Expression and prognostic significance of 14-3-3sigma and ERM family protein expression in periampullary neoplasms

Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5' region of 14-3-3sigma (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers. We investigated the prognostic significance of aberrant expression of 14-3-3sigma and the ERM proteins (Ezrin, radixin, Moesin) in a series of invasive periampullary adenocarcinomas including 300 infiltrating pancreatic adenocarcinomas, 54 ampullary adenocarcinomas, and 33 noninvasive intraductal papillary mucinous neoplasms from patients who underwent pancreaticoduodenal resection at The Johns Hopkins Hospital, Baltimore, MD, between 1991 and 2003. Two-hundred fourty-four (82%) primary infiltrating adenocarcinomas of the pancreas demonstrated positive expression of the 14-3-3sigma, 45 (15%) showed weak immunolabelling, and 9 (3%) were negative. 201 (68%) showed positive immunolabeling of the ERM proteins, 75 (25%) demonstrated weak expression and 20 (7%) no expression. A similar proportion of ampullary cancers showed 14-3-3sigma and ERM protein expression. Expression of 14-3-3sigma and ERM protein was more likely in poorly differentiated cancers (p = 0.00005), and their expression was associated with poor survival in univariate analysis (p = 0.09). By multivariate analysis, patients whose cancers expressed 14-3-3sigma, but not ERM tended to have a poorer prognosis (Hazard ratio, 1.4; 0.9-2.2, p = 0.14). Aberrant expression of 14-3-3sigma may contribute to the outcome of patients with pancreatic ductal adenocarcinoma.     

Bowel injury in gynecologic laparoscopy

STUDY OBJECTIVE: To review surveys of the last decade on bowel injuries to evaluate the prevalence, causes, management, and outcomes of these events occurring during or as a result of laparoscopy. DESIGN: Retrospective evaluation (Canadian Task Force classification II-2). SETTING: Surveys and databases. PATIENTS: None. INTERVENTION: Data analysis. MEASUREMENTS AND MAIN RESULTS: Combined data show that diagnostic and minor operative laparoscopy are associated with a 0.08% risk of bowel injury, and in major operative laparoscopy the risk increases to 0.33%. Injuries occurring during access and operative procedure decrease significantly with experience, but even in experienced hands injury during access cannot be avoided. Delayed diagnosis remains a major problem. Up to 15% of these injuries are not diagnosed during laparoscopy, and one of five cases of delayed diagnosis results in death. Perioperative diagnosis and immediate repair by laparoscopy or laparotomy reduce the likelihood of severe complications and consequently medicolegal actions. CONCLUSIONS: Several surveys on complications of gynecologic laparoscopy tend to underestimate the risk of bowel injury. Prevention starts by awareness that such injury is an inherent risk of the technique, even in hands of experienced surgeons.     

Post-mortem findings and causes of death of harbour porpoises (Phocoena phocoena) stranded from 1990 to 2000 along the coastlines of Belgium and Northern France

Between the years 1990 and 2000, an attempt was made to determine the causes of death of 55 harbour porpoises stranded along the Belgian and northern French coasts. From 1990 to 1996, only five carcasses were collected as against seven in 1997, eight in 1998, 27 in 1999 and eight in 2000. The sex ratio was normal and most of the animals were juvenile. The most common findings were emaciation, severe parasitosis and pneumonia. A few cases of fishing net entanglement were observed. The main microscopical lesions were acute pneumonia, massive lung oedema, enteritis, hepatitis and gastritis. Encephalitis was observed in six cases. No evidence of morbillivirus infection was detected. Pneumonia was associated with bacteria or parasites, or both. The causes of death and the lesions were similar to those previously reported in other countries bordering the North Sea. The cause of the increased numbers of carcasses in 1999 was unclear but did not include viral epizootics or net entanglement. A temporary increase in the porpoise population in the southern North Sea may have been responsible.     

Investigation of the infertile couple: a one-stop outpatient endoscopy-based approach

Transvaginal hydrolaparoscopy (THL) is a new culdoscopic technique for exploration of the pelvic cavity that takes advantage of micro-endoscopic technology and uses aquaflotation for inspection of the tubo-ovarian structures. In infertility patients, THL is systematically combined with mini-hysteroscopy, chromopertubation, fimbrioscopy and, when indicated, salpingoscopy. Mini-hysteroscopy in combination with the chromopertubation test allows accurate assessment of the uterine cavity and tubal patency. The transvaginal access combined with the aquaflotation during THL facilitates detailed inspection of the tubo-ovarian structures and detection of subtle pelvic disease. This combined transvaginal endoscopic approach allows complete evaluation of the reproductive tract. THL is better tolerated than hysterosalpingography, less invasive than standard laparoscopy, and can be used safely as a first line investigation of the female partner in a one-stop infertility clinic.     

Promoting awareness of neonatal menstruation

Neonatal uterine bleeding (NUB) has been carefully studied in the past through case reports, small series, clinical cohort studies, pathology investigations of fetal and neonatal. Following a historical recount, this review summarizes biological mechanisms conditioning NUB, starting from the persistence till birth of an 'ontogenetic progesterone resistance' (OPR), causing decreased responsiveness of target tissues to bioavailable progesterone. Several pregnancy-related conditions, such as preeclampsia, fetal growth restriction, prematurity, post-maturity and even Rhesus or ABO incompatibility, influence the occurrence of NUB. It seems therefore that the phenomenon is precipitated by chronic fetal distress. When present, OPR may persists until telarche; as a consequence, if pregnancy occurs in early teenage, the disorder known as “defective deep placentation” may ensue, increasing the risk of obstetrical syndromes. In the presence of NUB, retrograde shedding into the peritoneal cavity of endometrial stem/progenitor and niche cells may occur. There, given the right environment, these cells can survive and become activated at the time of telarche, causing the specific phenotype of early-onset endometriosis. In conclusion, neonatal menstruation is a fetal distress indicator and can alter the incidence of a variety of pathological conditions later in life. For this reason, it should be carefully recorded and the parents informed.     

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 1. Effects on metabolism

Introduction: The risk-benefit profile of any pharmacologic agent must be evaluated against risks connected with the events to be avoided. This is especially true in the case of hormonal contraception, not intended to combat a disease.

Over the six decades during which their use has progressively expanded, the risk-benefit profile of combined oral contraceptives (COC) has substantially changed, with new combinations, dosages and mode of administration appearing on the market.

Area covered: In a series of articles, recent information on the complex issue of COC risks and benefits will be reviewed in the hope of providing an updated picture.

The present article reviews metabolic changes occurring during use of modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), often compared to classic compounds, such as levonorgestrel.

Three categories of metabolic effects in healthy women are detailed: on carbohydrates, lipid and bone mineral content.

Expert commentary: Overall, the picture is reassuring: the new generations of progestins are basically devoid of androgenic, estrogenic or glucocorticoid related side-effects. This should result in an improved safety profile, although past history teaches us that that large comparative and surveillance studies are required before firm conclusions can be drawn.

At any rate, available evidence indicates that metabolic effects of third and fourth generation progestins, especially when they are combined with natural estrogens, are minimal and, if used in healthy women, should not cause concern.     

Pharmacodynamics of combined estrogen–progestin oral contraceptives: 4. Effects on uterine and cervical epithelia

ABSTRACT

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.

Areas covered: The Endometrial effects of progestins and estrogens; combined monophasic high- (50 μg), medium- (30 μg), low- (20 μg), ultralow- (15 μg) estrogen content; sequential regimens; multiphasic combinations; treatment schedules.

Cervical effects of combined high-dose and sequential combinations, including evidence for an increase in malignant lesions.

Expert opinion: Overall, combined oral contraceptives (COCs) inhibit normal proliferative changes and the endometrium becomes thin, narrow, with widely spaced glands and pre-decidual changes in the stroma. During the first few cycles the progestin induces a coexistence of proliferative and secretory features; with time, the picture changes because the progestin induces a down-regulation of estrogen receptors, resulting in tortuous glands similar to those in the secretory phase, but characterized by a quiescent, atrophic glandular epithelium.

In the cervical epithelium, under the influence of high-dose COCs, endocervical glands became hypersecretory and in some instances, distinctive type of atypical polypoid endocervical hyperplasia is found.