[Changed diagnosis and treatment in hepatocellular carcinoma].
Explore the source record for details and available documents.
Carcinoma, Hepatocellular↗
Biomedical subjects
T Wobbes
Publications and source records attributed to T Wobbes.
Comparative MO-QSAR studies in various species including man.
In the present study it is demonstrated that MO-QSARs (quantitative structure activity relationships based on calculated molecular orbital substrate characteristics) of cytochrome P450-catalysed biotransformation of benzene derivatives obtained in previous studies for Wistar rats, can be extrapolated to other species, including man. First, it was demonstrated that the regioselectivity of the in vivo aromatic hydroxylation of two fluorobenzene derivatives can be quantitatively predicted, on the basis of the calculated density distribution of the reactive pi-electrons in the aromatic ring of the fluorobenzene derivative, for all experimental animal species tested. Second, it was investigated whether the preferential site for in vitro aromatic hydroxylation of 3-fluoroaniline could be predicted on the basis of the same calculated parameter. This was done because extrapolation to human systems requires in vitro instead of in vivo experiments. The results obtained indicated that the variation in the regioselectivity of the aromatic hydroxylation of 3-fluoroaniline by liver microsomes from different species, including man, was only a few percent, and was mainly directed by calculated chemical reactivity characteristics of the 3-fluoraniline substrate. Finally, possibilities for the extrapolation from rat to other species, of the MO-QSAR for the rate of in vitro C4 hydroxylation of a series of aniline derivatives converted in an iodosobenzene-supported microsomal cytochrome P450 system, were investigated. Experiments with liver microsomes from rats, mice, rabbit and man resulted in clear MO-QSARs with correlation coefficients for the relationship between the 1n k(cat) and the E(HOMO) of the aniline substrates that were > or = to 0.97 in all cases. Thus, the results of the present study clearly demonstrate that MO-QSARs previously described for Wistar rats can be extrapolated to mice, rabbit, guinea pig and even to man. Regioselectivities obtained and QSAR lines for the rate of conversion plotted against calculated E(HOMO) values of the aniline derivatives are similar for the various species investigated. Altogether, these results strongly support the conclusion that the conversion of the relatively small benzene derivatives in the relatively large and aspecific active sites of the mammalian cytochromes P450, even when derived from various species, are mainly dependent on chemical reactivity parameters of the substrates. Therefore, the results of the present study support the hypothesis that MO-based QSARs obtained in rat for the cytochrome P450 catalysed aromatic hydroxylation of benzene derivatives can provide a basis for prediction of biotransformation pathways in different species, including man.
Aged↗
Combined preoperative irradiation and local hyperthermia delays early healing of experimental colonic anastomoses.
OBJECTIVE: To determine if a combination of preoperative irradiation and local hyperthermia of a colonic segment is detrimental to subsequent early anastomotic healing. DESIGN: A prospective randomized experimental trial. SETTING: An animal research laboratory. INTERVENTIONS: Eighty male Wistar rats were randomly divided into 4 groups. In each animal, a segment of the colon was treated successively by (sham) irradiation and (sham) hyperthermia. After 5 days, a colonic resection was performed and an anastomosis was constructed; the distal limb consisted of (sham) irradiated, (sham) hyperthermia-treated bowel. The rats were killed 3 or 7 days after surgery. MAIN OUTCOME MEASURES: Body weight, serum albumin and protein levels, anastomotic bursting pressure, breaking strength, and hydroxyproline content. RESULTS: All animals tolerated (sham) treatment well. Weight was diminished, though not notably, in treated animals vs the control group. After combined preoperative irradiation and hyperthermia, the frequency of local anastomotic complications increased: 4 of 20 animals had a covered perforation when they were killed. In this group, the bursting pressure was lower 3 days after the operation (P = .008). The breaking strength was also lower but not notably. The serum albumin level was significantly lower in this group vs the control group (P = .006); the serum protein level was not decreased. After 7 days, no differences existed between the groups. The hydroxyproline content of the anastomotic tissue was notably higher in rats treated with radiation plus hyperthermia vs control rats (in both the 3- and 7-day groups). The anastomotic hydroxyproline concentration did not differ between the groups. CONCLUSIONS: The combination of preoperative irradiation and hyperthermia results in increased local anastomotic complications. Anastomotic strength is at risk in the first days after the anastomotic reconstruction. Preoperative irradiation or hyperthermia alone does not lead to impaired anastomotic healing in the early phase.
Anastomosis, Surgical↗
Interval carcinomas of the breast: a group with intermediate outcome.
BACKGROUND: Interval carcinoma is defined as a carcinoma detected between two mammographic screening rounds after a negative screening. By some authors these carcinomas are considered to be more aggressive than screen-detected carcinomas. METHODS: In a group of 937 patients referred for breast cancer in the period 1975-1990, 76 interval carcinoma patients were treated. In a retrospective study the outcome was studied of patients with an interval carcinoma in comparison with patients with screen-detected carcinomas and of patients with clinically detected carcinomas outside the screening program. RESULTS: No significant difference was found in the 5-year and 10-year disease-free survival of patients with interval carcinoma (80%, 68%) and the screen-detected group (89%, 81%) (P = 0.12). The interval group did significantly better than the patients with carcinomas detected outside the screening program (P = 0.03). CONCLUSION: Interval-detected cancers for patients in the screening program had an outcome intermediate between patients with screen-detected cancers and patients with cancers detected outside the screening program. The difference between interval-detected cancers and cancers detected outside the screening program was significant, whereas the difference between screen-detected and interval cancers was not.
Actuarial Analysis↗
Combined preoperative irradiation and direct postoperative 5-fluorouracil without negative effects on early anastomotic healing in the rat colon.
BACKGROUND AND PURPOSE: Preoperative irradiation with direct postoperative chemotherapy could benefit patients undergoing surgery for colorectal cancer. This study was designed to examine, in an experimental model, if such treatment is feasible without detrimental effects on early anastomotic healing. MATERIAL AND METHODS: A colonic segment was irradiated (25 Gy) in 3 groups (n = 10 each) of male Wistar rats. After 5 days, a colonic resection was performed with anastomotic construction; only the distal limb consisted of irradiated bowel. Postoperatively, animals received daily intraperitoneal 5-fluorouracil (5-FU, group I/CH: 17.5 mg/kg; group I/CL: 12.5 mg/kg) or saline (group I). Three additional groups were treated similarly, but with sham-irradiation: CH, CL and C, respectively. All rats were killed 7 days postoperatively. Parameters measured were: weight, serum albumin and protein, and anastomotic bursting pressure, breaking strength and hydroxyproline content. RESULTS: Body weight was diminished significantly in rats receiving chemotherapy. Serum albumin and protein was significantly lower in irradiated groups. At sacrifice, 40% of I/CH rats had functional rectal stenosis. The average bursting pressure (P = 0.0005) and the average breaking strength (P = 0.012) were only reduced significantly in the CH group. The anastomotic hydroxyproline content was significantly higher in the I/CH and I/CL groups vs. the control group. CONCLUSION: High-dose direct postoperative 5-FU leads to reduced anastomotic strength. Although the combination of preoperative irradiation (25 Gy) and direct postoperative high-dose 5-FU does not reduce early anastomotic strength, some stenosis may occur. The combination of preoperative irradiation and low-dose 5-FU has no such effect.
Anastomosis, Surgical↗
The effects of 5-fluorouracil and interferon-alpha on early healing of experimental intestinal anastomoses.
The continuing search for effective adjuvant therapy after resection of intestinal malignancies has prompted a growing interest in both immediate post-operative regional chemotherapy and the combination of 5-fluorouracil (5-FU) and interferon-alpha as drugs of choice. We have compared the effects of both compounds, alone and together, on early healing of intestinal anastomoses. Four groups (n = 26 each) of rats underwent resection and anastomosis of both ileum and colon: a control group and three groups receiving intraperitoneal 5-FU, interferon-alpha or both on the day of surgery and the next 2 days. Animals were killed 3 or 7 days (n = 10 each) after operation in order to measure anastomotic strength and hydroxyproline content. The remaining six animals in each group were used to study anastomotic collagen synthetic capacity at day 3. Three days after operation, ileal anastomotic bursting pressure was lowered by 37% in the 5-FU/interferon-alpha group (P = 0.0104). At day 7, anastomotic breaking strength was reduced significantly in ileum (P = 0.0221) and colon (P = 0.0054) of the 5-FU/interferon-alpha group and in colon of the interferon-alpha group (P = 0.0221). Collagen synthetic capacity was strongly suppressed by 5-FU but not by interferon-alpha. However, no differences in anastomotic hydroxyproline content were observed between groups at both days 3 and 7. Thus, post-operative use of interferon-alpha, in particular in combination with 5-FU, may be detrimental to anastomotic repair in the intestine.
Anastomosis, Surgical↗
Divergent patterns of matrix metalloproteinase activity during wound healing in ileum and colon of rats.
BACKGROUND: Uncontrolled and increased extracellular matrix degradation during early anastomotic repair in the intestine may reduce wound strength increasing the risk of anastomotic dehiscence. AIMS: To characterise the metalloproteinases present in intact and anastomosed ileum and colon to study their role in matrix degradation after surgery. SUBJECTS: Tissue extracts of uninjured, and of anastomosed rat ileum and colon at postoperative days 1, 2, 3, 7, and 90, were used. METHODS: Metalloproteinases were identified by gelatin and casein zymography. Aminophenylmercuric acetate (APMA) treatment was used to activate latent metalloproteinases. RESULTS: Both uninjured ileum and colon contained a 60 and 67 kDa activity, but a 54 and 72 kDa gelatinase was present in ileum only, and a 51 kDa activity in colon only. APMA treatment converted the 60 kDa protease to 54 and 51 kDa forms and the 72 kDa protease to the 67 kDa form. These gelatinases may correspond to latent and active forms of MMP 1 and MMP 2, respectively. Additional metalloproteinases were observed after anastomotic construction. Both ileum and colon contained 95 and 230 kDa gelatinases, which were converted to 83 and 76 kDa forms by APMA. They may be the latent and active forms of MMP 9, respectively. Gelatinolytic activities of 25 and 28 kDa were only found in anastomosed ileum. Caseinolytic activities were only found in ileum extracts and those were most prominent at day 1, 2, and 3 after surgery. CONCLUSIONS: The metalloproteinase pattern in ileum and colon differ considerably suggesting that matrix degradation after anastomotic construction may also vary.
Animals↗
Effect of a breast saving procedure on lactation.
Explore the source record for details and available documents.
Adult↗
[Anal blood loss in pregnancy, a symptom which should be taken seriously].
Explore the source record for details and available documents.
Adenocarcinoma↗
Retinol may promote fluorouracil-suppressed healing of experimental intestinal anastomoses.
OBJECTIVES: To examine the effects of perioperative administration of fluorouracil on healing variables of internal anastomoses and to explore ways to promote repair under these conditions. DESIGN: Seven-day, prospective randomized experimental trial. SETTING: Animal research laboratory. ANIMALS: Male young-adult Wistar rats after resection and anastomosis of both ileum and colon. INTERVENTIONS: Random assignment to groups receiving placebo, daily fluorouracil (20 mg/kg per day, intraperitoneally), daily fluorouracil plus retinol palmitate (5000 IU/kg per day, orally), daily fluorouracil plus interleukin-2 (2 x 10(6) IU/kg per day, subcutaneously), or daily fluorouracil plus granulocyte macrophage colony-stimulating factor on the first 4 days after operation (20 micrograms/kg per day, intraperitoneally. MAIN OUTCOME MEASURES: Anastomotic bursting pressure, breaking strength, hydroxyproline content, and ex vivo collagen synthetic capacity. RESULTS: Administration of fluorouracil decreased anastomotic breaking strength by more than 40% and caused a shift in bursting site from outside to within the suture line. It also lowered anastomotic hydroxyproline content. The capacity for collagen synthesis, which was greatly enhanced in 4-day-old anastomoses from the control group, was significantly (P < .05) and specifically reduced. Concomitant administration of retinol resulted in restoration of strength and hydroxyproline content, particularly in the ileum. Interleukin-2 and granulocyte macrophage colony-stimulating factor did not improve fluorouracil-suppressed repair: both wound strength and collagen content were similar in the fluorouracil, fluorouracil/interleukin-2, and fluorouracil/granulocyte macrophage colony-stimulating factor groups. CONCLUSION: Intraperitoneal administration of fluorouracil, delivered from the day of operation onward, severely reduces anastomotic strength at the end of the first postoperative week. This negative effect may be prevented by oral administration of retinol.
Anastomosis, Surgical↗
Radical resection of locally advanced colorectal cancer.
Multivisceral resection has been accepted as treatment for patients with locally advanced colorectal cancer. Nodal status has recently been claimed to be the most important predictor of survival in patients with such disease, with no survival after 2 years for patients with lymph node metastasis. A retrospective analysis was carried out of the prognostic significance of different tumour characteristics, and whether a more limited palliative resection is warranted in patients with positive lymph nodes. Of 1346 patients with colorectal adenocarcinoma operated on between 1987 and 1991, all those with a tumour staged as T4N0M0 or T4N1M0 (94 patients) were selected. From the remainder, 195 patients with stage T3N0M0 and T3N1M0 lesions were randomly selected as a control group. Overall survival was assessed at the beginning of 1993. The most important predictors of survival were lymph node status and involvement of the resection margins of the tumour. Overall survival in patients with T4 tumours who underwent radical resection was not significantly different from that in those with T3 tumours, even in N1 stages. Extended resection did not induce unacceptable morbidity or mortality. Surgery for locally advanced colorectal adenocarcinoma should result in tumour-free margins, and should therefore include multivisceral resection, even in patients with lymph node metastasis.
Adenocarcinoma↗
Ewing's sarcoma of bone: oncologic and functional results.
This paper describes 29 patients with Ewing's sarcoma of bone treated between 1975 and 1990 at the University of Nijmegen Hospital, Nijmegen, The Netherlands. Osteomyelitis was the primary diagnosis in 24%. Treatment consisted of chemotherapy in combination with surgery and/or radiotherapy. Nine patients received radiotherapy only; five of them died of disease. Five patients underwent an intralesional excision; four of them died of disease. Twelve patients underwent a wide excision; there is no evidence of disease in any of them. Three patients underwent a radical disarticulation; all died of disease. The disease-free survival at 1.5 years was 66%. This figure at 5 years was 55%. After wide excision and reconstruction in tumors of expendable, femoral or radial bones good functional results were obtained in all cases.
Adolescent↗
Intraoperative irradiation delays anastomotic repair in rat colon.
BACKGROUND: There exists a growing interest in intraoperative radiation therapy as a treatment modality for large-bowel cancer. Since such therapy could interfere with wound repair, we investigated its effects on early healing of colonic anastomoses. METHODS: After resection of 1 cm of colon, rats were irradiated with a single dose of 25 Gy, either to the proximal limb (P group) or to both proximal and distal limbs of the bowel (PD group) before anastomotic construction. Both groups were compared with a sham-irradiated control group. Animals were killed 3, 7, or 14 days after operation, and healing was assessed by mechanical and biochemical (collagen) parameters. RESULTS: Three days after operation, bursting pressure was significantly lowered in the P group, whereas in the PD group both bursting pressure and breaking strength were strongly reduced. At day 7, the breaking strength was still reduced in the PD group, but not significantly so in the P group. The collagen synthetic capacity of the anastomotic segments was significantly lowered in both irradiated groups at day 3, resulting in a diminished collagen concentration in the actual wound area after 7 days. At 14 days after operation, no differences in strength were found between control and irradiated groups, while anastomotic hydroxyproline levels were significantly higher in both the P and PD groups than in the control group. CONCLUSIONS: High-dose intraoperative radiation therapy delays the healing of colonic anastomoses; it transiently reduces strength, probably as a result of a diminished accumulation of collagen.
Anastomosis, Surgical↗
Post-operative levamisole may compromise early healing of experimental intestinal anastomoses.
There exists growing interest in immediate post-operative local adjuvant therapy after resection of intestinal malignancies. It is therefore necessary to assess it potential effect on the healing of intestinal anastomoses. Five groups (n = 20) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving intraperitoneal 5-fluorouracil (5-FU), 5-FU plus leucovorin, 5-FU plus levamisole or levamisole alone, on the day of surgery and the next 2 days. Animals were killed 3 or 7 days after operation. Another three groups (n = 6) of animals were used to compare anastomotic collagen synthetic capacity in control rats or rats receiving 5-FU or 5-FU plus levamisole. On the third post-operative day, the average anastomotic bursting pressure in the 5-FU/levamisole group was reduced by 36% as compared with the control group, both in ileum (P = 0.02) and in colon (P = 0.01). Values in the other groups were similar to those in the control group. Anastomotic breaking strength was significantly (P < 0.025) lowered in the ileum from the levamisole group at both days 3 and 7. Anastomotic collagen synthetic capacity was strongly reduced in the 5-FU and 5-FU/levamisole groups. However, there was no significant difference between the control group and the four experimental groups with regard to anastomotic hydroxyproline concentration and content, either 3 or 7 days after operation. Thus, limited use of levamisole, alone or in combination with intraperitoneal 5-FU, may compromise intestinal healing.
Anastomosis, Surgical↗
Breast tumors: comparative accuracy of MR imaging relative to mammography and US for demonstrating extent.
PURPOSE: To evaluate the comparative accuracy of magnetic resonance (MR) imaging relative to mammography and ultrasonography (US) for assessing the extent of breast tumors. MATERIALS AND METHODS: Histologic results and preoperative imaging findings (mammography, US, MR imaging) were analyzed regarding tumor size and multifocality of 61 tumors in 60 women undergoing mastectomy for carcinoma. RESULTS: In 10% of cases, the index tumor was not seen at mammography. With US, 15% of the index tumors were not recognized, while MR imaging missed 2% of the index tumors. On mammographic and US images, tumor size was underestimated significantly (P < .005), by 14% and 18%, respectively, while MR imaging showed no significant difference in size compared with that found in a pathologic evaluation. Mammography showed 31% of the additional invasive lesions, while US showed 38% and MR imaging showed 100%. CONCLUSION: MR imaging was the most accurate of the three preoperative imaging modalities in assessing the size and number of malignant lesions in the breast.
Adult↗
Analytical and clinical performance of improved Abbott IMx CA 125 assay: comparison with Abbott CA 125 RIA.
We compared the improved Abbott IMx cancer antigen (CA) 125 assay (cat. no. 7A89) with the Abbott CA 125 RIA. Serum specimens were from healthy perimenopausal women (n = 124) and from patients with benign gynecologic and nongynecologic diseases (n = 124), ovarian carcinoma (n = 104), or other malignancies (n = 193). The IMx assay detected as little as 0.193 kAU/L CA 125 (AU = arbitrary Abbott unit), demonstrated up to 29% overestimation upon serum dilution, low within-assay (2.7-5.6%) and between-assay (4.8-8.2%) CVs, and no high-dose hook effect < or = 46,000 kAU/L nor influence from human anti-mouse antibodies in serum of women injected with OC 125 F(ab')2. Values by IMx were 20% lower than by RIA for healthy perimenopausal women (n = 100; IMx = 0.80 RIA - 2.5 kAU/L), and at least 50% higher for those with benign or malignant ovarian disorders at concentrations < 100 kAU/L. Receiver-operating characteristic (ROC) curve analysis of ovarian neoplasma vs perimenopausal controls indicated a gain of specificity and sensitivity with the improved IMx assay over the RIA, but ROC performance was the same with either assay if patients with benign ovarian disorders were used as controls.
Adolescent↗
Randomised controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted blood in surgery for colorectal cancer.
In retrospective studies, perioperative blood transfusions were associated with poor prognosis after surgery for cancer and were a major independent risk factor for postoperative bacterial infection. Leucocyte-depleted, in contrast to buffy-coat-depleted, blood has no immunosuppressive effects in transplantation and so might lack detrimental effects on cancer prognosis and postoperative infections. We studied this hypothesis in a controlled trial by randomly allocating patients to receive either leucocyte-depleted red cells or packed cells without buffy coat when blood was needed. Between 1987 and 1990, 871 eligible patients with colorectal cancer, including 697 patients operated upon with curative intent, were randomised in the 16 participating hospitals. Neither the eligible group nor the curative group showed significant differences between the two trial transfusions in survival, disease-free survival, cancer recurrence rates, or overall infection rates after an average follow-up of 36 months. Patients who had a curative resection and who received blood of any sort had a lower 3-year survival than non-transfused patients (69% vs 81%, p = 0.001) and a higher infection rate (39% vs 24%, p < 0.001). Colorectal cancer recurrence rates, however, were not influenced by blood transfusion (30% vs 26%, p = 0.22). These combined observations confirm the association between blood transfusion and poor patient survival but indicate that the relation is not due to promotion of cancer.
Adenocarcinoma↗
Chondrosarcoma of bone: oncologic and functional results.
A retrospective review of 27 patients (21 males and 6 females) with chondrosarcoma of bone was performed to evaluate the oncologic and functional results. The average age of the patients was 48 years (range: 17-76). The tumor sites were pelvis in 10 cases, distal femur in 2, proximal tibia in 3, rib in 2, and other in 10. One patient with Ollier's disease had chondrosarcoma at two different sites simultaneously. Surgical stages were I A in 8 cases, I B in 8, II A in 1, and II B in 10. Two patients had no surgical treatment. Amputation was performed in 5 cases and en bloc resection in 20. An uncontaminated radical or wide surgical margin was achieved in 13 of 25 cases. Additional surgery was performed in seven cases; for deep infection in one case and for local recurrence or metastasis in six. Local recurrence developed in seven patients (26%). At follow-up, four patients had died of disease (15%), one patient had died of another cause, and two patients were alive with disease (7%). No evidence of disease was found in 20 patients (74%). The oncologic results of limb salvage and amputation in chondrosarcoma of the limbs were good, although there was one failure of limb salvage, caused by infection. Due to surgical inaccessibility, results of the management of chondrosarcoma of the pelvis were poor. The average functional evaluation of 16 patients (average follow-up: 104 months) was 75% (range: 30-100). The Musculoskeletal Tumor Society ratings were excellent in four cases, good in seven, fair in four, and poor in one.
Adolescent↗