A deep learning system for detection of early Barrett's neoplasia: a model development and validation study.

BACKGROUND: Computer-aided detection (CADe) systems could assist endoscopists in detecting early neoplasia in Barrett's oesophagus, which could be difficult to detect in endoscopic images. The aim of this study was to develop, test, and benchmark a CADe system for early neoplasia in Barrett's oesophagus. METHODS: The CADe system was first pretrained with ImageNet followed by domain-specific pretraining with GastroNet. We trained the CADe system on a dataset of 14 046 images (2506 patients) of confirmed Barrett's oesophagus neoplasia and non-dysplastic Barrett's oesophagus from 15 centres. Neoplasia was delineated by 14 Barrett's oesophagus experts for all datasets. We tested the performance of the CADe system on two independent test sets. The all-comers test set comprised 327 (73 patients) non-dysplastic Barrett's oesophagus images, 82 (46 patients) neoplastic images, 180 (66 of the same patients) non-dysplastic Barrett's oesophagus videos, and 71 (45 of the same patients) neoplastic videos. The benchmarking test set comprised 100 (50 patients) neoplastic images, 300 (125 patients) non-dysplastic images, 47 (47 of the same patients) neoplastic videos, and 141 (82 of the same patients) non-dysplastic videos, and was enriched with subtle neoplasia cases. The benchmarking test set was evaluated by 112 endoscopists from six countries (first without CADe and, after 6 weeks, with CADe) and by 28 external international Barrett's oesophagus experts. The primary outcome was the sensitivity of Barrett's neoplasia detection by general endoscopists without CADe assistance versus with CADe assistance on the benchmarking test set. We compared sensitivity using a mixed-effects logistic regression model with conditional odds ratios (ORs; likelihood profile 95% CIs). FINDINGS: Sensitivity for neoplasia detection among endoscopists increased from 74% to 88% with CADe assistance (OR 2·04; 95% CI 1·73-2·42; p<0·0001 for images and from 67% to 79% [2·35; 1·90-2·94; p<0·0001] for video) without compromising specificity (from 89% to 90% [1·07; 0·96-1·19; p=0·20] for images and from 96% to 94% [0·94; 0·79-1·11; ] for video; p=0·46). In the all-comers test set, CADe detected neoplastic lesions in 95% (88-98) of images and 97% (90-99) of videos. In the benchmarking test set, the CADe system was superior to endoscopists in detecting neoplasia (90% vs 74% [OR 3·75; 95% CI 1·93-8·05; p=0·0002] for images and 91% vs 67% [11·68; 3·85-47·53; p<0·0001] for video) and non-inferior to Barrett's oesophagus experts (90% vs 87% [OR 1·74; 95% CI 0·83-3·65] for images and 91% vs 86% [2·94; 0·99-11·40] for video). INTERPRETATION: CADe outperformed endoscopists in detecting Barrett's oesophagus neoplasia and, when used as an assistive tool, it improved their detection rate. CADe detected virtually all neoplasia in a test set of consecutive cases. FUNDING: Olympus.

Development and internal validation of an algorithm to predict intraoperative risk of inadvertent hypothermia based on preoperative data.

Intraoperative hypothermia increases perioperative morbidity and identifying patients at risk preoperatively is challenging. The aim of this study was to develop and internally validate prediction models for intraoperative hypothermia occurring despite active warming and to implement the algorithm in an online risk estimation tool. The final dataset included 36,371 surgery cases between September 2013 and May 2019 at the Vienna General Hospital. The primary outcome was minimum temperature measured during surgery. Preoperative data, initial vital signs measured before induction of anesthesia, and known comorbidities recorded in the preanesthetic clinic (PAC) were available, and the final predictors were selected by forward selection and backward elimination. Three models with different levels of information were developed and their predictive performance for minimum temperature below 36 °C and 35.5 °C was assessed using discrimination and calibration. Moderate hypothermia (below 35.5 °C) was observed in 18.2% of cases. The algorithm to predict inadvertent intraoperative hypothermia performed well with concordance statistics of 0.71 (36 °C) and 0.70 (35.5 °C) for the model including data from the preanesthetic clinic. All models were well-calibrated for 36 °C and 35.5 °C. Finally, a web-based implementation of the algorithm was programmed to facilitate the calculation of the probabilistic prediction of a patient's core temperature to fall below 35.5 °C during surgery. The results indicate that inadvertent intraoperative hypothermia still occurs frequently despite active warming. Additional thermoregulatory measures may be needed to increase the rate of perioperative normothermia. The developed prediction models can support clinical decision-makers in identifying the patients at risk for intraoperative hypothermia and help optimize allocation of additional thermoregulatory interventions.

Barrett's esophagus and esophageal adenocarcinoma are common after treatment for achalasia.

BACKGROUND: Achalasia is characterized by esophageal aperistalsis and impaired relaxation of the lower esophageal sphincter (LES). This contrasts with an insufficient LES, predisposing to gastro-esophageal reflux and Barrett's esophagus. The co-incidence of achalasia and BE is rare. Pneumatic dilatation (PD) may lead to gastro-esophageal reflux, Barrett's esophagus development, and esophageal adenocarcinoma. AIMS: To determine the incidence of Barrett's esophagus and esophageal adenocarcinoma in achalasia patients treated with PD. METHODS: We performed a single-center cohort follow-up study of 331 achalasia patients treated with PD. Mean follow-up was 8.9 years, consisting of regular esophageal manometry, timed barium esophagram, and endoscopy. RESULTS: Twenty-eight (8.4%) patients were diagnosed with Barrett's esophagus, one at baseline endoscopy. This corresponds with an annual incidence of Barrett's esophagus of 1.00% (95% CI 0.62-1.37). Hiatal herniation was present in 74 patients and 21 developed Barrett's esophagus compared to seven of 257 patients without a hiatal hernia. Statistical analysis revealed a hazard ratio of 8.04 to develop Barrett's esophagus if a hiatal hernia was present. Post-treatment LES pressures were lower in patients with Barrett's esophagus than in those without (13.9 vs. 17.4 mmHg; p = 0.03). Two (0.6%) patients developed esophageal adenocarcinoma during follow-up. CONCLUSIONS: Barrett's esophagus is incidentally diagnosed in untreated achalasia patients despite high LES pressures, but is more common after successful treatment, especially in the presence of hiatal herniation. Patients treated for achalasia should be considered for GERD treatment and surveillance of development of Barrett's esophagus, in particular, when they have low LES pressures and a hiatal herniation.

Electrosurgical bipolar vessel sealing versus conventional clamping and suturing for vaginal hysterectomy: a randomised controlled trial.

OBJECTIVE: To compare the effects of electrical bipolar vessel sealing and conventional suturing on postoperative pain, recovery, costs and micturition symptoms in women undergoing vaginal hysterectomy. DESIGN: Randomised controlled trial. SETTING: Eight teaching hospitals in the Netherlands. POPULATION: One hundred women scheduled to undergo vaginal hysterectomy for benign conditions excluding pelvic organ prolapse. METHODS: Women were randomised to vessel sealing or conventional surgery. The quality of life related to pelvic floor function was assessed using validated questionnaires before surgery and 6 months after surgery. Pain scores and recovery were assessed using a diary, including daily visual analogue scale scores, starting from the day before surgery until 6 weeks after surgery. MAIN OUTCOME MEASURES: Visual analogue scale pain scores, surgery time, blood loss, complications, quality of life related to pelvic floor function and costs. RESULTS: The evening after surgery, women in the vessel-sealing group reported significantly less pain (5.7 versus 4.5 on a scale of 0-10, P = 0.03), but after that pain scores were similar. Operation duration was shorter for vessel sealing (60 versus 71 minutes, P = 0.05). Blood loss and hospital stay did not differ. We observed no major difference in costs between the two interventions (2903 versus 3102 €, P = 0.26). Changes in micturition and defecation symptoms were not affected by the surgical technique used. CONCLUSION: Using vessel sealing during vaginal hysterectomy resulted in less pain on the first postoperative day, shorter operating time, similar morbidity and similar pelvic floor function. No major differences in costs were found between the two interventions.

Long-term esophageal cancer risk in patients with primary achalasia: a prospective study.

OBJECTIVES: Achalasia patients are considered at increased risk for esophageal cancer, but the reported relative risks vary. Identification of this risk is relevant for patient management. We performed a prospective evaluation of the esophageal cancer risk in a large cohort of achalasia patients with long-term follow-up. METHODS: Between 1975 and 2006, all patients diagnosed with primary achalasia in our hospital were treated and followed by the same protocol. After graded pneumatic dilatation, all patients were offered a fixed surveillance protocol including gastrointestinal endoscopy with esophageal biopsy sampling. RESULTS: We surveyed a cohort of 448 achalasia patients (218 men, mean age 51 years at diagnosis, range 4-92 years) for a mean follow-up of 9.6 years (range 0.1-32). Overall, 15 (3.3%) patients (10 men) developed esophageal cancer (annual incidence 0.34 (95% confidence interval 0.20-0.56)). The mean age at cancer diagnosis was 71 years (range 36-90) after a mean of 11 years (range 2-23) following initial presentation, and a mean of 24 years (range 10-43) after symptom onset. The relative hazard rate of esophageal cancer was 28 (confidence interval 17-46) compared with an age- and sex-identical population in the same timeframe. Five patients received a potential curative treatment. CONCLUSIONS: Although the gastro-esophageal cancer risk in patients with longstanding achalasia is much higher than in the general population, the absolute risk is rather low. Despite structured endoscopical surveillance, most neoplastic lesions remain undetected until an advanced stage. Efforts should be made to identify high-risk groups and develop adequate surveillance strategies.

Hindfoot endoscopy for posterior ankle impingement. Surgical technique.

BACKGROUND: The surgical treatment of posterior ankle impingement is associated with a high rate of complications and a substantial time to recover. An endoscopic approach to the posterior ankle (hindfoot endoscopy) may lack these disadvantages. We hypothesized that hindfoot endoscopy causes less morbidity and facilitates a quick recovery compared with open surgery. METHODS: Fifty-five consecutive patients with posterior ankle impingement were treated with an endoscopic removal of bone fragments and/or scar tissue. The symptoms were caused by trauma (65%) or overuse (35%). All patients were enrolled in a prospective protocol. At baseline, the age, sex, work and sports activities, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and preinjury Tegner scores were determined for all patients. At the time of follow-up, AOFAS hindfoot scores and Tegner scores were assessed and the time to return to work and sports activities was determined. Complications were recorded. Patients scored the overall result as poor, fair, good, or excellent by means of a 4-point Likert scale. RESULTS: The median duration of follow-up was thirty-six months, and no patient was lost to follow-up. The median AOFAS hindfoot score increased from 75 points preoperatively to 90 points at the time of final follow-up. The median time to return to work and sports activities was two and eight weeks, respectively. At the time of follow-up, patients in the overuse group were more satisfied than those in the posttraumatic group, and the AOFAS hindfoot scores were higher in patients in the overuse group (median, 100 points) compared with patients in the posttraumatic group (median, 90 points). A complication occurred in one patient who had a temporary loss of sensation of the posteromedial aspect of the heel. CONCLUSIONS: The outcome after endoscopic treatment of posterior ankle impingement compares favorably with the results of open surgery reported in the literature. Hindfoot endoscopy appears to cause less morbidity than open ankle surgery and facilitates a quick recovery. Patients treated for posterior ankle impingement caused by overuse have better results than those treated following trauma.

Hindfoot endoscopy for posterior ankle impingement.

BACKGROUND: The surgical treatment of posterior ankle impingement is associated with a high rate of complications and a substantial time to recover. An endoscopic approach to the posterior ankle (hindfoot endoscopy) may lack these disadvantages. We hypothesized that hindfoot endoscopy causes less morbidity and facilitates a quick recovery compared with open surgery. METHODS: Fifty-five consecutive patients with posterior ankle impingement were treated with an endoscopic removal of bone fragments and/or scar tissue. The symptoms were caused by trauma (65%) or overuse (35%). All patients were enrolled in a prospective protocol. At baseline, the age, sex, work and sports activities, American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores, and preinjury Tegner scores were determined for all patients. At the time of follow-up, AOFAS hindfoot scores and Tegner scores were assessed and the time to return to work and sports activities was determined. Complications were recorded. Patients scored the overall result as poor, fair, good, or excellent by means of a 4-point Likert scale. RESULTS: The median duration of follow-up was thirty-six months, and no patient was lost to follow-up. The median AOFAS hindfoot score increased from 75 points preoperatively to 90 points at the time of final follow-up. The median time to return to work and sports activities was two and eight weeks, respectively. At the time of follow-up, patients in the overuse group were more satisfied than those in the posttraumatic group, and the AOFAS hindfoot scores were higher in patients in the overuse group (median, 100 points) compared with patients in the posttraumatic group (median, 90 points). A complication occurred in one patient who had a temporary loss of sensation of the posteromedial aspect of the heel. CONCLUSIONS: The outcome after endoscopic treatment of posterior ankle impingement compares favorably with the results of open surgery reported in the literature. Hindfoot endoscopy appears to cause less morbidity than open ankle surgery and facilitates a quick recovery. Patients treated for posterior ankle impingement caused by overuse have better results than those treated following trauma.

[Abdominal pain and transit disorders following a laparoscopic procedure: be alert to a trocar hernia]. / Buikpijn en passagestoornissen na een laparoscopische ingreep: denk aan een trocart-hernia.

Three patients, three women aged 40, 64 and 75, suffered from a trocar hernia, a specific complication of laparoscopic surgery. This type of hernia may result in small bowel obstruction and normally appears within two weeks after laparoscopy. The usual presentation is that of abdominal pain with nausea and vomiting. Trocar herniation implicates the necessity of reposition and might result in bowel resection with prolonged hospital stay. The advice for prevention is to use a trocar with a diameter as small as possible, as the chance of a hernia occurring increases withthe use of larger trocars. Fascial closure is advised for trocars to mm and larger. With a growing number of procedures being performed laparoscopically, the importance of recognizing and preventing this complication is evident. Three cases illustrate the importance of early recognition of small bowel obstruction resulting from trocar herniation.

Oesophagitis is common in patients with achalasia after pneumatic dilatation.

BACKGROUND: Achalasia, an oesophageal motor disease, is associated with functional oesophageal obstruction. Food stasis can predispose for oesophagitis. Treatment aims at lowering of the lower oesophageal sphincter pressure, enhancing the risk of gastro-oesophageal reflux. Nevertheless, the incidence of oesophagitis after achalasia treatment is unknown. AIM: To investigate the incidence and severity of oesophagitis in achalasia patients treated with pneumatic dilatation. METHODS: A cohort of 331 patients with achalasia were treated with pneumatic dilatation and followed. Oesophagitis and stasis were assessed by endoscopy and inflammation was graded by histology. RESULTS: 251 patients were followed for a mean values of 8.4 years (range: 1-26). The average number of endoscopies with biopsy sample sets per patient was 4 (range: 1-17). Three patients had no histological signs of oesophagitis throughout follow-up, 139 had oesophagitis grade 1, 49 oesophagitis grade 2 and 60 grade 3. Specialized intestinal metaplasia was found in 37 patients. The association between endoscopic food stasis and histological inflammation was significant. The association between endoscopic signs of oesophagitis and histological inflammation was poor. CONCLUSIONS: Forty percent of the achalasia patients develop chronic active or ulcerating oesophagitis after treatment. Inflammation was associated with food stasis. Because the sensitivity of endoscopy to detect inflammation is low, surveillance endoscopy with biopsy sampling and assessment of stasis is warranted to detect early neoplastic changes.

[Chronic diarrhoea: the importance of an accurate medical history]. / Chronische diarree; het belang van de anamnese.

Four patients, two women aged 29 and 42 years and two men aged 45 and 34 years, with longstanding complaints of (watery) diarrhoea were referred for a second opinion after extensive and costly analysis, including numerous examinations. An accurate medical history revealed deviant food patterns with abundant intake of coffee and sugar or sugar-containing products like cola or sweeteners in all four patients. Coffee (and caffeine) has a stimulating effect on both intestinal motility and net secretion, possibly leading to diarrhoea. Over-consumption of sugars and sweeteners (sometimes added to medication) can also cause osmotic diarrhoea. In all four patients, dietary advice was sufficient to resolve the diarrhoea, thus emphasizing once more the importance of an accurate and complete medical history.

A randomized comparison of post-operative pain, quality of life, and physical performance during the first 6 weeks after abdominal or vaginal surgical correction of descensus uteri.

AIMS: With respect to urogenital function, vaginal hysterectomy combined with anterior and/or posterior colporraphy has been shown to be superior to abdominal sacrocolpopexy with preservation of the uterus. We performed a randomized trial to compare the effects of both procedures on pain, quality of life and physical performance during the first six weeks after surgery. METHODS: Eighty-two patients were randomized to have surgery either by vaginal or abdominal approach. All patients were asked to complete the RAND-36 before surgery and 6 weeks after surgery and to keep a diary for the first 6 weeks after surgery. This diary assessed the pain perception and use of pain medication, bother of limitations due to the surgery and performance of daily activities after surgery. These outcomes were compared. RESULTS: All patients completed the RAND-36 and 68 patients completed the diary. Patients who had undergone abdominal surgery had a statistically lower score on the health change domain (56 vs 68), bodily pain domain (63 vs 80) and mental health domain (74 vs 81) of the RAND-36, as compared to patients who had undergone vaginal prolapse surgery. During hospital stay, the abdominal group experienced on average more days of pain (4.5 vs 3.0) and impaired mobility (3.7 vs 2.9) as compared to the vaginal group. Patients received more pain medication following abdominal surgery as compared to vaginal surgery. CONCLUSIONS: The vaginal operation to correct a descensus uteri is associated with less pain, better quality of life and better mobility during the first 6 weeks of the recovery period as compared to the abdominal approach.

Percutaneous endoscopic gastrostomy: complications and suggestions to avoid them.

OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) tubes have become an excellent alternative for the long-term management of patients with proximal obstructions of the gastrointestinal tract. However, their use has limitations and can be associated with serious complications. We therefore studied the frequency and severity of complications related to the use of PEG tubes in our clinic. DESIGN: All adults (aged 18 years and above) in whom a PEG tube was placed between January 1 1994 and January 1 1999 at the Free University Hospital in Amsterdam were included in this study. In initial cases, the indication and procedure were individually judged according to a liberal protocol. However, after several major complications, a strict procedure protocol was implemented in September 1996. RESULTS: During the study period, 263 PEG tubes were placed in 254 patients with head and neck cancer (n = 183; 70%), neurological disorders (n = 52; 20%) or severe upper gastrointestinal motility disorders (n = 28; 11%). In period I, 167 PEG tubes were placed and in period II, 96 PEG tubes were inserted. Patients were followed for a median 111 days. Minor complications occurred in 13% of the patients. Major complications occurred in 8% of the patients. In period I, the percentage of major complications was higher than in period II (9.5% versus 6%). CONCLUSION: PEG tube placement is a safe procedure when performed according to strict guidelines. By doing so, PEG tubes allow optimal feeding for prolonged periods with the occasional need for replacement of the tube. PEG tubes should not be introduced in acutely ill patients, patients with a short life expectancy and preferably not to patients with severe coughing.

Endoscopic calcaneoplasty.

Endoscopic calcaneoplasty offers access to the retrocalcaneal space, thereby making it possible to remove inflamed retrocalcaneal bursa as well as the posterosuperior part of the calcaneus in applicable cases of painful hindfoot. In this study, endoscopic calcaneoplasty was performed in 21 procedures in 20 patients. All of the patients had typical complaints of inflammation of the retrocalcaneal bursa that were unresponsive to nonoperative treatment for more than 6 months. In all patients a superior calcaneal angle of more than 75 degrees and positive parallel pitch lines were present on the lateral calcaneal radiograph. The mean follow-up was 3.9 years (range, 2 to 6.5). There were no surgical complications and no postoperative infections. One patient had a fair result, 4 patients had good results, and the remaining 15 patients had excellent results. Whether this operation is performed by endoscopic or open technique, enough bone must be removed to prevent impingement of the bursa between the calcaneus and Achilles tendon. Endoscopic calcaneoplasty is a minimally invasive technique performed in an outpatient setting and combined with a functional rehabilitation program. The procedure has low morbidity. Patients have a short recovery time and quickly resume work and sports.

A 2-portal endoscopic approach for diagnosis and treatment of posterior ankle pathology.

We describe a 2-portal endoscopic approach of the hindfoot with the patient in the prone position. By means of this approach, it is possible to visualize and treat a variety of posterior ankle problems. Not only can pathology of the posterior ankle joint and subtalar joint be visualized and treated, but also periarticular pathology, such as calcifications or scar tissue, can be diagnosed and treated. We describe a professional ballet dancer with chronic flexor hallucis longus tendinitis and a posterior ankle impingement syndrome caused by an os trigonum of both ankles. The patient was successfully treated by removing the os trigonum and releasing the flexor hallucis longus tendon. She resumed her professional activities within 2 months after endoscopic treatment.

Survival of malnourished head and neck cancer patients can be predicted by human leukocyte antigen-DR expression and interleukin-6/tumor necrosis factor-alpha response of the monocyte.

BACKGROUND: Patients with advanced stages of head and neck cancer are often characterized by malnutrition and by an impaired immune system. Because some of the suppressed immune parameters were shown to be of prognostic importance in trauma and sepsis, we investigated whether these would also correlate with survival in head and neck cancer. METHODS: Severely malnourished head and neck cancer patients undergoing ablative and reconstructive surgery were followed prospectively and their perioperative immune parameters were related to long-term survival. RESULTS: Forty-nine patients with a preoperative weight loss of more than 10% were followed up for a period of at least 16 months after surgery. Analyses of variance revealed that preoperative human leukocyte antigen-DR (HLA-DR) expression on monocytes and endotoxin-induced production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were different between patients who survived and patients who died. Proportional hazards identified a weight loss of more than 12%, the presence of coexistent disease, and an HLA-DR expression on monocytes below the cutoff points (mean fluorescence index < 15, peak channel index < 9) to be of significant influence on survival. CONCLUSIONS: In addition to known prognostic parameters such as tumor stage, coexistent disease, and weight loss, the immune parameters HLA-DR expression on monocytes and endotoxin-induced cytokine production may carry prognostic value in cancer patients. Immunomodulating therapies leading to improvement of these parameters might in the future lead to increased options for treatment.

Graduated elastic compression stockings on a stroke unit: a feasibility study.

BACKGROUND: thrombo-embolic complications are important causes of morbidity and mortality after acute stroke. Anticoagulant prophylaxis is contraindicated in intracerebral haemorrhage and not recommended in acute ischaemic stroke because of increased risk of cerebral haemorrhage. Graduated elastic compression stockings are a simple alternative but are not widely used in stroke patients, perhaps because of perceived contraindications and problems with tolerability. OBJECTIVES: to establish the feasibility and tolerability of graduated compression stockings on a stroke unit. DESIGN: we assessed 112 consecutive stroke patients for contraindications to and tolerability of graduated compression stockings. MEASUREMENTS: we used clinical indices and ankle-brachial Doppler pressure measures to assess suitability. We prospectively assessed tolerability of the stockings. RESULTS: Ninety-four (84%) of the 112 patients had no contraindications to the use of the stockings. The most common contraindication was an ankle-brachial index of <0.8. Other contraindications were marked dependent leg oedema (1/18) and severe venous ulceration. Eighty-nine (95%) of the 94 patients tolerated the stockings and wore them until discharge. Skin irritation was the most common reason for intolerance. CONCLUSIONS: contraindications to the use of graduated compression stockings can be defined using clinical criteria and a Doppler machine to calculate an ankle-brachial pressure index. If this is done, tolerability is excellent. This approach may be a useful alternative in preventing venous thrombo-embolism in stroke patients.

The effect of low-dose 3-keto-desogestrel added to a copper-releasing intrauterine contraceptive device on menstrual blood loss: a double-blind, dose-finding, placebo-controlled study.

OBJECTIVE: We sought to establish the lowest dose of 3-keto-desogestrel, when added to a copper-releasing intrauterine contraceptive device, that is needed to reduce menstrual blood loss to a very low level and to treat (essential) menorrhagia successfully. STUDY DESIGN: A double-blind group comparative study was designed in which 203 healthy women with or without menorrhagia were enrolled and randomized to four different Multiload Cu250 intrauterine contraceptive devices, releasing 0 (control), 1.5, 3, or 6 microg of 3-keto-desogestrel daily. Menstrual blood loss, hemoglobin, and serum ferritin levels were determined before and during treatment. RESULTS: All 3-keto-desogestrel-copper intrauterine contraceptive devices reduced menstrual blood loss significantly, causing a reduction of up to 30 to 40 mL after 12 months of use. All women with essential menorrhagia were considered to have been successfully treated after 6 months of use. Serum ferritin levels rose with all three 3-keto-desogestrel-loaded devices. CONCLUSION: A Multiload Cu250 intrauterine contraceptive device releasing 1.5 microg of 3-keto-desogestrel daily is able to reduce menstrual blood loss to a very low level and to replete body iron stores in women with or without menorrhagia. Higher doses have no superior effect.

Histological patterns in endometrial samples from perimenopausal women.

OBJECTIVE: Evaluation of endometrial histology patterns in perimenopausal women. METHODS: Endometrial biopsies (202) taken from perimenopausal women by suction curette were assessed by light microscopy. RESULTS: Out of 142 adequate specimens a total of 82 (57.7%) specimens could not be classified in the well-defined categories of the fertile period because of mixed histological patterns. Of the 142 specimens, 59 (41.5%) showed abnormal secretory endometrium, three (2%) disordered proliferative endometrium and 20 (14.1%) a mixture of non-secretory and secretory endometrium. CONCLUSION: The often used histological classification for endometrium, with well-defined regular patterns based on normal cyclic changes, often does not apply to endometrial tissue obtained from perimenopausal women due to a mixed pattern within one biopsy.

Bleeding patterns and endometrial histology during administration of low-dose estradiol sequentially combined with dydrogesterone.

OBJECTIVE: To determine bleeding patterns and endometrial response in postmenopausal women taking low-dose (1 mg) estradiol in a sequential combined formulation with 5 or 10 mg dydrogesterone. METHODS: A total of 151 postmenopausal women were allocated randomly to 5 or 10 mg dydrogesterone during cycle days 15-28 in a sequential oral formulation with 1 mg estradiol continuously during 13 cycles of 28 days. Occurrence of vaginal bleeding was recorded daily and analyzed in accordance with World Health Organization (WHO) standards. Endometrial biopsies, obtained at baseline and cycle days 25-27 of the final treatment cycle, were interpreted independently by two pathologists. RESULTS: The study was completed by 131 women (87%). The percentage of women with bleeding (mean +/- SD) was 57.2 +/- 3.6% in the 1/5-mg group and 65.8 +/- 4.2% in the 1/10-mg group (p < 0.001); cross-sectional analysis showed that, in every cycle, there were more women with bleeding in the 1/10-than in the 1/5-mg group (p < 0.001). With regard to the day of onset of bleeding, the mean difference between groups was 1.4 +/- 1.1 days (p < 0.001). There was no difference in duration of bleed (5 days), or intensity or incidence of intermittent bleeding (3-14% per cycle). Both regimens resulted in high rates of amenorrhea in each cycle (26-49%), but only 14/151 (9%) women were amenorrheic throughout. Three patients (2%) discontinued owing to bleeding problems. Endometrial protection was adequate in 98.3% (1/5-mg group) and 98.5% (1/10-mg group) with only one case of proliferation (1/10-mg group) and one of simple hyperplasia (1/5-mg group). CONCLUSIONS: The bleeding pattern associated with low-dose (1 mg) estradiol sequentially combined with 5 or 10 mg dydrogesterone shows a high rate of amenorrhea in each cycle; there is a dydrogesterone dose effect on the occurrence and day of onset of bleeding. Bleeding episodes that occur show a regular pattern and are of slight intensity. The endometrial safety of both regimens is high.