Transport of Iodine Is Different in Cartilage and Meniscus.

Contrast enhanced computed tomography (CECT) has been proposed for diagnostics of cartilage and meniscus injuries and degeneration. As both tissues may be imaged simultaneously, CECT could provide a method for comprehensive evaluation of knee joint health. Since the composition and structure of cartilage and meniscus are different, we hypothesize that transport characteristics of anionic contrast agents also differ between the tissues. This would affect interpretation of CECT images and warrants investigation. To clarify this, we aimed to determine the transport kinematics of anionic iodine (q = -1, M = 126.9 g/mol), assumed to not be significantly affected by the steric hindrance, thus providing faster transport than large molecule contrast agents (e.g., ioxaglate). Cylindrical samples (d = 6 mm, h = 2 mm) were prepared from healthy bovine (n = 10) patella and meniscus, immersed in isotonic phosphate-buffered NaI solution (20 mgI/mL), and subsequently imaged with a micro-CT at 20 time points up to 23 h. Subsequently, normalized attenuation and contrast agent flux, as well as water, collagen, and proteoglycan (PG) contents in the tissues were determined. Normalized attenuation at equilibrium was higher (p = 0.005) in meniscus. Contrast agent flux was lower (p = 0.005) in the meniscus at 10 min, but higher (p < 0.05) between 30 and 120 min. In both tissues, contrast agent distribution at equilibrium suggested an inverse agreement with the depth-wise PG distribution. In conclusion, iodine transport into cartilage and meniscus was different, especially between the first 2 hours after the immersion. This is an important finding which should be considered during simultaneous CECT of cartilage and meniscus.

Relationships between tissue composition and viscoelastic properties in human trabecular bone.

Trabecular bone is a metabolically active tissue with a high surface to volume ratio. It exhibits viscoelastic properties that may change during aging. Changes in bone properties due to altered metabolism are sensitively revealed in trabecular bone. However, the relationships between material composition and viscoelastic properties of bone, and their changes during aging have not yet been elucidated. In this study, trabecular bone samples from the femoral neck of male cadavers (n=21) aged 17-82 years were collected and the tissue level composition and its associations with the tissue viscoelastic properties were evaluated by using Raman microspectroscopy and nanoindentation, respectively. For composition, collagen content, mineralization, carbonate substitution and mineral crystallinity were evaluated. The calculated mechanical properties included reduced modulus (Er), hardness (H) and the creep parameters (E1, E2, η1and η2), as obtained by fitting the experimental data to the Burgers model. The results indicated that the creep parameters, E1, E2, η1and η2, were linearly correlated with mineral crystallinity (r=0.769-0.924, p<0.001). Creep time constant (η2/E2) tended to increase with crystallinity (r=0.422, p=0.057). With age, the mineralization decreased (r=-0.587, p=0.005) while the carbonate substitution increased (r=0.728, p<0.001). Age showed no significant associations with nanoindentation parameters. The present findings suggest that, at the tissue-level, the viscoelastic properties of trabecular bone are related to the changes in characteristics of bone mineral. This association may be independent of human age.

Hyperosmolaric contrast agents in cartilage tomography may expose cartilage to overload-induced cell death.

In clinical arthrographic examination, strong hypertonic contrast agents are injected directly into the joint space. This may reduce the stiffness of articular cartilage, which is further hypothesized to lead to overload-induced cell death. We investigated the cell death in articular cartilage while the tissue was compressed in situ in physiological saline solution and in full strength hypertonic X-ray contrast agent Hexabrix(TM). Samples were prepared from bovine patellae and stored in Dulbecco's Modified Eagle's Medium overnight. Further, impact tests with or without creep were conducted for the samples with contact stresses and creep times changing from 1 MPa to 10 MPa and from 0 min to 15 min, respectively. Finally, depth-dependent cell viability was assessed with a confocal microscope. In order to characterize changes in the biomechanical properties of cartilage as a result of the use of Hexabrix™, stress-relaxation tests were conducted for the samples immersed in Hexabrix™ and phosphate buffered saline (PBS). Both dynamic and equilibrium modulus of the samples immersed in Hexabrix™ were significantly (p<0.05) lower than those of the samples immersed in PBS. Cartilage samples immersed in physiological saline solution showed load-induced cell death primarily in the superficial and middle zones. However, under high 8-10 MPa contact stresses, the samples immersed in full strength Hexabrix™ showed significantly (p<0.05) higher number of dead cells than the samples compressed in physiological saline, especially in the deep zone of cartilage. In conclusion, excessive loading stresses followed by tissue creep might increase the risk for chondrocyte death in articular cartilage when immersed in hypertonic X-ray contrast agent, especially in the deep zone of cartilage.

Growth of human colorectal carcinoma implants in the mouse subrenal capsule assay.

The subrenal capsule assay (SRCA) in normal immunocompetent mice was performed from 1331 implants of 43 human colorectal carcinomas to evaluate the possible applications for clinical chemosensitivity testing. Also the effect of an immunosuppressive agent, cyclosporine, was tested on the growth of tumours. Histologically in all except one of 23 saline-treated tumours the original tumour tissue was replaced by granulation tissue and inflammatory cells. This was also true in cyclosporine-treated mice since in only one of the nine tests tumour cells were observed. The macroscopic growth of the implants in the cyclosporine-treated mice was significantly less than in the saline-treated mice. Flow cytometric DNA-analysis revealed that the difference between macroscopic growth of saline and cyclosporine-treated groups was observed only in DNA-diploid tumours. We conclude that new methods are required to preserve the viability of human colorectal carcinoma in the SRCA.

Fecal free and conjugated bile acids and neutral sterols in vegetarians, omnivores, and patients with colorectal cancer.

Increased excretion and intestinal bacterial metabolism of bile acids and neutral sterols have been suggested to be associated with an increased risk of colorectal cancer. We determined fecal neutral sterol and bile acid profiles by new capillary column gas-liquid chromatographic methods in 18 patients with colorectal cancer, 10 omnivores, and 10 vegetarians. The methods also determine concentrations of esterified neutral sterols and saponifiable bile acids formed by intestinal bacterial action. Patients with colorectal cancer had the highest concentrations of neutral animal sterols, the lowest degree of esterification of neutral sterols, the lowest relative amount of saponifiable bile acids, and the highest concentrations of unconjugated primary bile acids. These differences were statistically significant (p less than 0.05) and more profound when the patients were compared with vegetarians than with omnivores. Since epidemiologic studies suggest that vegetarians have a lower risk of colorectal cancer than omnivores, these differences are discussed as possible risk factors for colorectal cancer.

Results of 32 major hepatic resections for primary and secondary malignancies of the liver.

Thirty-two consecutive liver resections performed during the years 1972-1984 for liver malignancies have been analysed. Among indications for resection were primary liver malignancy and liver secondaries equally often in 16 patients, mostly originating from colorectal cancer (12 patients). Ultrasound (US) was the most reliable diagnostic method being fully confident in 11 patients studied. Computed tomography (CT) missed one lesion out of 13 (confidence rate 92%), whereas angiography and liver scintiscan missed two and three lesions respectively with a confidence rate of 84 and 79. Most of the patients (94%) experienced an anatomical liver resection including 12 extended right lobectomies (ERL), eight right lobectomies (RL), five left lobectomies (LL), and five left lateral segmentectomies (LLS). The hospital mortality (16%) was almost exclusively connected to the ERL procedure with a 33% mortality rate. The crude 3-year survival rate of the series was 28%. Among the patients undergoing liver resection for colorectal cancer secondaries the corresponding figure was 41%. More than half of the patients surviving surgery have died of the same malignancy mostly developing in the remaining liver.

Cancer in ulcerative colitis: what failed in follow-up?

In a 16-year series of 235 patients operated on for ulcerative colitis (UC), 16 patients had altogether 21 colorectal malignancies: 15 patients adenocarcinomas and 1 a lymphoma. These patients were analyzed to find the typical features of colitic cancer and to evaluate the chance for early detection of cancer. The mean age of the patients was 35 years (19-86), and the mean duration of UC 14 years (5-26). All patients had total colitis, and 13 of 21 tumours (62%) were located proximal to the splenic flexure. Three patients under regular surveillance had Dukes' stage A cancers, while those with only initial or no follow-up had more advanced tumours (1 Dukes' A, B, 1C, 10D). Early cancer was symptomless or indistinguishable from colitic symptoms. The reasons for inadequate surveillance were few symptoms of UC (n = 9), an unsatisfactory follow-up system (n = 3) and patient refusal (n = 1). Our survey indicates that only regular follow-up can disclose early tumours and, thus, improve the prognosis of colitic carcinoma. The necessity of establishing colonoscopic surveillance of UC patients soon after the diagnosis, and regardless of the degree of symptoms is emphasized, because 7 (44%) of our patients developed cancer within 10 years of the onset of UC.

Five guaiac-based tests for occult blood in faeces compared in vitro and in vivo.

Five guaiac-based faecal occult blood tests (Fecatest, Fecatwin Sensitive, Fecatwin, Haemoccult, Hemafecia) were compared in vitro and in vivo and the effect of time between sample application and development of the colour reaction was studied. In both type of experiments the sensitivity of Fecatest, Fecatwin Sensitive and Fecatwin was higher when the colour reaction was developed at 24-72 h than at 2 h after application of the sample but for Haemoccult and Hemafecia the sensitivity in in vivo experiments was constant or tended to decrease with time. In upper gastrointestinal bleeding false negative test results were obtained for Fecatest, Fecatwin Sensitive, Fecatwin, Haemoccult and Hemafecia in 21, 23, 38, 43 and 43%, respectively. In colorectal bleeding the corresponding percentages were 10, 10, 35, 35 and 35. Using the 51Cr-erythrocyte method, quantitative estimation of intestinal bleeding was performed in 20 patients with verified colorectal cancer and in 11 control patients. When the patient was bleeding from left hemicolon 29% of the Fecatwin, Haemoccult and Hemafecia test results were negative, 10% were negative for Fecatest and 14% for Fecatwin Sensitive. In patients with tumours in right hemicolon Fecatest and Fecatwin Sensitive were positive in all samples, whereas the other tests were negative in 10%. Experiments revealed that the proportion of false positives due to dietary factors correlated with the sensitivity of the tests.

Colorectal carcinoma before 40 years of age: prognosis and predisposing conditions.

The prognosis and the occurrence of premalignant conditions were studied in 249 patients with colorectal carcinoma, diagnosed before the age of 40 years, between 1970 and 1979, in Finland. The aim was to evaluate the possibilities for prevention and screening of colorectal carcinoma in young people. The 5-year survival (41%) corresponded to that observed generally in colorectal carcinoma. The therapeutic delay (mean, 8.6 months) was not longer in the advanced stages (Duke's C, D), which comprised 53% of all, than in the localized stages. A premalignant condition occurred in 46 patients (18.5%): familial adenomatous polyposis coli in 18 (7.2%), ulcerous colitis in 11 (4.4%), cancer family syndrome in 9 (3.6%), and miscellaneous conditions in 8 (3.2%) patients. The younger the patient, the more often a premalignant condition was found. Nearly half of the high-risk patients could have been identified earlier. The findings suggest that more emphasis should be placed on the identification, family screening, and treatment of the conditions predisposing to colorectal cancer.

Immunological detection of faecal occult blood in colorectal cancer.

A new two-phase test kit for faecal occult blood combining a sensitive guaiac test (Fecatwin (S)ensitive) with an immunological test for human haemoglobin (FECA-EIA) was compared with three current guaiac tests (Fecatest, Fecatwin, Haemoccult) in 19 colorectal cancer patients and 11 controls on a restricted diet. A total of 43 48 h faecal samples (30 from cancer patients and 13 from controls) were collected for quantitative determination of faecal blood loss with the 51Cr method. Qualitative testing revealed that FECA-EIA was the most sensitive test, giving one (3%) false negative test result in the 30 tests on colorectal cancer patients and no false positives in the control subjects. It was also the only test that detected low-degree tumour bleeding. Fecatest and Fecatwin S were the most sensitive guaiac tests, giving 7 and 10% false negative test results, respectively, in the 30 colorectal cancer samples, whereas Haemoccult and Fecatwin gave 23% false negative test results. For screening purposes and in order to reduce costs it is suggested that only the positive test results of the very sensitive guaiac test (Fecatwin S) should be tested with the FECA-EIA test to eliminate false positive results. With this approach the diagnostic accuracy of the new two-phase test will be about twice as good as for the Haemoccult test.

Surgical results in 657 patients with colorectal cancer.

Six hundred fifty-seven patients with colorectal cancer who were operated upon at the Second Department of Surgery, Helsinki University Central Hospital during the period 1966 to 1975 had a 40.5 per cent crude five-year survival rate and 54.2 per cent relative (corrected) rate. The survival rates of patients with Dukes' A lesions were 80.7 per cent, Dukes' B, 61.6 per cent, Dukes' C, 40.4 per cent, and Dukes' D, 2.7 per cent. One hundred two patients (15.5 per cent) underwent emergency operations; 91 were occlusive cancers, eight were perforations and three were cancer bleedings. The operative mortality for the whole series was 6.5 per cent (4.7 per cent in elective and 16.7 per cent in emergency operations). A definite improvement of the five-year survival rates could be seen in both the colonic and rectal cancer series. This was due to earlier detection of the disease, reflecting a decreasing number of palliative operations. Patients at high risk for colorectal cancer (inflammatory bowel disease, inherited intestinal polyposis, cancer family syndrome, multiple colorectal cancers, and neoplastic polyps) might benefit from more effective cancer surveillance and prophylactic surgery to find and treat cancers in earlier stages, to prevent recurrences, and to facilitate follow-up. The controversial findings on postoperative adjuvant therapy presented in this study indicate the need for further controlled studies to define the patients who really benefit from it.

Colorectal cancer obstruction: a challenge to improve prognosis.

Probable factors contributing to the prognosis in 91 colorectal cancer obstructions operated on as emergencies were compared with 555 nonobstructive patients undergoing elective surgery in the same period, 1966-1975. The obstructive patients were older than the elective ones, with a statistically significant difference in the age range 80 years and older. Obstructive lesions were mainly located in the left hemicolon (56%). Although the sigmoid was the most frequent site, only lesions at the splenic flexure occurred more frequently than in patients without obstruction. Lesions in the right hemicolon were predominant in obstructive patients younger than 50 years. The overall 5-year survival for patients with obstructions was 21% but only 8% in those younger than 50 years. The corresponding figures for elective patients were 44% and 53%, respectively. The poorer overall prognosis in the obstruction group was mainly due to a higher postoperative mortality (15.4% vs. 4.7%) and a higher incidence of advanced cancer (stage C + D; 67% vs. 50%). Advanced disease was especially predominant in patients below the age of 50 years. However, this group had no operative mortality. A one-stage operation was performed only for obstructive lesions in the right hemicolon where it was the main (54%) procedure. Obstruction due to cancer in the left hemicolon were managed by Hartmann's procedure and a staged operation with almost equal frequency in 80% of the patients. Crude survival figures favour the staged operation. Obstructive lesions in the left hemicolon had a considerably better 5-year survival than those in the right hemicolon (29% vs. 15%), whereas none of those with rectal obstruction survived for 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Delay in the diagnosis of colorectal cancer.

The causes of long delay by the doctor (Dd) in the diagnosis of colorectal cancer are discussed. The median delay in this whole prospective material (100 patients) was 9.8 months (Dd 5.4 months and patient's delay (Pd) 4.4 months) compared to 18.1 months (Dd 14.7 months and Pd 3.4 months) in the 30 patients severely delayed (Dd more than 6 months). A false negative barium enema (16 patients) and acceptance of the patient's symptoms without resort to investigation were the main causes of severe delay. The most common error of diagnosis were haemorrhoids and anaemia. Tumours in the right hemicolon were the most difficult one to diagnose representing 53% of those severely delayed. The false negative barium enemas were mainly attributed to small sized early stage cancers of which 69% were located in right hemicolon, indicating also the diagnostic difficulties in this part of the colon. The age distribution among those severely delayed showed slight predominance of patients younger than 50 years, resulting from lack of cancer-conscious attitude of the doctors examining younger patients. Males outnumbered females among those severely delayed. This study emphasizes that a more cancer-conscious doctor with a more critical attitude to barium enema examination and willing to use colorectal endoscopy in the diagnosis of colorectal diseases provides the key to a shorter delay and thus maybe to improved survival

Increased risk of colorectal cancer after cholecystectomy.

The relative risk of developing colorectal cancer after cholecystectomy has been assessed in a retrospective autopsy study using controls individually matched for age and sex. Of the 304 patients dying with colorectal cancer and undergoing autopsy examination at the Helsinki University Central Hospital, 45 had undergone previous cholecystectomy. The corresponding number for the matched-pair controls without colorectal cancer was 32, indicating that the relative risk of developing colorectal cancer is slightly (1.59), but significantly (p less than 0.05), increased after cholecystectomy. The relative risk was highest for cancer of the right colon (3.00). In contrast, no difference in the autopsy incidence of unoperated gallstones was observed between the two groups, suggesting that, rather than lithogenic bile alone, the predisposing factor is related to the cholecystectomy procedure itself.

Bleeding oesophageal varices caused by the Budd-Chiari syndrome treated by the Warren shunt.

A previously healthy nonalcoholic 21-year old man was admitted to the hospital for further investigation because of previous severe haematemesis. Oesophageal varices proved to be the origin of the bleeding. The underlying cause for portal hypertension was total obstruction of the left and 70% obstruction of the right hepatic veins (chronic Budd-Chiari syndrome). Portal flow to the liver was almost normal due to well developed collaterals to the azygos vein and the patient's liver function was good. Distal splenorenal shunt (Warren shunt) was performed to decompress the varices. Postoperative recovery was uneventful and 10 months later the patient's general condition was excellent. Varices had disappeared and there was also improvement in his haematological status.