gene products while no such an association was found as for VAT. CONCLUSIONS: The expression of critical pro-inflammatory genes is substantially higher in SAT than in VAT in individuals with morbid obesity. The variability in circulating levels of pro-inflammatory cytokines is, in small part and just for three pro-inflammatory cytokines, explained by underlying gene expression in SAT but not in VAT. These results point to a compartment-specific adipose tissue contribution to inflammation in obesity and indicate that abdominal SAT contributes more than VAT to the pro-inflammatory milieu associated with severe obesity.

The changing impact of age on colorectal cancer surgery. A trend analysis.

OBJECTIVE: The aim of the study was to evaluate the changing influence of age on the outcomes of colorectal cancer surgery in a retrospective trend analysis. METHODS: Data on 985 patients undergoing colorectal cancer surgery were collected during 1975-1984 and 1995-2004. Variables and outcomes of patients aged < 65, 65-74, 75-84 and 85+ years were compared with intra- and interdecade analyses. Endpoints of the study were postoperative mortality, 5-year overall and cancer-related survivals. RESULTS: The rate of elderly patients undergoing colorectal cancer surgery increased significantly from 1975-1984 to 1995-2004. Distribution of American Society of Anesthesiology score and cancer stage remained unchanged over time. The rate of palliative procedures decreased over time, most significantly in the older age groups. In 1995-2004 the palliation rate was similar across all age groups. The rate of emergency surgery also decreased, but it remained higher in older age groups. Operative mortality rate decreased over time across all age groups, but age-related differences were still observed in the 1995-2004 series. Cancer-related survival after curative surgery increased from 58% in 1975-1984 to 64% in 1995-2004 in 75+ years patients, while it increased from 56% to 78% in patients aged 74 years or younger. CONCLUSIONS: Elderly patients with colorectal cancer benefited substantially from healthcare progress during the last 30 years. The reduction of palliative procedures and the decline in operative mortality document the efficacy of not restricting the access to radical surgery for these patients.

Microsatellite instability and mismatch-repair protein expression in hereditary and sporadic colorectal carcinogenesis.

Aberrant crypt foci (ACF) are microscopic clusters of altered colonic crypts considered premalignant lesions in the large bowel. Genomic instability at short tandem repeats in the DNA, referred to as microsatellite instability (MSI) is the hallmark of hereditary nonpolyposis colorectal carcinoma (HNPCC) caused by mutations in DNA mismatch-repair genes, mostly hMLH1 and hMSH2. In this study, we evaluated for MSI ACF (n = 16), adenomas (n = 18), carcinomas (n =22), and lymph node metastases (n = 3) from 17 patients with colorectal cancer positive for MSI. Ten patients were members of HNPCC families; 7 patients had no family history of cancer. MSI was found in 7 of 7 (100%) ACF and 11 of 12 (91%) adenomas from patients with HNPCC. MSI was not related to histology and size of ACF. A progressive increase in instability as estimated by the number of shifted bands was observed along the ACF-adenoma-carcinoma sequence. In contrast, two of nine (22%) ACF and none of six adenomas from patients with MSI sporadic carcinoma were unstable at microsatellite loci. hMLH1 or hMSH2 protein expression was altered only in MSI-positive premalignant lesions (ACF and/or adenomas), but not in all MSI-positive lesions in patients with HNPCC. These observations provide evidence of the premalignant nature of ACF in HNPCC and suggest that MSI is a very early event both in HNPCC and in sporadic colorectal carcinogenesis, although in the latter it seems infrequent.

Aberrant crypt foci in the human colon: frequency and histologic patterns in patients with colorectal cancer or diverticular disease.

Aberrant crypt foci are considered potential markers of colorectal cancer risk. The aim of this study was to analyze a large series of human aberrant crypt foci according to frequency, distribution, and histology. Aberrant crypt foci were identified in methylene blue-stained colonic mucosa from 103 patients undergoing surgery for colorectal cancer or diverticular disease. Foci were histologically classified into surface hyperplastic type, surface and glandular hyperplastic type, mixed hyperplastic and adenomatous type, and adenomatous type. The mean frequency of aberrant crypt foci (n = 720) was higher in the colorectal cancer group (0.20/cm2) than in the diverticular disease group (0.07/cm2), and in distal colonic segments than in proximal segments. Most of the histologically examined foci (n = 366) were hyperplastic (88.8%). Surface hyperplasia accounted for 30.6% and prevailed in small lesions. Surface and glandular hyperplasia accounted for 58.2% and prevailed in medium-sized to large foci. Partially or totally dysplastic foci accounted for 10.1% of examined lesions (10.8% and 2.8% in the colorectal cancer and diverticular disease groups, respectively). Most of them (94.6%) were composed of mixed hyperplastic and adenomatous crypts and prevailed in large lesions. The higher frequency of aberrant crypt foci in patients with colorectal cancer sustains their putative role as preneoplastic markers. The high rate of mixed hyperplastic and adenomatous lesions supports the possible adenomatous transformation of hyperplastic lesions.

[Non-polyposis colorectal cancer in subjects under 55 years of age: frequency and phenotype of hereditary or familial syndromes]. / Il cancro non polipotico del colon e del retto sotto i 55 anni di età: frequenza e fenotipo delle sindromi a predisposizione ereditaria o familiare.

Young age is believed to be a risk factor for hereditary or familial non-polyposis colorectal cancer. Present study analysed frequency, phenotype and familial cancer risk of 82 subjects with colorectal cancer under 55 years of age. According to age and family history, probands have been subdivided into 5 groups: Hereditary Non-Polyposis Colorectal Cancer (HNPCC) (8.2% of cases); Suspected HNPCC (7.3%); Non-specific familial aggregation of colorectal cancer (AFACC) (19.5%); Early-onset colorectal cancer (diagnosis under 35 years of age) (CCG) (6.1%); Sporadic colorectal cancer (CCS) (58.5%). Proportions of probands with multiple colonic tumours were highest in HNPCC (57.1%), but present in AFACC (12.5%) and CCG (20.0%) groups, as well. Extracolonic, in particular endometrial and ovarian cancers have been found in HNPCC and AFACC probands. Tumours of proximal colon were most frequent in HNPCC, suspected HNPCC, CCG patients. Eleven-years survival rate was higher in HNPCC probands then in CCS group. Familial cancer risk in HNPCC was 3 times as much as in CCG + CCS groups. Diagnosis of colorectal cancer under 55 years of age is associated with an high frequency of hereditary or familial cases. Genetic tests, surveillance and screening programs in these patients must be based on extensive phenotype and pedigree analyses. HNPCC is widely represented in young colorectal cancer patients and is associated with a high risk of multiple synchronous or metacronous colonic and extracolonic tumours. Total colectomy and eventual hysterectomy with bilateral oophorectomy seem therefore recommendable options in these patients.

[Billiopancreatic diversion with preservation of the duodenal bulb and transitory gastroplasty in the treatment of morbid obesity. Our experience]. / La diversione bilio-pancreatica con conservazione del bulbo duodenale e gastroplastica transitoria nel trattamento dell'obesità patologica. Nostra esperienza.

We present our experience in malabsorbitive procedure in bariatric surgery based on Biliopancreatic Diversion (BPD) with transitory gastroplasty. Since 1995 we operated on 74 patients with BPD coupled with gastroplasty which is transitory due to the presence of a band in polidioxanone (PDS). The technique, proposed by Vassallo et al. in 1992, involve the respect of the duodenal bulb (5 centimeter from the pylorous) making an end-to-side duodeno-ileal isoperistaltic anastomosis. The initial excess weight loss was satisfactory (69.8% +/- 11.4% after 1 year) and it kept being stable during all the follow-up (75.2% +/- 6.4% after 5 years). The mortality was absence. We didn't observe ipoalbuminemia, diarrhea or halitosis in any patients. Only 1 patient (1.3%) developed an anastomotic ulcer. After 5 years follow-up we observed 2 cases (12.5%) of chronic hypochromic anemia and 1 case (6.2%) of hypocalcemia. We didn't perform any restorative operation. We consider this technique a good malabsortive procedure able to obtain a satisfactory and stable weight loss, with a low incidence of complications. Moreover it could be applied in patients previously treated by an ineffective gastroplasty.

Sphincter saving rectum resection is the standard procedure for low rectal cancer.

AIM: To determine the procedure of choice for rectal cancer, particularly low rectal cancer. METHODS: Complete search, according to evidence-based methods, of comparative studies and national surveys published in English since 1990. SELECTION CRITERIA: comparative studies between abdominoperineal excision (APER) and sphincter-saving operations (SSO) with a minimum of 50 patients presenting cancer in the lower one-third of the rectum, perfect split of cases with cancer located in the lower, middle or upper one-thirds of the rectum, specified numbers of patients treated by surgery alone or combined with radio-chemotherapy, specified length of follow-up with a minimum of 1 year, univariate or multivariate analysis of prognostic factors. Thirty-four studies fulfilling evidence level C were analyzed, including 6,570 patients. ENDPOINTS: operative risk, local disease control, disease free or cancer specific survival and quality of life. RESULTS: Postoperative morbidity after APER and SSO is comparable and postoperative mortality decreased to 2% or less. The type of surgery was not identified as a prognostic factor in terms of local disease control and survival. Quality of life is significantly inferior after APER. National data reveal an APER rate for cancer of the whole rectum (up to 16 cm) at 50% or above, and SSO still would represent only 32% of the radical resections for low rectal cancer. CONCLUSION: All available evidence indicates that SSO should be the procedure of choice for rectal cancer, even in the lower one-third. An APER should only be performed when cancer invades the anal sphincters and negative resection margins cannot be achieved by a SSO.

Azoxymethane-induced aberrant crypt foci and colorectal tumors in F344 rats: sequential analysis of growth.

Previous studies are consistent with the hypothesis that aberrant crypt foci (ACF) could be intermediate biomarkers in colorectal carcinogenesis. The present controlled experimental trial was performed to sequentially analyze ACF progression in rat colonic mucosa. F344 rats were administered 2-weekly doses of azoxymethane (15 mg/kg body weight, s.c.) and sacrificed 6, 12, 20, 30 and 36 weeks after the first carcinogen injection. Control groups of untreated rats were sacrificed at the same time points. The number of ACF per area, their multiplicity (number of crypts per focus), ACF frequency and multiplicity according to each colonic site, histology of ACF and macroscopic lesions were recorded. No ACF were found in control animals. In treated animals, the number of ACF per area and the multiplicity progressively and significantly increased throughout the study. ACF were prevalent in the mid colon. Lower frequencies were registered in the distal colon and rectum. ACF were rare in the proximal colon and cecum. By histology, ACF presented superficial and extensive hyperplasia. Tumors were found in the 30th and 36th week. Adenomas and well-differentiated adenocarcinomas were in the distal colon. All proximal neoplasms were signet ring cell carcinomas. In our study, ACF growing features and distribution are not correlated to adenoma and adenocarcinoma distribution. It is conceivable that signet ring cell carcinomas arising in the proximal colon, where ACF are rare, could present a different pathway of growth. The preneoplastic role of ACF and their function as intermediate biomarkers in colorectal carcinogenesis remain to be clarified.

Arthritis as a rare extra-intestinal manifestation of acute sigmoid diverticulitis.

BACKGROUND: A causal association between acute diverticulitis of the sigmoid colon and arthritis has rarely been reported. CASE REPORT: We report the case of a 60-year-old patient who developed migrating arthritis of the knee and ankle during the recurring episode of acute diverticulitis of the sigmoid colon. Treatment with NSAIDs and antibiotics had little effect on joint disease, but medical treatment was successful in reducing the diverticulitis-related symptoms. Arthritis promptly improved after surgical resection of the sigmoid colon, and 30 months later the patient is free of symptoms in the previously affected joints. CONCLUSIONS: Five cases of diverticulitis-associated arthritis have been reported. The similar case reported here reconfirms that joint disease has a limited response to medical approaches. Colon resection is recommended for patients with diverticulitis-associated arthritis which does not respond promptly to antibiotic therapy.

Inhibitory effect of a gastrin receptor antagonist, CR2945, on 1, 2-dimethylhydrazine-induced colorectal cancer in mice.

This study tested the effect of a new gastrin receptor antagonist, CR2945, on colorectal cancer induced by 1,2-dimethylhydrazine (DMH) in mice. 75 CD1 male mice were divided into 3 groups: group 1 received 1 weekly injection of 20 mg/kg of DMH and 2 daily intraperitoneal injections of 0.5 ml of NaCl 0.9% solution for 5 weeks; groups 2 and 3 received the same weekly dose of DMH and 2 daily injections of CR2945 at the respective doses of 2.5 and 7.5 mg/kg for 5 weeks. The animals were sacrificed 25 and 38 weeks after the first injection. No tumours were found at the 25th week. A lower cancer frequency (4%) was observed in treated animals compared to controls (37.4%) at the 38th week (p = 0.002). These data show that CR2945 could prevent chemically induced colon cancer development in mice.