IgA nephropathy in association with Crohn's disease.

BACKGROUND: Urological complications of inflammatory bowel disease are seen in up to 25% of patients, but renal parenchymal disease is rarely reported. CASE REPORT: The authors describe a case of a 29-year-old man with clinical and radiological features of ileocaecal Crohn's disease. He had previously been investigated for painless macroscopic haematuria and a renal biopsy had revealed IgA nephropathy. Despite medical treatment, regular exacerbations of Crohn's disease were associated with deterioration in renal function and the development of haematuria. The patient eventually underwent surgical resection of the terminal ileum and caecum. His renal disease has remained quiescent for the last 5 years following resection.

Peri-operative radiotherapy for rectal cancer: the case for a selective pre-operative approach - the third way.

Peri-operative radiotherapy has been used widely in addition to surgery in an attempt to reduce local recurrence (LR) following surgical resection of rectal cancer. Currently different groups follow different approaches with some routinely administering one weeks pre-operative radiotherapy to all cases of operable mobile cancer with others favouring postoperative chemoradiotherapy for selected high risk groups. In this review we bring together the changes in surgery, pathology and imaging that have occurred in recent years and together with the data from recent randomized pre-operative radiotherapy trials propose a logical and optimal way of managing rectal cancer. This third way is selective and pre-operative and should ensure a low rate of LR with radiotherapy reserved for those cases that need it.

Protective role of lactulose in intestinal carcinogenesis.

Primary bile acids are converted to carcinogenic secondary bile acids by colonic bacteria when the colonic pH is high. Therefore acidification of the luminal contents may reduce the cancer risk. The ability of lactulose to reduce colonic pH, secondary bile acid production, mucosa crypt cell production rate and tumour formation was measured in a rat model of intestinal carcinogenesis. Eighty Wistar rats were divided into four groups receiving normal diet alone or with lactulose, azoxymethane or both azoxymethane and lactulose. The addition of lactulose was associated with a significant fall in small intestinal and colonic pH. Lactulose was associated with a sharp rise in the secondary to primary bile acid ratio. The crypt cell production rate fell significantly with lactulose. The addition of lactulose was associated with a significantly reduced tumour yield in small intestine but not in colon. Lactulose therefore can reduce this is of no value in humans at risk of developing colorectal carcinoma.

The influence of fibroblasts on the growth of human colorectal carcinoma xenografts.

Colorectal carcinoma xenografts were grown in nude mice by inoculation with and without fibroblasts. A significantly greater proportion of tumours grew in mice receiving carcinoma cells with fibroblasts (83% compared to 52%). Tumour weight and thymidine DNA labelling were not significantly different. Initial development but not subsequent growth of xenografts was enhanced by fibroblasts.

Duration of blood flow reduction to normal liver tissue induced by angiotensin, vasopressin and endothelin.

Cytotoxic drug uptake into tumour tissue depends on blood flow. Flow can be diverted to tumour by vasoconstrictors but the effect is temporary whereas prolonged exposure is required. The relative drug uptake advantage depends on the relative tumour blood flow compared to normal tissue. Blood flow to normal liver therefore is an important factor in dose-limiting uptake into normal tissue. Regional drug infusion must match vasoconstrictor action. This was measured by laser doppler flowmetry. The median duration of action was 4.2 minutes for angiotensin, 8.6 for vasopressin and 20.7 for endothelin. Therefore the cytotoxic agent could be infused for the same period repeatedly to reduce toxicity. The flux fall was 33% for angiotensin, 22% for vasopressin and 16% for endothelin. The area below the flux line was 104% minutes for angiotensin, 193% for vasopressin and 335% for endothelin. To increase cytotoxic drug uptake, the cytotoxic drug infusion should be infused intermittently for the duration that the vasoconstrictor is active. As the area under the curve is greatest for endothelin this may be the agent of choice.

Prognostic value of nucleolar organizer regions in colorectal neoplasia.

The aims of the study were, firstly, to determine the frequency of nucleolar organizer regions (NORs) in normal colonic mucosa, adenomas and carcinomas, secondly, to determine the relationship of NOR frequency to adenoma diameter, carcinoma stage, patient survival and tumour recurrence. NOR frequency was determined in invasive carcinoma and adjacent normal mucosa in resection specimens from 46 patients with colorectal carcinoma and in 15 colorectal adenomas obtained at colonoscopy. NOR frequency was correlated with conventional prognostic criteria: adenoma diameter and carcinoma stage, tumour recurrence and patient survival. NOR frequency was significantly (P = 0.02) greater in carcinoma (median = 3.64) and adenoma (median = 2.30) compared to non-neoplastic mucosa (median = 1.96). NOR frequency was not significantly related to adenoma diameter, carcinoma node status, patient survival or tumour recurrence. NOR frequency increases with progression through adenoma to carcinoma. The poor association with conventional prognostic factors suggests that NOR frequency is of no value in prediction of adenoma or carcinoma behaviour and therefore does not closely reflect factors determining malignant cell behaviour.

Histamine but neither angiotensin nor vasopressin increases antibody uptake into xenograft colorectal liver metastases.

Although the majority of colorectal carcinomas express carcino-embryonic antigen (CEA), systemic anti-CEA antibody administration is an ineffective treatment for colorectal liver metastasis. A xenograft model of human colorectal carcinoma in the rat was used to determine anti-CEA antibody uptake into liver metastases. The influence of systemic (iliolumbar vein) or regional (gastroduodenal artery) delivery and effects of regional delivery of histamine, angiotensin II and vasopressin on anti-CEA antibody uptake by metastases were examined. Systemic antibody delivery achieved a median tumour:liver antibody uptake ratio of 1.60 (interquartile range (i.q.r.) 1.02-2.51). Regional delivery resulted in a similar median ratio of 1.61 (i.q.r. 1.22-2.46). Histamine and antibody delivered regionally produced a median tumour:liver ratio of 3.15 (i.q.r. 2.50-4.27), which was significantly greater than that obtained with systemic delivery (P = 0.004). Regional infusion of angiotensin resulted in a median (i.q.r.) ratio of 2.23 (1.58-2.49) and vasopressin in 2.15 (1.41-2.60), values that were not significantly different from those found with systemic or regional delivery alone. When both angiotensin and histamine were infused with antibody, the median tumour:liver ratio was 3.09 (i.q.r. 2.22-4.31), significantly greater than for systemic delivery (P = 0.01) but not significantly different from that obtained following the addition of histamine alone (P = 0.94). Histamine significantly increases antibody uptake in a model of liver metastasis and may improve the effectiveness of targeted immunotherapy in the treatment of colorectal liver metastasis.

Is liver to lung shunting in colorectal liver metastasis the cause of toxicity following treatment with cytotoxic microsphere aggregates?

Incorporation of cytotoxic drugs into microspheres reduces but does not eliminate systemic toxicity. The extent of liver to lung shunt was measured in 26 patients with colorectal liver metastasis. Liver to lung shunting correlated with proportion of liver replacement but did not exceed 4.4% and therefore is unlikely to cause systemic toxicity.

Histamine, leukotriene C4 and interleukin-2 increase antibody uptake into a human carcinoma xenograft model.

Systemically administered radiolabelled anti-tumour antibody is ineffective in treating the majority of patients with liver metastasis from colorectal carcinoma. We have assessed whether agents which increase capillary permeability can increase tumour uptake of antibody isotope conjugate. We developed a xenograft model of colorectal carcinoma using an antibody directed against carcinoembryonic antigen (CEA). Tumours were grown subcutaneously in the hind limbs of athymic rats to derive their circulation from the femoral artery. Cannulae were placed in the common iliac artery and iliolumbar vein. Antibody was delivered systemically, regionally and regionally with histamine, leukotriene C4 and interleukin-2. Regionally administered anti-CEA antibody resulted in a significantly greater (P = 0.004) tumour to normal tissue ratio (1.66, s.d. = 0.68) compared to systematically administered antibody (1.25, s.d. = 0.73). The addition of vasoactive drugs produced an approximately 3-fold increase with an increase to a mean tumour:liver ratio of 3.24 (s.d. = 1.39) for histamine (P less than 0.001 compared to systemic delivery), 3.21 (s.d. = 1.13, P less than 0.001) for leukotriene C4 and 3.80 (s.d. = 1.53, P less than 0.001) for interleukin-2. The addition of histamine significantly (P = 0.004) increased the mean tumour to liver ratio (1.73, s.d. = 0.44) of non-specific antibody uptake compared with either systemic (1.12, s.d. = 0.24) or regional delivery (1.25, s.d. = 0.54) of non-specific antibody alone. Increasing tumour capillary permeability can produce a significant clinically useful increase in tumour uptake of antibody-isotope conjugate.

Rectal examination in general practice.

OBJECTIVE: To investigate factors influencing a general practitioner's decision to do a rectal examination in patients with anorectal or urinary symptoms. DESIGN: Postal questionnaire survey. SETTING: General practices in inner London and Devon. SUBJECTS: 859 General practitioners, 609 (71%) of whom returned the questionnaire. MAIN OUTCOME MEASURES: Number of rectal examinations done each month; the indication score, derived from answers to a question asking whether the respondent would do a rectal examination for various symptoms; and the confidence score, which indicated the respondent's confidence in the diagnosis made on rectal examination. RESULTS: 279 General practitioners did five or fewer rectal examinations each month and 96 did more than 10 each month. Factors significantly associated with doing fewer rectal examinations were a small partnership and being a female general practitioner, and the expectation that the examination would be repeated. Lack of time in the surgery, and a waiting time of less than two weeks for an urgent outpatient appointment were also important. General practitioners were deterred from doing rectal examinations by reluctance of the patient (278), the expectation that the examination would be repeated (141), and lack of time (123) or a chaperone (39). Confidence in diagnosis was significantly associated with doing more rectal examinations, the perception of having been well taught to do a rectal examination at medical school, and being a male general practitioner. CONCLUSIONS: Factors other than clinical judgment influence the frequency of rectal examination in general practice. Rectal examination may become commoner with the trend towards larger group practices and if diagnostic confidence is increased and greater emphasis put on rectal examination in undergraduate and postgraduate teaching.