Marie Granowska

Disturbed gastric and small bowel transit in severe idiopathic constipation

Many patients with severe idiopathic constipation complain of upper gastrointestinal symptoms, and these often persist after subtotal colectomy. To determine if there is a disturbance of upper gastrointestinal motility in this condition, we have studied gastric emptying for solids (111In-containing pancake) and liquids (99mTc-containing orange, juice) for a longer period after a meal (6 hr) than in previously reported gastric emptying studies. Small bowel transit for solids was also measured. All patients had emptied their colon the day before the study. Twelve women (mean age 36 years) with a bowel frequency of less than once per week, proven slow intestinal transit, and a normal diameter colon were studied. Twelve healthy controls (eight female and four male, mean age 33) were also studied. As a group the constipated patients demonstrated no statistically significant delay in emptying during the first 3 hr, although the emptying rate for three of 12 individuals fell outside the normal range. However, at 6 hr after ingestion of the meal, six of 10 patients had residual gastric contents greater than normal-up to 48% solid residue (median: 11% for patients and 0% for controls,P<0.01) and 40% of liquid (median 9% vs 0%P<0.01). Three of four patients with upper gastrointestinal symptoms 6 hr after the meal had gastric retention of solids markedly outside the normal range (48%, 32%, and 16%; normal<4%). Small bowel transit time was assessed as the time for the solid phase to pass from the duodenum to the cecum; the constipated patients demonstrated delayed transit (median: 75 vs 55 min,P<0.01). Effectiveness of small bowel transit was assessed by the proportion of solids in the cecum at the time the stomach had emptied 50% of the solid meal; this was reduced in the patients (median: 6 vs 18%,P<0.01). All patients with normal gastric emptying had normal small bowel transit, and all those with delayed gastric emptying had prolonged small bowel transit. Colonic transit of the radioisotope was slow in all patients (head of the radioisotope column, cecum to stool, median: 96 vs 31 hr,P<0.01). Many patients with severe idiopathic constipation have a disturbance of gastric and small bowel transit that may be related to symptoms and that have implications for treatment.

Tumour-associated monoclonal antibodies for the diagnosis and assessment of ovarian cancer.

Summary. A tumour‐associated radiolabelled monoclonal antibody (HMFG 2) was used to investigate 51 patients who were referred with a pelvic mass and suspected ovarian cancer or recurrent disease. The day before operation the 123I‐labelled antibody was injected and the patients then underwent radioimmunoscintigraphy immediately and again 4 and 22 h after the injection. An exploratory laparotomy with appropriate surgery was then performed and the tumours were staged. Tumours were positively imaged 3 min‐22 h after injection in all the patients with ovarian cancer, with a mean 0.6% of the injected antibody taken up by the tumour. The presence of HMFG antigen on the tumour was confirmed by immunoperoxidase staining of the surgically‐removed tissues. Of the 51 patients, 39 proved to have ovarian cancer. The accuracy of diagnosis and detection of primary and metastatic malignant disease was 95% when correlating pre‐operative radioimmune scan findings and laparotomy findings. The procedure is minimally invasive, apparently without side‐effects and offers information for tumour detection as an adjunct or alternative to existing methods.

Prostate cancer: the contribution of nuclear medicine

For many years the main uses of nuclear medicine in the management of prostate cancer were to check for bone metastases by whole-body imaging, using an agent such as Tc-methylene diphosphonate, or to assess renal function. This review concentrates on the progress towards the speci®c imaging of prostate cancer, including its capsular extension, local nodal involvement, and staging before considering primary prostatic cancer surgery. Prostate cancer-speci®c imaging for determining recurrence of disease, particularly when the PSA level increases and the bone scan and radiology are not informative, will also be reviewed. Direct imaging of prostate cancer had a long and relatively unrewarding history until recently. The prostate contains zinc and early attempts using radionuclides of zinc were largely unsuccessful [1,2]. Radiolabelled sex-hormone analogues have been tried in many forms, with little success, e.g. Br-DHT [3], IDHT [4], ̄uoromibolerone [5] and androgens [6,7]. An alternative approach has been to use analogues of amino acids such as Se-selenomethionine [8], C-ornithine [9] and F-putrescine [10]. F-Deoxyglucose, an analogue of glucose which is generally absorbed by cancers more than by benign disease, but also by in ̄ammatory cells, is imaged using PET, with variable results. Effert et al. [11] failed to differentiate between BPH in 16 patients and carcinoma in 48 patients using this technique, and others have reported varying success [12±15]. Pelvic lymphoscintigraphy has been attempted for assessing lymphatic drainage from the prostate. Methods included transrectal injection with Tc-antimony sulphide colloid [16,17], or phytate and colloid [18], into the prostatic capsule. Experimental studies in the dog and in humans using Tc-colloid [19] have failed to establish a routine clinical role in the staging of prostate cancer.

Radioimmunoscintigraphy of orbital metastases from ovarian carcinoma

Radioimmunoscintigraphy with I-123 labeled monoclonal antibody HMFG1 has been used for imaging primary and metastatic ovarian neoplasms. Uptake of I-123 labeled HMFG1 is reported in a patient with an orbital metastasis from a primary ovarian adenocarcinoma. Radioimmunoscintigraphy may have a role to play in imaging metastatic orbital neoplasms.

Monoclonal antibodies and their usefulness in epithelial ovarian cancer. A review

In epithelial ovarian cancer, monoclonal antibodies are used in vitro in the histological and cytological diagnosis of tumours, and in serial measurements of serum tumour markers to aid the clinical management of patients. In vivo, they are being used routinely in the radioimmunolocalization of tumour deposits (radioimmunoscintigraphy) and, more recently in their treatment (radioimmunotherapy)

Immunoscintigraphy of Ovarian Cancer by Means of HMFG2 Monoclonal Antibody

Human milk fat globule 2 (HMFG2) antibody is a monoclonal antibody, class IgG1, against the HMFG protein, which is a large glycoprotein (300 KD). It is present on the epithelial surface membrane lining of the duct of the breast, the crypts of the colon, and the inside lining of ovarian follicles [1, 2].

Efficacy of immunoscintigraphy for detection of lymph node metastases.

The size of a lymph node is not in principle a limitation for the detection of cancer by Nuclear Medicine techniques. A radioactive pinhead is detectable if it has enough radioactivity on it. The approach of Nuclear Medicine to the demonstration of impalpable lymph nodes or to those lymph nodes detected by radiological techniques that are under 1 cm as to whether or not they contain cancer, is to increase the activity attached to cancer cells in such a lymph node as much as possible and to use sophisticated image analysis techniques to distinguish such uptake from its environment. This may be undertaken using a non specific technique such as F-18 Deoxyglucose and Positron Emission Tomography which is highly sensitive and which has been successful. The alternative approach is to use a highly specific and sensitive agent, such as a radio-labelled peptide or a radio-labelled monoclonal antibody together with image analysis. This paper describes these approaches and in particular the use of Tc-99m SM3 monoclonal antibody in the detection of impalpable axillary nodes in patients with breast cancer before surgery, using a change detection analysis providing a probability map of the significance of uptake of this radiopharmaceutical. It is a robust approach, providing the patient and the surgeon with information as to the likely need for extensive axillary surgery well prior to operation. A negative study should be followed by a sentinel node evaluation at surgery.

Prostate cancer: clinical questions and imaging answers

Prostate cancer is now the commonest cancer in humans and the third commonest cancer after breast and lung cancer; both the frequency and incidence are increasing. The three main clinical questions are: (1) What is the extent of prostate cancer when radical surgery is proposed? (2) Where is the disease when there is a rising PSA and a normal bone scan and radiology? (3) What is the significance of a PSA which is in the normal range but non-zero after radical prostatectomy or radical radiotherapy? Staging is important. The prognosis falls from 80% five-year survival to 30% five-year survival if a single node is involved with prostate cancer. The imaging questions therefore are: (1) Is the prostate capsule breached? (2) Is there local node involvement? (3) Is there extra pelvic node involvement? (4) Is the skeleton involved? The last question is usually answered with the methylene diphosphonate (Tc-99m MDP) bone scan. A recently positive bone scan will reflect the presence of metastases, whereas a persistently positive bone scan may represent the healing process continuing and the effect of hormonal therapy, rather than persistence of active metastases. Painful bone metastases may be treated using Strontium 89, or Sm-153 EHMDP radionuclide therapy[1].

Experience with Iodine-123 Labeled Antibodies

In order to image the distribution of spread of metastases from a primary adenocarcinoma in a patient using radioimmunoscintigraphy, a combination of four factors is required: an antibody specific to the cancer in question; a radiolabel that is optimal for the imaging system and for the kinetics of antibody uptake; a method of labeling the antibody and quality control so that is is suitable for injection into the patient; and, a gamma camera imaging system that enables the distribution of the radiolabeled antibody to be visualized to the best advantage. Although it is evident that the major limitation of the current practice of radioimmunoscintigraphy is the inability to get sufficient numbers of a sufficiently specific antibody on to all the cancer cells that have spread from the primary site, this paper is concerned with the other three requirements: the radiolabel, the labeling method, and the imaging of its distribution, with particular reference to the use of iodine-123.