Pancreatoduodenectomy for suspected malignancy: nonmalignant histology confers increased risk of serious morbidity.

BACKGROUND/AIMS: A tissue diagnosis is not always obtained prior to pancreatoduodenectomy (PD) and a proportion of patients are found to have noncancerous histology postoperatively. It is unknown if these patients have different outcomes when compared with those who have malignancy confirmed. METHODS: A retrospective paired case matched control study was undertaken. Patients who underwent PD for suspected malignancy but ultimately had nonmalignant histology were identified. Each was matched to a confirmed malignant control using the following criteria: age, gender, body mass index, American Society of Anesthesiologists grade, neoadjuvant treatment, preoperative serum bilirubin, preoperative biliary stenting and type of pancreatic anastomosis. Matching was blinded to the measured outcomes, which included perioperative morbidity and mortality. RESULTS: Forty-five cases were compared with 45 well-matched controls. There was no difference in 30- or 90-day mortality, or length of stay. While overall morbidity rates were the same, patients with nonmalignant disease were more likely to experience major (Clavien-Dindo grade III-IV) morbidity (40.0% versus 17.8%, p = 0.0352). Independently, rates of clinically relevant pancreatic fistula (CR-POPF) were higher in the nonmalignant group (22.2% versus 4.44%, p = 0.0131). CONCLUSIONS: In our study, PD patients with nonmalignant histology had significantly higher incidence of major morbidity and CR-POPF when compared with those who had malignancy confirmed. This should be considered when planning the management of patients with known or presumed benign/premalignant disease.

Immunohistochemical localization of cadherin and catenin adhesion molecules in the murine growth plate.

Mouse tibial growth plates were examined for the presence of adhesion molecules using immunohistochemistry and RT-PCR. All of the components of the classical cadherin/catenin complex (cadherin, alpha-, beta-, and gamma-catenin), as well as a heavy presence of p120, were identified in the murine growth plate. All of the major cadherins (1-5, 11, 13, and 15) were, for the first time, identified and localized in the murine growth plate. We have demonstrated that most of the cadherins and catenins reside in the zone of hypertrophy. Only alpha-catenin and E-, P-, R-, and VE-cadherin were found in all regions of the growth plate. The results for T-cadherin were inconclusive.

Ischemia-induced cleavage of cadherins in NRK cells is not sufficient for beta-catenin transcriptional activity.

Although ischemia is associated with disruption of cadherin-mediated adhesion in renal cell lines, the impact of decreased cadherin function on the transcriptional activity of beta-catenin remains poorly defined. In these studies, we used a simulated ischemia model in normal rat kidney (NRK) cells to disrupt cadherin function. Cell viability; cadherin/catenin expression, function, and localization; and beta-catenin-mediated transcriptional activity were assessed during ischemia/reperfusion. Following 6 hr of ischemia, a decrease in the expression of E- and N-cadherin was seen that correlated with altered cell morphology indicative of decreased intercellular adhesion. While ischemia was associated with activation of glycogen synthase kinase 3 beta (GSK-3beta), this did not correlate with increased phosphorylation of beta-catenin as assessed by Western blots using phosphoryl-specific antibodies. beta-Catenin was not localized to the nucleus by immunofluorescence in ischemic NRK cells, but rather a strong perinuclear signal was seen in reperfused cells. This was consistent with the finding that neither ischemia nor reperfusion activated the transcriptional activity of beta-catenin as assessed by the TCF-optimal promoter (TOPFlash) construct. However, NRK cells possess a competent Wnt pathway, as challenge with lithium chloride elicited a ten-fold increase in luciferase activity. These results suggest that ischemia-induced disruption of cadherin/catenin complexes is not sufficient to stimulate beta-catenin transcriptional activity in NRK cells.

Is non-steroidal anti-inflammaory drug (NSAID) enteropathy clinically more important than NSAID gastropathy?

The side effects of conventional non-steroidal anti-inflammatory drugs (NSAIDs) on the stomach is undoubtedly a serious public health problem contributing significantly to the morbidity and mortality of patients receiving these drugs. However, the damage of NSAIDs is not confined to the stomach. Indeed the short term and long term damage of NSAIDs on the small bowel (NSAID enteropathy) is more frequent than NSAID gastropathy. Furthermore, NSAID enteropathy is associated with complications (bleeding and protein loss). While many of these are mild, the serious events (significant bleeding, perforation, obstruction, and sudden death) are frequent as that reported for NSAID gastropathy. The diagnosis of NSAID enteropathy has been greatly aided by the introduction of wireless capsule enteroscopy.

Gender, Internet use, and sexual behavior orientation among young Nigerians.

This study examined the influence of gender and Internet use on the sexual behavior orientation of young adults in Nigeria. Using an ex-post-facto design, data were collected from a total of 231 participants. Results of the hierarchical regression model provided support for the influence of gender and Internet use on sexual behavior orientation among young Nigerians. Further, results also revealed an interaction effect; as the use of the Internet increased, male participants reported a greater extent of risky sexual behavior orientation than their female counterparts. The findings were explained in the context of the theoretical foundations of the study, while practical implications for combating youths' risky sexual behavior orientation were highlighted.

Reproductive, sexual and contraceptive behaviour of adolescents in Niger State, Nigeria.

This is a multi-stage random sampling study involving 896 male and female adolescents aged 11-25 years in Niger State of Nigeria. Thirty three per cent of them had already had first sexual experience. Only 3.6% were married. Most of the Gwari and Hausa respondents acknowledged that they married at an earlier age than the Yoruba respondents. One half of those who were sexually experienced had more than one sexual partner. Majority of the respondents were informed about HIV/AIDS and STDs. More Gwari and Hausa respondents felt that HIV infection could be prevented by not having multiple sexual partners than Yoruba and Igbo respondents. A wide disparity between contraceptive knowledge and use was found. Knowledge rate was between 41.9% and 63.8%, while use rate was between 0.7% and 12.5% for the contraceptive methods studied. Condom knowledge and use rate was highest. For prevention of HIV/AIDS, more males than females thought condom was useful. Most Gwari and Hausa respondents did not use any FP method during their first sexual relationships. It is imperative for reproductive health programmes to intensify efforts in improving adolescents' attitude towards sexual risk and motivate them to exhibit behaviours that limit it.

Overexpression of MMP-7 Increases Collagen 1A2 in the Aging Kidney.

The percentage of the U.S. population over 65 is rapidly increasing, as is the incidence of chronic kidney disease (CKD). The kidney is susceptible to age-dependent alterations in structure, specifically tubulointerstitial fibrosis, that lead to CKD. Matrix metalloproteinases (MMPs) were initially characterized as extracellular matrix (ECM) proteinases; however it is clear that their biological role is much larger. We have observed increased gene expression of several MMPs in the aging kidney, including MMP-7. MMP-7 overexpression was observed starting at 16 months, and over a 500 fold up-regulation in 2 year-old animals. Overexpression of MMP-7 is not observed in age-matched, calorically restricted controls that do not develop fibrosis and renal dysfunction, suggesting a role in the pathogenesis. In order to delineate the contributions of MMP-7 to renal dysfunction, we overexpressed MMP-7 in NRK-52E cells. High-throughput sequencing of the cells revealed that two collagen genes, Col1a2 and Col3a1, were elevated in the MMP-7 overexpressing cells. These two collagen genes were also elevated in aging rat kidneys and temporally correlated with increased MMP-7 expression. Addition of exogenous MMP-7, or conditioned media from MMP-7 overexpressing cells also increased Col1A2 expression. Inhibition of PKA, src, and MAPK signaling at p38 and ERK was able to attenuate the MMP-7 up-regulation of Col1a2. Consistent with this finding, increased phosphorylation of PKA, src and ERK was seen in MMP-7 overexpressing cells and upon exogenous MMP-7 treatment of NRK-52E cells. These data suggest a novel mechanism by which MMP-7 contributes to the development of fibrosis leading to CKD.

Workplace fairness and emotional exhaustion in Nigeria police: the moderating role of gender.

This study examined the moderating role of gender in the relationship between perceived workplace fairness and reported level of emotional exhaustion among a sample of Nigeria police. A total of 214 participants took part in the cross-sectional survey. Results of the moderated hierarchical regression analysis provided support for gender as a moderating variable in the relationship between perceived workplace fairness and emotional exhaustion, such that perceived workplace fairness was a stronger predictor of emotional exhaustion among male police than for female police. The practical implications for the management of emotional exhaustion in general, and for the Nigeria police in particular, were emphasized.

Promoter methylation is associated with the age-dependent loss of N-cadherin in the rat kidney.

The cadherins are cell adhesion molecules required for cellular homeostasis, and N-cadherin is the predominant cadherin expressed in proximal tubular epithelial cells in humans and rats. Our laboratory previously reported an age-dependent decrease in renal N-cadherin expression; the levels of N-cadherin mRNA and protein expression decreased in parallel, implicating a transcriptional mechanism in the age-dependent loss of expression (19). In this study, we examined the hypothesis that promoter hypermethylation underlies the loss of N-cadherin expression in aging rat kidney. We cloned the 5' flanking region of the rat N-cadherin gene and observed basic promoter activity in a 3,992-bp region localized immediately upstream of the ATG start site. Nucleotide analysis revealed 87% identity with the human N-cadherin minimal promoter region. Consistent with a role for regulation by DNA methylation, we found that a dense CpG island, which spans 1,104 bp (-1,158 to -55), flanks the rat N-cadherin gene; a similar CpG profile was found in the human N-cadherin 5' flanking region. Methylation-specific PCR analysis demonstrated that the promoter region of N-cadherin is heavily methylated in aged, but not young, rat kidney. Interestingly, the promoter is not methylated in age-matched, calorically restricted animals. In contrast, the promoter region is not methylated in either young or aged rat liver; this corresponds to the finding that aging is not associated with decreased N-cadherin expression in the liver. In addition, N-cadherin expression is markedly induced in NRK-52E cells treated with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, further suggesting that methylation at CpG in the promoter region may underlie the age-dependent decrease in renal N-cadherin expression.