The effectiveness of immediate versus delayed tubal flushing with oil-based contrast in women with unexplained infertility (H2Oil-timing study): study protocol of a randomized controlled trial.

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. METHODS: This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated. DISCUSSION: The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice. TRIAL REGISTRATION NUMBER: The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).

Oil-based versus water-based contrast media for hysterosalpingography in infertile women of advanced age, with ovulation disorders or a high risk for tubal pathology: study protocol of a randomized controlled trial (H2Oil2 study).

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography (HSG) increases ongoing pregnancy and subsequent live birth rates when compared to tubal flushing with water-based contrast. It is currently unclear whether an HSG with oil-based contrast also results in more ongoing pregnancies and live births in women of advanced age, women with ovulation disorders, and women with potential tubal pathology when compared to an HSG with water-based contrast. METHODS: We plan an international, multicentre, open-label, randomized controlled trial (RCT) studying three groups of infertile women who have an indication for tubal patency testing according to their treating physician and additionally; (1) are 39 years of age or older, (2) have an ovulation disorder or (3) have a high risk for tubal pathology based on their medical history. Women with an allergy for iodinated contrast medium are excluded, as are women with diabetes, hyperprolactinemia or untreated hyper- or hypothyroidism, and women with a partner with severe male infertility. After informed consent, women will be randomly allocated to the intervention, tubal flushing with the use of oil-based contrast during HSG or the control group, tubal flushing with the use of water-based contrast during HSG in a 1:1 ratio by the web-based system Castor. The primary endpoint will be ongoing pregnancy leading to live birth with conception within six months after randomization. Secondary outcomes are other pregnancy outcomes, used fertility treatments, adverse events and cost-effectiveness. Based on the expected ongoing pregnancy rate of 17% in the control group and 27% in the intervention group, the sample size will be 930 women (465 per group). Study inclusion is expected to be complete in four years. DISCUSSION: This multicentre RCT will establish whether, for women of advanced age, women with ovulatory disease, and women who have a high risk for tubal pathology, there is a fertility enhancing effect of tubal flushing with oil-based contrast during HSG and whether the use of this contrast medium is cost-effective. Trial Registration The study was prospectively registered in the Netherlands Trial Register on August 1st 2019 as 'H2Oil2' (reference number NL7925, https://www.trialregister.nl/trial/7925 ).

Changes in muscle strength and pain in response to surgical repair of posterior abdominal wall disruption followed by rehabilitation.

BACKGROUND: Posterior abdominal wall deficiency (PAWD) is a tear in the external oblique aponeurosis or the conjoint tendon causing a posterior wall defect at the medial end of the inguinal canal. It is often known as sportsman's hernia and is believed to be caused by repetitive stress. OBJECTIVE: To assess lower limb and abdominal muscle strength of patients with PAWD before intervention compared with matched controls; to evaluate any changes following surgical repair and rehabilitation. METHODS: Sixteen subjects were assessed using a questionnaire, isokinetic testing of the lower limb strength, and pressure biofeedback testing of the abdominals. After surgery and a six week rehabilitation programme, the subjects were re-evaluated. A control group were assessed using the same procedure. RESULTS: Quadriceps and hamstrings strength was not affected by this condition. A deficit hip muscle strength was found on the affected limb before surgery, which was significant for the hip flexors (p = 0.05). Before surgery, 87% of the patients compared with 20% of the controls failed the abdominal obliques test. Both the injured and non-injured sides had improved significantly in strength after surgery and rehabilitation. The strength of the abdominal obliques showed the most significant improvement over the course of the rehabilitation programme. CONCLUSIONS: Lower limb muscle strength may have been reduced as the result of disuse atrophy or pain inhibition. Abdominal oblique strength was deficient in the injured patients and this compromises rotational control of the pelvis. More sensitive investigations (such as electromyography) are needed to assess the link between abdominal oblique function and groin injury.

Interventional radiology in palliative medicine.

Substantial developments in interventional radiology over the last two decades have resulted in the introduction of new methods of treatment for patients with advanced malignancy. These new minimally invasive techniques avoid the need for prolonged hospital inpatient care.

Superior vena caval obstruction managed by the Gianturco Z Stent.

Twenty patients with superior vena caval obstruction (SVCO) due to malignancy were managed using the Gianturco Z Stent. Three patients had adjunctive thrombolysis. The primary clinical success was 90% (18/20 patients). Thirteen patients were free of SVCO to death or follow-up without re-intervention (primary patency = 65%). Three patients had re-intervention for recurrent symptoms, two successfully (secondary long-term patency = 75%). Stenting of the SVC is a valuable, under-used technique for the symptomatic relief of superior vena caval obstruction.

Malignant 'angiodysplasia'.

Four patients with chronic gastrointestinal blood loss of obscure aetiology were investigated by visceral angiography. All showed angiographic abnormalities in the caecum with characteristic features seen in angiodysplasia as well as other conditions such as inflammatory bowel disease, carcinoma. All four patients had a malignant cause for their angiographic appearance. This paper stresses the importance of reviewing previous examinations before accepting a diagnosis of angiodysplasia. The angiographic features of contrast pooling on the anti-mesenteric border of the caecum or ascending colon, a dilated intramural vein and early filling of a draining vein imply that serious pathology is present.

Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase.

Twenty-seven patients with brain glioma were scanned using 123I-labeled monoclonal antibodies against epidermal growth factor receptor (EGFR1) or placental alkaline phosphatase (H17E2). Successful localization was achieved in 18 out of 27 patients. Eleven out of 27 patients were also studied using a nonspecific control antibody (11.4.1) of the same immunoglobulin subclass and observable tumor localization was also achieved in five patients. The specificity of targeting was assessed by comparing images obtained with specific and nonspecific antibodies and by examining tumor and normal tissue biopsies after dual antibody administration. Ten patients with recurrent grade III or IV glioma who showed good localization of radiolabeled antibody were treated with 40-140 mCi of 131I-labeled antibody delivered to the tumor area intravenously (n = 5) or by infusion into the internal carotid artery (n = 5). Six patients showed clinical improvement lasting from 6 mo to 3 yr. One patient continues in remission (3 yr after therapy), but the other five who responded initially relapsed 6-9 mo after therapy and died. No major toxicity was attributable to antibody-guided irradiation. Targeted irradiation by monoclonal antibody may be clinically useful and should be explored further in the treatment of brain gliomas resistant to conventional forms of treatment.

Percutaneous transluminal angioplasty of the distal abdominal aorta.

Percutaneous Transluminal Angioplasty (PTA) has become widely practised and is a significant advance in the treatment of arterial disease. Its use in the treatment of atheromatous abdominal aortic stenoses in thirteen patients is described. Technical success was achieved in all with no complications. In a follow-up period from 7 to 70 months all patients have benefitted and 85% remain symptom free.

Angiodysplasia as a cause of iron deficiency anaemia.

Angiodysplasia, a condition of unknown aetiology, is thought to represent the commonest cause of obscure gastrointestinal bleeding, particularly in the elderly population. The lesions of angiodysplasia, which are small (less than 5 mm) and usually multiple, consist of microvascular abnormalities in the mucosa and submucosa of the bowel wall. They are most commonly found in the caecum and right side of the colon, but have been observed in the stomach, ileum and elsewhere in the colon. The diagnosis is made by either selective visceral angiography and/or colonoscopy, but the lesions cannot be detected on barium studies or with the naked eye at laparotomy. Localisation of the abnormalities by the histopathologist is greatly facilitated by special injection techniques demonstrating the blood vessels of resected colonic specimens prior to fixation and section. Treatment may be conservative (iron replacement) if the anaemia is not severe, by endoscopic fulguration or by colonic resection. Other common causes of gastrointestinal blood loss should always be excluded before the final diagnosis of angiodysplasia is accepted. Although the condition is well recognised as a significant cause of gastrointestinal blood loss a number of questions remain to be answered. The true incidence of angiodysplasia in the population is not known, the aetiology of the condition remains a mystery, although many theories abound.

Hemobilia. A disease in evolution.

Ten patients with hemobilia were treated over a six-year period. Six cases resulted from iatrogenic injury (percutaneous invasive procedures, four; surgical trauma, two); the others were caused by gallstone disease (two), liver trauma (one), and vasculitis (one). Five patients were treated successfully by selective arterial embolization. In the other five patients, embolization was not possible due to previous surgical and/or radiologic procedures, or it was contraindicated, and thus, surgical treatment was undertaken. One of these patients died. There were no long-term sequelae in the remaining nine patients followed up for 12 to 66 months. Selective hepatic arterial embolization is the treatment of choice for hemobilia. Inappropriate embolization or surgery frequently fails to control the bleeding and may also prevent later successful embolization.

Complications of embolization: analysis of 410 procedures.

Over a 10-year period, 284 patients underwent 410 embolization procedures because of liver, renal, or bone tumors; gastrointestinal bleeding; systemic or pulmonary arteriovenous malformations; and other miscellaneous lesions. A wide range of particulate and liquid embolic agents were used. The complications were analyzed with respect to the patient's underlying abnormality. Minor complications occurred after 16.3% of procedures, serious complications after 6.6%, and death after 2%. The postembolization syndrome (fever, elevated white blood cell count, and discomfort) was encountered after 42.7% of the procedures, and in 43.7%, no significant adverse reactions were documented. The major complications and deaths were encountered in patients with a serious underlying abnormality in whom no alternative form of treatment was available and who were extremely sick prior to the procedure. When considered in relationship to the natural progress of the disease and the lack of other treatment options, the overall complication rate seems acceptable.

Gastrointestinal haemorrhage from a second source in patients with colonic angiodysplasia.

Angiodysplasia of the colon is increasingly recognized as a cause of obscure gastrointestinal haemorrhage. On review of 71 patients with angiodysplasia, 40 came to surgery. Of these, nine (22.5 per cent) were also found to have small bowel lesions, either at the original laparotomy (7) or later when further investigations were performed for recurrent bleeding. Angiodysplasia can only be confidently diagnosed as the source of blood loss if seen to be actively bleeding. If a synchronous small bowel lesion is seen, we recommend that it should be removed at the same time as the colectomy.

Specialist investigation of obscure gastrointestinal bleeding.

The investigation and treatment of 131 patients with 'obscure' gastrointestinal bleeding has been reviewed. One hundred and six patients were assessed electively for recurrent haemorrhage, 25 presented as emergencies. The major presenting feature was melaena (55 patients), anaemia (35), rectal bleeding (34), haematemesis (six) and ileostomy bleeding (one). The lesions responsible for haemorrhage were colonic angiodysplasia (52 patients), small bowel vascular anomalies (16), Meckel's diverticula (nine), small bowel smooth muscle tumours (seven), gastric vascular anomalies (four), chronic pancreatitis (three), colonic diverticular disease (three) and 16 other miscellaneous lesions. No lesion was found in 21 cases. Lesions were first shown by visceral angiography (69 patients), at laparotomy (23), on endoscopy (11), on gastrointestinal contrast radiological studies (four), and at ERCP (three). Lesions which were undetectable at operation increased markedly with age (p less than 0.0001). Expert visceral angiography is strongly recommended before surgery in patients over 45 years of age and after laparotomy when no cause has been found. Exploratory laparotomy is recommended at an early stage for younger patients, and for older patients after non-diagnostic angiography.

The radiology of fibrolamellar hepatoma.

Seven patients with fibrolamellar hepatoma were examined with computed tomography (CT), ultrasonography and angiography. On CT the tumours were large, of low attenuation, had a well-defined edge and some contained areas of calcification or necrosis. Ultrasonography revealed well-defined masses of mixed echogenicity, occasionally involving the portal vein. In one patient there was dilatation of the intrahepatic biliary tree. Arteriography showed vascular tumours with involvement of the portal vein in five cases and compression of the inferior vena cava in five cases. CT and ultrasonography are the most useful radiological investigations for suggesting the diagnosis of fibrolamellar hepatoma which should be considered in the case of any large solitary well-defined hepatic tumour in the noncirrhotic liver of a young person.

Bile duct obstruction: radiologic evaluation of level, cause, and tumor resectability.

In a prospective study of 65 patients with bile duct obstruction, various radiologic modalities were compared for their capability to demonstrate the level and cause of obstruction and to indicate accurately tumor resectability. Ultrasound (US) was performed in 65 patients, computed tomography (CT) in 51, direct cholangiography (DC) in 57, and angiography in 35. The level of obstruction was correctly indicated by US in 95% of patients and by CT in 90%, and the cause was correctly indicated by US in 88%, by CT in 63%, and by DC in 89%. In predicting tumor resectability, US was correct in 71% of patients, compared with 42% for CT, 58% for DC, and 25% for angiography. US therefore appears to be the single most useful modality in the evaluation bile duct obstruction.

Functioning middle mediastinal paraganglioma (phaeochromocytoma) associated with intercarotid paragangliomas.

In three patients with phaeochromocytomas, computed tomography or iodobenzylguanidine scanning gave misleading or negative results. These patients were found to have a functioning middle mediastinal paraganglioma in association with one or two intercarotid paragangliomas. The possibility of this association should be considered in patients with functioning extra-adrenal paragangliomas.

Liver lobe disparity consequent upon atrophy. Diagnostic, operative and therapeutic considerations.

Liver lobe disparity consequent upon lobar atrophy with compensatory hypertrophy of the contralateral lobe is a pathological entity usually encountered with high bile duct obstruction and is associated with particular diagnostic and operative problems, discussed here by reference to 10 patients. The hypertrophied lobe presented as an abdominal 'mass' in all 10 whilst the atrophied lobe imitated a 'cold' area on liver scintigraphy and was misinterpreted as a tumour in 2 cases. The operative difficulties, exemplified by 8 patients, arise from the distortion of the configuration of the liver, the alteration of the anatomical relations of the vascular and biliary structures, and the reduced functional capacity of the atrophied liver. Pre-operative diagnosis of the condition is important to allow optimal treatment.

The pre-operative embolisation of vascular malformations.

Large arteriovenous malformations frequently require surgical excision in order to prevent or treat the potentially serious problems they can cause ranging from haemorrhage and pain to cardiac failure. The surgery itself is usually difficult and often dangerous due to the serious risk of major intraoperative haemorrhage. Transcatheter arterial embolisation has greatly facilitated the management of small arteriovenous malformations but may only afford temporary relief of symptoms in very large lesions. Recanalisation of occluded vessels and revascularisation via previously insignificant collateral vessels means that large lesions cannot be effectively managed by this method alone. Previous surgery and ligation of feeding vessels may make effective embolisation difficult or impossible and a combined radiological and surgical approach to these lesions may permit definitive treatment. We present three cases in whom the pre-operative embolisation of buttock arteriovenous malformations facilitated successful surgical excision.