Public cost of privately inserted laparoscopic adjustable gastric bands.

Background: Laparoscopic adjustable gastric banding (LAGB) remains a commonly performed procedure for morbid obesity. Concerns regarding its long-term consequences include high rates of band removal from complications and failure to lose weight. Many private practices continue to perform LAGB but, owing to short follow-up periods, the burden of surgical complications falls upon National Health Service (NHS) bariatric units. This study aimed to review the NHS treatment of patients for complications related to privately performed LAGB. Methods: All surgical complications following bariatric surgery referred to the Welsh Institute of Metabolic and Obesity Surgery (WIMOS) between September 2010 and September 2014 were reviewed. Type of complication, procedures performed, and number of outpatient attendances and inpatient stays were recorded. Costs of treatment were estimated using standard tariffs. Results: A total of 78 patients presented with complications after privately performed bariatric surgery. Sixty had undergone LAGB; the remainder had had other bariatric procedures. Median age was 45 (range 22-78) years, and 65 (83 per cent) were women. Urgent band deflation was undertaken in 53 patients. Band removal surgery was required in 32 patients; one patient needed a subtotal gastrectomy. There was a total of 123 outpatient/ward attendances and 340 days of inpatient care, including 10 days of intensive care. The estimated total cost to the NHS of managing these patients was €337 400 (€84 350 per annum). Conclusion: The cost burden to the NHS of managing the complications of bariatric surgery performed in the private sector is considerable. Although it is imperative that such complications be managed in well equipped specialist units, private surgery providers should have better follow-up plans and/or contractual agreements with the NHS.

Acyl-ghrelin mediated lipid retention and inflammation in obesity-related Type 2 diabetes.

Acyl-ghrelin has various peripheral effects including the potential role in mediating cellular lipid removal and macrophage polarization. Previous reports are contradictory as to how glycaemia and acyl-ghrelin mediates lipid retention and inflammation within individuals with Type 2 diabetes (T2D). Our aim was to explore acyl-ghrelin levels and ghrelin expression in relation to lipid and inflammatory markers within an ex vivo human model, biopsied visceral adipose tissue. Results indicated that acyl-ghrelin was associated with a decline in key lipid homeostasis genes ABCG1 and LXRß expression. Within T2D there was also a down regulation of these genes which was independent of acyl-ghrelin levels. Circulatory pro-inflammatory markers (IL-6 and TNFα) had no association with ghrelin expression nor circulating acyl-ghrelin levels. Anti-inflammatory marker (IL-10) and total antioxidant status (TAOS%) were positively associated with ghrelin expression across samples from all groups combined (total sample cohort) and specifically within the obesity sample cohorts. Data supported the hypothesis that hyperglycaemia and acyl-ghrelin have a regulatory role in lipid retention. Furthermore, that both acyl- and desacyl-ghrelin is responsible for a protective inflammatory response; however this response is diminished in T2D.

Changes in markers of oxidative stress and DNA damage in human visceral adipose tissue from subjects with obesity and type 2 diabetes.

AIMS: In the past 30 years, prevalence of obesity has almost trebled resulting in an increased incidence of type 2 diabetes mellitus and other co-morbidities. Visceral adipose tissue is believed to play a vital role, but underlying mechanisms remain unclear. Our aim was to investigate changes in markers of oxidative damage in human visceral adipose tissue to determine levels of oxidative burden that may be attributed to obesity and/or diabetes. METHODS: Visceral adipose tissue samples from 61 subjects undergoing abdominal surgery grouped as lean, obese and obese with type 2 diabetes mellitus, were examined using 3 different markers of oxidative stress. Malondialdehyde (MDA) concentration was measured as a marker of lipid peroxidation, telomere length and Comet assay as markers of oxidative DNA damage. RESULTS: No significant difference in MDA concentration, telomere length and DNA damage was observed between groups, although longer telomere lengths were seen in the obese with diabetes group compared to the obese group (P<0.05). Lower MDA concentration and longer telomere length were seen in subjects with diabetes compared to those without (P<0.05). DNA damage, analysed via Comet assay, was significantly lower in subjects with diabetes compared to those without (P<0.05). CONCLUSION: A paradoxical decrease in oxidative stress and DNA damage was observed in samples from subjects with type 2 diabetes mellitus. Further work is required to investigate this further, however this phenomenon may be due to an up regulation of antioxidant defences in adipose tissue.

Immunohistochemical study of nuclear factor-kappaB activity and interleukin-8 abundance in oesophageal adenocarcinoma; a useful strategy for monitoring these biomarkers.

AIMS: To determine if immunohistochemistry (IHC) could be used to monitor nuclear factor-kappaB (NF-kappaB) activity in oesophageal adenocarcinoma and pre-malignant (Barrett's) oesophageal tissues, relative to normal oesophageal mucosa. The pro-inflammatory cytokine interleukin-8 (IL-8), a transcriptional target of NF-kappaB, was also studied to better understand NF-kappaB functionality; its RNA and protein levels were assessed in oesophageal tissues. METHODS: IHC was employed using an antibody against the nuclear localisation sequence (NLS) of the p65 subunit as well as an antibody against IL-8. To assess NF-kappaB function, changes in gene expression of NF-kappaB controlled genes (IL-8 and I-kappaB) were also assessed in the histological sequence using real-time PCR. More global expression changes were also studied using membrane arrays. RESULTS: IHC was effective at monitoring overall NF-kappaB activity and IL-8 abundance. This method also allowed NF-kappaB activity and IL-8 abundance to be pinpointed in specific cell types. There were significant increases in nuclear NF-kappaB activity and IL-8 abundance across the histological series. Gene expression analysis also showed consistent up-regulation of IL-8, confirming the IHC data and showing enhanced transcriptional NF-kappaB activity. I-kappaB (another NF-kappaB target) showed down-regulation in dysplastic and adenocarcinoma tissues. Down-regulation of I-kappaB gene expression may partly explain increased NF-kappaB activity. CONCLUSION: IHC, using antibodies against the NLS of p65, may be useful in monitoring overall NF-kappaB activity in oesophageal tissues. As IHC is amenable to high-throughput screening (whereas traditional electrophoretic mobility shift assay methods are not), this may lead to the development of a better screening tool for early cancer risk.

[Insemination: history and state of the art in animals]. / L'insémination: historique, état des lieux chez l'animal.

Insemination has been used since 1950 in the bovine and since the seventies in other domestic species. The use of insemination varies between the different species in terms of activity and method. The methods depend on the anatomical and physiological characteristics of each species, which lead to different sites of semen deposition and different minimal numbers of inseminated spermatozoa to obtain efficient fertility results. The use of frozen semen influences also the methods of insemination. Intra-uterine insemination is principally used when only small quantities of semen are available and/or to reduce the number of inseminated spermatozoa. Recent results in different species indicate that the use of intra-uterine insemination could be developed in the next years.

Treatment of postoperative peritonitis of small-bowel origin with continuous enteral nutrition and succus entericus reinfusion.

HYPOTHESIS: Proximal intestinal stomas established by the exteriorization of leaking anastomosis in the presence of peritonitis can be used to reinfuse succus entericus and provide adequate enteral nutrition. DESIGN: Retrospective analysis of prospectively gathered data from a cohort of consecutive patients admitted between January 1993 and December 1999 for postoperative peritonitis requiring laparotomy and the construction of one or more small-bowel stomas. SETTING: Tertiary referral center with a surgical intensive care unit experienced in the treatment of intra-abdominal sepsis and succus entericus reinfusion. PATIENTS: Twenty-one consecutive patients with postoperative peritonitis originating from a jejunal or ileal leak. We excluded patients with established enterocutaneous fistulae, abscesses amenable to percutaneous drainage or other conservative treatments, and postoperative peritonitis caused by ileocolic or ileorectal anastomosis. INTERVENTIONS: Early laparotomy with exteriorization of small-bowel leak(s), and continuous enteral nutrition (CEN) and succus entericus reinfusion (SER) via the distal portion of the stoma until gastrointestinal continuity was restored. MAIN OUTCOME MEASURES: Feasibility of CEN and SER with temporary, diverting small-bowel stomas and their associated postoperative morbidity and mortality rates. RESULTS: One patient died, and 14 experienced complications. For technical reasons, CEN and SER were discontinued early on in 7 patients. The mean duration of CEN and SER was 58 days and 61 days, respectively. Enteral feedings allowed the suppression of central venous access after a median of 28 days, with 82 days as a median time to restoration of intestinal continuity. CONCLUSIONS: Although the exteriorization of small-bowel leaks with CEN and SER is generally feasible and effective in the treatment of critically ill patients with peritonitis secondary to small-bowel leaks, it is associated with significant morbidity and mortality, in part relating to patients' underlying diseases.

Results of reoperations in colorectal anastomotic strictures.

PURPOSE: The incidence of colorectal anastomotic strictures varies from 3 to 30 percent. Most of these anastomotic strictures are simple narrowings shorter than 1 cm that can be successfully treated by dilation or endoscopic alternatives. However, up to 28 percent of patients will require surgical correction. This can be technically difficult, with the possibility of a permanent colostomy. This study reports the outcomes after operative treatment of severe strictures of colorectal anastomoses. METHODS: From August 1992 to October 1996, 27 patients were referred for surgical treatment of severe rectal anastomotic strictures. The reasons for the initial surgery were as follows: rectal cancer (13), diverticular disease (7), Hirschsprung's disease (2), rectal endometriosis (2), uterine carcinoma with rectal invasion (1), ruptured abdominal aortic aneurysm with rectosigmoid necrosis (1), and rectovaginal fistula (1). There were 15 (56 percent) stapled anastomoses, and 21 (78 percent) patients had developed a postoperative leak. RESULTS: The median time between initial surgery and diagnosis of the stenosis was 7.2 (range, 1-24) months and between the last operation and referral was 15.1 (range, 1-44) months. Stenosis was located at a mean distance of 9.5 (range, 4-15) cm from the anal verge. Eleven patients (41 percent) had been unsuccessfully dilated before referral. Surgical correction of the stenosis required 7 colorectal anastomoses for upper rectal anastomotic strictures and 20 coloanal anastomoses for middle and lower rectal strictures (19 Soave's procedures and 1 colon J-pouch-anal anastomosis). Intestinal continuity was restored in all cases. After a mean follow-up of 28.7 +/- 14 months, no recurrences were detected and functional results were satisfactory. CONCLUSIONS: Resection of the stenosis and construction of a new colorectal anastomosis can be performed successfully for upper rectal anastomotic stricture. For a stenosis located in the middle and lower rectum, Soave's procedure offers a good alternative, with satisfactory long-term functional results. Whichever technique is used, a permanent colostomy should rarely be required.

Prognosis in Duke's B colorectal carcinoma: the Jass classification revisited.

OBJECTIVE: To assess whether Jass staging enhances prognostic prediction in Dukes' B colorectal carcinoma. DESIGN: A historical cohort observational study. SETTING: A university tertiary care centre, Switzerland. SUBJECTS: 108 consecutive patients. INTERVENTIONS: Curative resection of Dukes' B colorectal carcinoma between January 1985 and December 1988, Patients with familial adenomatous polyposis; hereditary non-polyposis colorectal cancer; Crohns' disease; ulcerative colitis and synchronous and recurrent tumours were excluded. A comparable group of 155 consecutive patients with Dukes' C carcinoma were included for reference purposes. MAIN OUTCOME MEASURES: Disease free and overall survival for Dukes' B and overall survival for Dukes' C tumours. RESULTS: Dukes' B tumours in Jass group III or with an infiltrated margin had a significantly worse disease-free survival (p = 0.001 and 0.0001, respectively) and those with infiltrated margins had a significantly worse overall survival (p = 0.002). Overall survival among those with Dukes' B Jass III and Dukes' B with infiltrated margins was no better than overall survival among all patients with Dukes' C tumours. CONCLUSION: Jass staging and the nature of the margin of invasion allow patients undergoing curative surgery for Dukes' B colorectal carcinoma to be separated into prognostic groups. A group of patients with Dukes' B tumours whose prognosis is inseparable from those with Dukes' C tumours can be identified, the nature of the margin of invasion being used to classify a larger number of patients.

Prognostic factors in colorectal cancer.

Prognosis of patients after colorectal cancer resection is predominantly influenced by the extent of local tumour growth and the presence or absence of nodal or distant metastasis. However, many factors have been used to generate numerous classification systems, leading to some debate and confusion. The effects on survival of 7 clinical and pathological parameters were reviewed in 801 consecutive patients operated upon with locally curative intent for colorectal cancer over a ten-year period. Age less than 50 or more than 70 years, poor cellular differentiation, high mucous secretion by tumour cells and Dukes' staging were the parameters significantly correlated to poor overall survival (p<0.001 for each). The Cox's regression analysis identified the same parameters as independent prognostic factors. The value of age as a prognostic factor remains debatable, but the other three parameters must be considered when evaluating prognosis after curative surgery for colorectal cancer and when considering adjuvant therapy.

For patients with Dukes' B (TNM Stage II) colorectal carcinoma, examination of six or fewer lymph nodes is related to poor prognosis.

BACKGROUND: Lymph node status is pivotal to the staging of colorectal carcinoma. The diagnosis of a lymph node negative tumor should imply a good prognosis; however, the outcomes for Dukes' B (TNM Stage II) patients remain variable, possibly in part due to understaging. The aim of this study was to determine whether examining a specified minimum number of lymph nodes using conventional techniques would eliminate the risk of understaging and thus have an effect on prognosis. METHODS: Data on patients who underwent surgery for colorectal carcinoma at a single institution between 1985 and 1990 were reviewed. Patients with Dukes' B (TNM Stage II) or C (TNM Stage III) tumors and histologically confirmed disease-free resection margins who were treated with curative intent were included. Correlations among variables were assessed using the chi-square test, and survival comparisons were made using Kaplan-Meier curves and the log rank test. Multivariate analysis was performed using a Cox regression model. RESULTS: Dukes' B (TNM Stage II) patients with < or =6 lymph nodes examined had significantly poorer overall survival than those with > or =7 lymph nodes examined (P = 0.0014). Such a significant difference was not observed among Dukes' C (TNM Stage III) patients (P = 0.7). Survival of Dukes' C patients was significantly worse compared with that of Dukes' B patients overall and Dukes' B patients with > or =7 lymph nodes examined (P < 0.0001). There was no significant difference in survival between Dukes' C and Dukes' B patients with < or =6 lymph nodes examined (P = 0.02). The number of examined lymph nodes was the only significant parameter correlated with survival in the multivariate analysis (P = 0.002). CONCLUSIONS: Because Dukes' B patients with < or =6 examined lymph nodes have poorer outcomes than those with a higher number examined (probably due to understaging), the total number of examined lymph nodes should always be reported.

The type of K-ras mutation determines prognosis in colorectal cancer.

BACKGROUND: Mutations involving the oncogene K-ras in colorectal cancer may be related to tumor aggressiveness. However, the value of K-ras gene determination as a prognostic marker has not been clearly established. PATIENTS AND METHODS: The results from 98 patients recruited in a prospective study analyzing the effect of a K-ras mutation as a prognostic factor in colorectal cancer are reported. RESULTS: Disease-free (P = 0.02) and overall survival (P = 0.03) were significantly reduced for patients harboring a K-ras mutation. Two specific mutations demonstrated a significantly increased risk of disease recurrence, namely, 12-TGT (P = 0.04) and 13-GAC substitutions (P = 0.002). Patients with either of these substitutions had a 2-year disease-free survival rate of 37% compared with that of 67% for the group of patients harboring any other mutation type or a wild-type status (P = 0.01). CONCLUSIONS: The results herein presented suggest that K-ras acts as a prognostic factor in colorectal cancer and that this effect is probably related to a limited number of defined mutations.

[A comparative study on p53 gene mutation in primary human Dukes C colon cancer with that in matched lymph node metastasis].

OBJECTIVE: To study the relationship between metastasis of colon cancer and the mutation of p53 gene. METHODS: PCR-SSCP was used to analyse exon 5-9 of the p53 gene in 73 cases of Dukes C human primary cancer and 40 cases of matched lymph node metastasis. RESULTS: Mutations were identified in 27 of 73 primary cancers (37%) and 19 of 40 lymph node metastasis (47.5%) with the overall incidence of p53 mutation being 44%. In 21 of 40 cases in which both primary and metastatic cancers were analysed by SSCP, we found no p53 mutations in both lesions. While the same exon and exactly the same mutated band pattern could be seen both in primary and metastatic cancers in another 12 cases (30%). In addition, the agreement of p53 mutation status in primary cancer to the lymph node metastases was lost in the remaining 7 cases (17.5%). All of the 7 cases were confirmed to have base substitution mutations by DNA direct sequencing. In 5 of 7 individuals, the point mutations were detected only in lymph node metastases but not in the primary cancers and in 2 of 7 cases, two exons were found to have mutations in lymph node metastases while only one or no mutation was identified in the primary cancers. CONCLUSION: Most p53 mutations occurred before metastasis and p53 mutations persist throughout the final stage of the progression and metastasis in colon cancer. Furthermore, the metastasis of colon cancer is accompanied by the emergence of new mutation in p53 gene or metastasis is selected against the p53 mutation, which suggests that the mutations in p53 gene may be related to the metastasis of colon cancer.

Genetic diversity at the p53 locus between primary human colorectal adenocarcinomas and their lymph-node metastases.

In both the primary tumor and associated lymph-node metastases of 40 cases of Dukes' C colorectal adenocarcinomas, exons 5 to 9 of the p53 tumor-suppressor gene were examined by PCR amplification and single-strand-conformation-polymorphism(SSCP) analysis. Mobility shifts indicating p53 mutations, which were confirmed by direct sequencing, were identified in 14 primary cancers (35%) and in 19 of the 40 lymph-node metastases (48%). In 12 cases (30%), the p53-mutation status in the primary cancer and its lymph-node metastases was identical. This result is compatible with the hypothesis that when a p53 mutation occurs before the establishment of lymph-node metastasis, it subsequently persists in the metastatic nodes. In 7 cases (18%), p53 mutations were identified in lymph-node metastases that were not concordant with the p53 status in the primary tumor. This finding can be explained by assuming that (1) p53 heterogeneity existing in the primary tumor is not reflected in all metastases and/or (2) new p53 mutations may occur during the development of metastatic lesions.

[Hereditary nonpolyposis colorectal cancers]. / Le cancer colorectal héréditaire non polyposique.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal, dominantly inherited disease leading to a marked increase in cancer susceptibility, notably colorectal cancer, affecting up to one in 400 individuals in the Western world. Four genes responsible for the majority of cases have been identified. Colorectal cancer in affected people tends to be right sided, occur at an earlier age, and there is a propensity for synchronous or metachronous lesions. Extra-colonic tumours may occur with an elevated frequency, most importantly cancer of the endometrium, but also stomach, hepatobiliary system, small bowel, proximal ureter and renal pelvis, and ovary. On account of these features, management guidelines for members of HNPCC kindreds require modification from those generally advised for patients with sporadic tumours. The cardinal feature for the identification of affected families is the family history. All clinicians have a duty to identify such patients under their care as appropriate screening and surgery should lead to an improved prognosis for such patients and their families.

[Familial adenomatous polyposis]. / La polypose adénomateuse familiale.

Familial adenomatous polyposis (FAP) is an autosomal dominant disease characterized by the development of numerous adenomatous polyps in the colon and rectum with diverse extracolonic manifestations. Recent genetic advances have lead to the sequencing of the FAP gene, with important implications for screening, diagnosis and follow-up. Appropriate management of probands and at-risk patients is of the utmost importance, as untreated carriers will develop colorectal cancer. Identification of FAP families and tracing of pedigrees represent the most important steps. To this end registries are essential, allowing a comprehensive multidisciplinary approach. They have justified their place by decreasing related morbidity and mortality. An overview and discussion of clinical features and management are presented.

Distribution of an Indoleacetic Acid-oxidase-inhibitor in the Storage Root of Daucus carota.

Indoleacetic acid (IAA)-oxidase from both secondary phloem and xylem was dependent on 2,4-dichlorophenol for activity, and was enhanced by addition of Mn(2+). The pH optimum was 6.0 from both tissues. IAA-oxidase and its inhibitors were distributed differently in the secondary phloem and secondary xylem of carrot root. In the phloem a high IAA-oxidase activity was distributed uniformly along the radius but in the xylem a somewhat lower concentration decreased from the cambium. IAA-oxidase inhibitor in the phloem increased exponentially from a very low concentration near the cambium, whereas in the xylem an appreciable concentration was present near the cambium, decreasing linearly with distance from the cambium. Longitudinal gradients in the xylem parallel studies by other workers with the greatest IAA-destroying capacity present in older tissues. In the xylem inhibitor decreased and IAA-oxidase increased from the root apex. In the phloem IAA-oxidase was uniform, whereas the inhibitor increased in older tissue.The IAA-oxidase inhibitors in phloem and xylem may be different. In the xylem the IAA-oxidase inhibitor may be a lignin precursor present in young cells which disappears as lignification proceeds. In the phloem IAA-oxidase reacting with endogenous IAA appears to form a physiologically active product.