MisoREST: surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: a randomized controlled trial.

STUDY QUESTION: Is curettage more effective than expectant management in case of an incomplete evacuation after misoprostol treatment for first trimester miscarriage? SUMMARY ANSWER: Curettage leads to a higher chance of complete evacuation but expectant management is successful in at least 76% of women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. WHAT IS KNOWN ALREADY: In 5-50% of the women treated with misoprostol, there is a suspicion of incomplete evacuation of the uterus on sonography. Although these women generally have minor symptoms, such a finding often leads to additional curettage. STUDY DESIGN, SIZE, DURATION: From June 2012 until July 2014, we conducted a nationwide multicenter randomized controlled trial (RCT). Women who had had primary misoprostol treatment for miscarriage with sonographic evidence of incomplete evacuation of the uterus were randomly allocated to either curettage or expectant management (1:1), using a web-based application. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 59 women in 27 hospitals; 30 were allocated to curettage and 29 were allocated to expectant management. A successful outcome was defined as sonographic finding of an empty uterus 6 weeks after randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics of both groups were comparable. Empty uterus on sonography or uneventful clinical follow-up was seen in 29/30 women (97%) allocated to curettage compared with 22/29 women (76%) allocated to expectant management (RR 1.3, 95% CI 1.03-1.6) with complication rates of 10% versus 10%, respectively (RR 0.97, 95% CI 0.21-4.4). In the group allocated to curettage, no woman required re-curettage, while two women (6.7%) underwent hysteroscopy (for other or unknown reasons). In the women allocated to expectant management, curettage was performed in four women (13.8%) and three women (10.3%) underwent hysteroscopy. LIMITATIONS, REASONS FOR CAUTION: Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely. WIDER IMPLICATIONS OF THE FINDINGS: In women suspected of incomplete evacuation of the uterus after misoprostol, curettage is more effective than expectant management. However, expectant management is equally safe and prevents curettage for most of the women. This finding could further restrain the use of curettage in the treatment of first trimester miscarriage. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3310, http://www.trialregister.nl TRIAL REGISTRATION DATE: 27 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 12 June 2012.

MisoREST: Surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: A cohort study.

OBJECTIVE: To assess the effectiveness of curettage versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. STUDY DESIGN: We conducted a multicenter cohort study alongside a randomized clinical trial (RCT) between June 2012 until July 2014. 27 Dutch hospitals participated. Women with an incomplete evacuation after misoprostol treatment for first trimester miscarriage who declined to participate in the RCT, received treatment of their preference; curettage (n=65) or expectant management (n=132). A successful outcome was defined as an empty uterus on sonography at six weeks or uneventful clinical follow-up. We furthermore assessed complication rate and (re)intervention rate RESULTS: Of the 197 women who declined to participate in the RCT, 65 preferred curettage and 132 expectant management. A successful outcome was observed in 62/65 women (95%) in the surgical group versus 112/132 women (85%) in the expectant group (RR 1.1, 95% CI 1.03-1.2), with complication rates of 6.2% versus 2.3%, respectively (RR 2.7, 95% CI 0.6-12). CONCLUSION: In women with an incomplete evacuation of the uterus after misoprostol treatment, expectant management is an effective and safe option. This finding could restrain the use of curettage in women that have used misoprostol in the treatment of first trimester miscarriage.

Hepatic chemoinfusion of 5-FU in metastasis of gastrointestinal cancer and advanced primary hepatocellular carcinoma.

From 1 January 1983 to 1 January 1988, 38 patients were treated for hepatic cancer in the HEINZ-KALK-Hospital. Thirty-one of these had liver metastases due to gastrointestinal cancer and seven had advanced primary hepatocellular cancer. In all patients more than 50% of the liver volume was involved with the tumour or the metastases. Eleven patients with liver metastases of gastrointestinal cancer (excepting colorectal cancer) were treated by intra-arterial hepatic bolus infusion of 750-1000 mg 5-fluorouracil (5-FU) by selective catheterisation of the hepatic or superior mesenteric artery after puncture of the right or left femoral artery. The median survival was 13.4 months. In seven patients with advanced primary hepatocellular carcinoma the same therapeutic regime was used. The median survival was 10 months. In the 21 patients with disseminated metastases of previously resected colorectal cancer a catheter was inserted into the gastro-duodenal artery and connected to a subcutaneously placed port. Brief infusions of 750-1000 mg 5-FU were administered for 14 days with a day interruption and thereafter 2 month interruption. There were few side effects and 80% of the patients continued to work or carry on a normal life. The median survival was 14.4 months. Based on this experience we consider hepatic chemoinfusion with 5-FU in gastrointestinal cancer and advanced primary hepatocellular carcinoma is capable of improving quality of life and possibly expectancy.

Analysis of a prospective series of 100 mesocaval interposition shunts for bleeding portal hypertension.

The results of a prospective series using the mesocaval interposition shunt (MIS) over a period of 13 years is reviewed. One hundred patients were selected for the operation using strict criteria, and in 98 cases the operation was performed electively. Selection criteria included a liver volume of between 1,000 and 2,500 ml, portal perfusion of between 15-30%, no active liver disease and no stenosis of hepatic artery or celiac axis, as well as a good functional Child-Pugh classification (A-B). In all the cases preoperative sclerotherapy was performed as many times as needed with the aim of controlling the active bleeding at admission and of diminishing the pre- and postoperative bleeding probability. Intra-operative postshunt measurements showed residual portal perfusion in all patients studied. Early mortality was 10% and the follow-up mortality 38.8%. The main causes of death were liver failure and hepatocellular carcinoma. The five- and ten-year survival rates were 65% and 35%, respectively. The total encephalopathy rate was 12.2%. Rebleeding was observed in 5.5% of the cases, and the long term-shunt patency rate was 90%. Anigography and sequential scintigraphy showed residual portal perfusion in 75% of the cases soon after operation, in 60% after 6 months, and in 38% after 2 years, showing the tendency of the diversion to diminish the portal perfusion rate in the late postoperative period. The results show that MIS still has a place in the treatment of portal hypertension and that it is an excellent alternative choice to the selective shunts and the devasculariaztion procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

[The pregnant patient with acute liver disease]. / De zwangere met een acute leverziekte.

Acute liver disease was diagnosed in three pregnant patients: two 30-year-old women had a 'haemolysis, elevated liver enzymes, low platelets' (HELLP) syndrome and acute fatty liver of pregnancy, respectively, and a 20-year-old woman had acute liver failure due to acute hepatitis B. The first two patients had a caesarean section, the third one delivered her child, which died spontaneously shortly after birth at a gestational age of 23 weeks. She was then treated by liver transplantation. All three patients left the hospital in good condition. Liver diseases in pregnancy may be pregnancy-related, e.g. the HELLP syndrome and acute fatty liver of pregnancy, but they may also be coincidental phenomena, e.g. viral hepatitis. The HELLP syndrome is often associated with pre-eclampsia, and presents with epigastric pain and thrombocytopenia with haemolysis. Acute fatty liver disease and acute liver failure due to hepatitis present with liver insufficiency characterised by anorexia, nausea, coagulopathy, hypoglycaemia and elevated serum ammonia levels. Management depends on the diagnosis and the gestational age; pregnancy complicated by acute fatty liver disease should be terminated while pregnancy complicated by the HELLP syndrome early in pregnancy may be maintained to improve the outcome of the foetus. In acute liver failure due to viral hepatitis, termination of pregnancy alone does not affect the disease.

[No major difference between population screening for cervical carcinoma at the present screening interval of 5 years and the former interval of 3 years]. / Geen groot verschil tussen bevolkingsonderzoek op cervixcarcinoom bij het huidige screeningsinterval van 5 en het vorige van 3 jaar.

OBJECTIVE: To assess the effect of extending the screening interval from 3 to 5 years on the detection of premalignant changes and invasive cervical carcinoma in the restructured population screening programme. DESIGN: Retrospective follow-up study. METHOD: The results were collected of the 1st round (1996-2000; 277, 377 women) and a part of the 2nd round (2001; 49,622 women; screening interval: 5 years) of the screening programme in Region West, the Netherlands. Histoscores for cervical intraepithelial neoplasia (CIN) 3 and squamous cell carcinoma (n/100 women investigated) and the hit count (sum of the histoscores for CIN 3, adenocarcinoma in situ and (micro)invasive cervical carcinoma) were calculated. Data of women with adenocarcinoma in situ and endocervical (adeno)carcinoma were recorded separately. The results of the 1st and 2nd round of the current screening programme (commenced in 1996) were compared with those of the historical screening programme that commenced in 1976 (screening interval: 3 years). RESULTS: From the 1st to the 2nd round of the historical screening programme that commenced in 1976, the histoscores for CIN 3 (3.33, 1.88) and squamous cell carcinoma (0.53, 0.19) and the hit count (3.92, 2.15) all diminished significantly. The current restructured programme, which commenced in 1996, showed low starting values for all three parameters, comparable to those in the 2nd round of the 1976 programme; a further reduction (0.16, 0.08; p < 0.01) was seen only in the histoscore for squamous cell carcinoma. In both rounds of both programmes, the histoscores for adenocarcinoma in situ (0.02, 0.02, 0.05, 0.04, respectively) and endocervical adenocarcinoma (0.04, 0.06, 0.05, 0.04) remained stable. CONCLUSION: In the current cervical carcinoma screening programme, with a screening interval of 5 years, the hit count of serious abnormalities remained constant while the incidence of squamous cell carcinoma decreased; this is in contrast to the historical screening programme (commenced in 1976), when both the hit count and the histoscore for CIN 3 diminished significantly. There were indications that cervical screening has no beneficial effect on the prevention of cervical adenocarcinoma.

100 meso-caval interposition-shunts for recurrent variceal hemorrhage in portal hypertension. A prospective study.

The results of a prospective series using the mesocaval interposition shunt (MIS) over a period of 13 years is reviewed: 100 patients were selected for the operation using strict criteria and in 98 cases the operation was performed electively. Selection criteria included liver volume between 1000-2500 mL, portal perfusion between 15-30%, no active liver disease and no stenosis of hepatic artery or coeliac axis as well as a good functional CHILD-PUGH classification (A-B). In all the cases preoperative sclerotherapy was performed so many times as needed by each individual patient with the goal of controlling the active bleeding episodes at admission and of diminishing the pre and postoperative bleeding probability. Intraoperative postshunt measurements showed residual portal perfusion in all studied patients. Early mortality was 10% and the follow up mortality 38.8%. Main causes of death were liver failure and hepatocellular carcinoma. Five and ten years survival rates were 63.9% and 35.1% respectively. The total encephalopathy rate was 12.2%. Rebleeding was observed in 5.5% of the cases and long term shunt patency rate among survivors was 90%. Angiography and sequential scintigraphy showed residual portal perfusion in 75% of cases soon after operation, in 60% after 6 months and 38% after 2 years, showing the tendency of the derivation to diminish the portal perfusion rate in the late postoperative period. The results show that MIS still has a place in the treatment of portal hypertension and that it is an excellent alternative choice to the selective shunts and the devascularization procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Progress in the diagnosis of gastroesophageal reflux in childhood: 24-hour pH monitoring.

Twenty-four-hour pH monitoring is a reliable and secure method for use in the diagnosis of gastroesophageal reflux (GER). Compared with other methods, this technique is well tolerated and without complications. In contrast to other techniques (cineradiography, manometry, scintiscanning, endoscopy), long-term pH monitoring is the only method to measure the dynamics in the distal esophagus under nearly physiological conditions and to register the data obtained via pen writer for any time desired. Thus, 24-h pH monitoring is the most sensitive and expressive method for the diagnosis of GER in childhood, providing more secure operative indications combined with other methods.

Long-term endoscopic injection sclerotherapy of bleeding esophageal varices. A prospective analysis of results by endoscopy, manometry and 24-h pH-monitoring.

From 1 January 1986 to 1 January 1988, 91 consecutive patients who had undergone repeated paravariceal endoscopic injection sclerotherapy (PEIS) for bleeding esophageal varices over a period of up to 10 years were followed up prospectively by endoscopy, manometry and 24-h pH monitoring. In 39% nonfatal complications occurred after two phases of PEIS. The number of complications tended to decrease with increasing phases and was only 12% after five or more phases of PEIS. Endoscopy is undoubtedly the most important method in the follow-up of these patients. Early and long-term complications are mostly diagnosed by direct view and thus can be managed or sometimes even prevented in the follow-up. No significant motility disorders were found. Only 12 patients showed significant gastroesophageal reflux. No correlation was found between the severity of reflux and the number of phases of PEIS. No correlation between clinical symptoms and changes in the manometric and pH metric results could be found. The effects and side effects of PEIS can be closely monitored by manometry and pH monitoring and therapy can be tailored accordingly. Our results suggest that PEIS is a superb method with a low complication rate, both short- and long-term. It has proven to be an effective long-term treatment of bleeding esophageal varices.

Improved results with selective distal splenorenal shunt in a highly selected patient population. A prospective study.

In a 5-year period 299 patients were admitted to the Heinz-Kalk Hospital with bleeding esophageal varices. Patients with acute bleeding were treated with endoscopic sclerotherapy. Sessions were performed as many times as needed for each individual case. One hundred seventy-eight patients in Child-Pugh class C were excluded from surgical treatment; the remaining 121 patients (Child AB) were selected using the following criteria: liver volume (ultrasound) between 1000 to 2500 ml, portal perfusion (sequential scintigraphy) more than 30%, no activity or progression of liver disease proved by biopsy, no stenosis of the hepatic arteries, and suitable anatomy to perform the Warren shunt. Only 32 patients fulfilled these criteria. In seven of these cases the shunt was technically impossible to perform. Operative mortality rate was 8% and the late mortality rate was 12%. No history of rebleeding, encephalopathy, and/or shunt thrombosis was recorded. Five-year survival rate, according to the method of Kaplan-Meier was 75%. We conclude that the Warren shunt is the treatment of choice for elective management of bleeding esophageal varices. The postoperative results can be improved with strict selection using the above criteria. The preoperative use of sclerotherapy has a positive influence. Prophylactic management to prevent encephalopathy is also recommended.