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.     

Living donor liver transplantation.

Initially living donor liver transplantation (LDLT) was almost exclusively performed in infants and children. Adult LDLT programmes were initiated several years later. In the west this programme was introduced in view of a critical shortage of deceased donors and a constant increase in waiting list mortality. At present, this procedure is accepted as a therapeutic option for patients with end-stage liver disease to make up for the shortage of donor organs from dead patients. In Asia, however, LDLT has become the predominant means of liver transplantation as donor organs from the diseased cannot be used for religious and ethical reasons. Although there have been significant improvements in surgical techniques and consequently in recipient outcome over recent years, the LDLT procedure is still associated with donor morbidity and even mortality. The overall reported donor mortality was 0.2% and donor morbidity ranged between 0% and 100%. Biliary complications and infections were the most commonly reported donor complications. Therefore, a thorough medical as well as psychological evaluation of the donor and recipient are necessary prior to this procedure. To date, LDLT comprises less than 5% of adult liver transplantations in Europe and in the United States. Recipient and graft survival are almost identical to those seen with liver transplantations from deceased donors (DD). Biliary and vascular complications are more often seen in the LDLT setting. So far, no studies have focussed on the impact of LDLT on waiting list mortality. There is international consensus that this procedure should be restricted to centres with large experience in deceased donor liver transplantations as well as in hepatobiliary surgery. Ethical issues, optimal utility and application of adult LDLT and optimal recipient and donor characteristics have yet to be defined.     

Staging-laparoscopy

Summary. The so-called extended diagnostic laparoscopy (EDL) facilitates the comprehensive exploration of the abdominal cavity, thus improving the precision of the pretherapeutic tumor staging in gastrointestinal malignancies. EDL comprises visual inspection with a specific preparation of all relevant sites, laparoscopic sonography and retrieval of samples for biopsy and cytology. Additional relevant therapeutic information was obtained through EDL in 40.5 % of gastric cancer patients. EDL could be of similar importance for diagnosing esophageal, hepatobiliary and pancreatic malignancies.      

Laparoscopic gastrojejunostomy and endoscopic biliary stent placement for palliation of incurable gastric outlet obstruction with cholestasis

Background: For patients with incurable malignant gastric outlet obstruction and cholestasis, laparoscopic gastrojejunostomy combined with endoscopic biliary stent placement seems to offer a minimally invasive palliation. Methods: We retrospectively analyzed the data of 16 patients submitted to laparoscopic gastrojejunostomy. Laparoscopic gastroenterostomy was performed as an antecolic, side-to-side gastrojejunostomy with enteroenterostomy. In 12 patients cholestasis was relieved preoperatively by stent placement via endoscopy (n= 6, 37.5%), percutaneous access (n= 5, 31%) or bilioenteric anastomosis (n= 1, 6.25%). One patient needed a percutaneous Yamakawa prosthesis postoperatively. Results: Mean operative time was 126 min. There were no intraoperative complications. In one patient conversion to open surgery became necessary because of extensive adhesions. The only postoperative complication was bleeding from a trocar site requiring reintervention; there was no mortality. Median postoperative hospital stay was 7 days. Delayed gastric emptying was observed in 3 (18.7%) patients. Median survival was 87 days after the operation. All patients died from their primary disease but could maintain oral intake during the remaining survival time. Conclusions: We conclude that laparoscopic gastrojejunostomy and endoscopic or percutaneous biliary stenting provide a good functional result while impairing the quality of life only to a minimal extent. Received: 7 May 1996/Accepted: 12 December 1996     

Intestino-esophageal reflux following gastrectomy. Mechanism of action and effectiveness of esophago-jejunoplication

The influence of the type of reconstruction after gastrectomy upon the postoperative reflux was analyzed in 30 patients. The refluxed material could be directly gained by the long-term reflux aspiration test and, thus, the quality including bile acids could be evaluated. After esophago-jejunoplication and Roux en Y-derivation 5 out of 7 patients were asymptomatic; only one patient suffered from mild esophagitis. Total bile acid concentration was near to the test systems sensitivity. The result in 11 patients after esophago-jejunostomy without Y-en Roux, but with a preserved lower esophageal sphincter (LES) are similar to the former group, whereas in all cases of 12 patients in whom the LES was resected, severe reflux esophagitis and excessively elevated bile acid concentrations were present. These results confirm that a jejunoplication supports the antireflux effect of preserved parts of the LES. If--for oncologic reasons--the LES has to be resected, free intestinal-esophageal reflux is following. In these cases a Roux en Y-derivation is required.     

Multimodal, Multidimensional Models of Mouse Brain

Summary:  Naturally occurring mutants and genetically manipulated strains of mice are widely used to model a variety of human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison and to facilitate the integration of anatomic, genetic, and physiologic observations from multiple subjects and experiments. We have developed digital atlases of the C57BL/6J mouse brain (adult and neonate) as comprehensive frameworks for storing and accessing the myriad types of information about the mouse brain. Along with raw and annotated images, these contain database management systems and a set of tools for comparing information from different techniques and different animals. Each atlas establishes a canonical representation of the mouse brain and provides the tools for the manipulation and analysis of new data. We describe both these atlases and discuss how they may be put to use in organizing and analyzing data from mouse models of epilepsy.     

Surgery for right ventricle to pulmonary artery conduit obstruction: risk factors for further reoperation.

OBJECTIVE: To identify the surgical approaches and risk factors which influence longevity of right ventricle to pulmonary artery (RV-PA) conduits following first reoperation for obstruction. METHODS: Between January 1993 and August 2003, 114 patients underwent 141 reoperations for RV-PA conduit obstruction. Diagnoses included 'Truncus Arteriosus' (n=52), 'Pulmonary atresia/Tetralogy of fallot' (n=39), 'Double outlet right ventricle' (n=10), 'Transposition of great arteries, VSD, and pulmonary atresia' (n=9), and the 'Ross operation' (n=4). All patients had undergone a previous biventricular repair. The first reoperation for conduit obstruction was performed in 112 hospital survivors by: total conduit replacement (Group A, n=73) with valved (homograft=10 and xenograft=54) or non-valved (n=9) conduit, and patch enlargement of the obstructed RV outflow tract with preservation of the posterior and sides of the conduit wall after removing of the fibrocalcific peel and degenerated valve (Group B, n=39). Mean age at first reoperation was 8.8+/-6.7 and 7.5+/-5.3 years in patients of groups A and B, respectively. Seven patients in Group A and 18 in Group B required a second reoperation and two patients in Group B a third reoperation. RESULTS: There were two hospital deaths and no late deaths. Mean follow-up was 5.8+/-3.2 years. Risk factors for second reoperation by univariate analysis were: homograft conduit use (P=0.004), Group B surgical approach (P=0.0001), higher RV-PA systolic pressure gradient at discharge (P=0.02), and age <5-years-old (P=0.01). Multivariate analysis showed that inclusion in Group B and younger age (<5-years-old) at repair were independent risk factors for second reoperation. Group B surgical approaches had higher RV-PA systolic pressure gradient at discharge (P=0.02) and required more PA bifurcation repair at the time of second reoperation (P=0.05). Freedom from second reoperation for conduit obstruction was significantly higher in Group A patients at 5 and 8 years (P<0.04) and those with xenografts rather than homograft (P=0.04). CONCLUSIONS: Our results support the optimal surgical approach for RV-PA conduit obstruction is total replacement with a xenograft. RV outflow reconstruction by other techniques without complete dissection of PA bifurcation does not completely relieve the stenosis and could cause early restenosis. Higher systolic gradients at discharge and younger age at first reoperation are predictors of earlier reoperation.