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T Wobbes

Publications and source records attributed to T Wobbes.

At least 91 records · Page 5Linked to original sources

Giant cell tumor of bone: oncologic and functional results.

Giant cell tumor of bone is a challenging surgical problem due to its mostly aggressive growth with tendency to recur locally, to develop in rare instances pulmonary metastases without histologic evidence of malignant changes, and due to its potential to dedifferentiate into a frankly malignant tumor in a limited number of patients. It is treated in many different ways because of the difficulties in finding a type of treatment with the best functional results without compromising oncologic results. This paper describes 19 patients with giant cell tumor of bone. Following 19 procedures (including 6 intracapsular resections [curettage]) in 17 patients in our hospital only 2 recurrences (10.5%) occurred, both after curettage. Functional results after curettage without recurrence were favorable. Marginal or wide resections did not result in any recurrence, but were functionally inferior to curettage; an exception to the latter was the resection-arthrodesis of the distal radius in one patient.

Adult↗

The phase of the menstrual cycle has no influence on the disease-free survival of patients with mammary carcinoma.

We evaluated the outcome of treatment for mammary carcinoma in 89 premenopausal women in relation to the phase of the menstrual cycle. The phase of the cycle was determined on the basis of serum concentrations of 17 beta-oestradiol and progesterone. The serum samples were collected 1 day prior to or on the day of operation. After a median follow-up of 4.1 years no significant differences in disease-free survival were found between the preovulatory (proliferative), periovulatory and post-ovulatory (luteal) groups. No differences in survival were found in these subgroups between the N0 and N1 subgroup. On the basis of this study we cannot confirm that the phase of the menstrual cycle during surgery has any effect on the eventual outcome in mammary carcinoma patients. However larger studies of this type are required before definitive conclusions can be reached.

Antineoplastic Combined Chemotherapy Protocols↗

Effect of irradiation on healing of newly made colonic anastomoses in the rat.

PURPOSE: Short-term effects of radiotherapy on the healing process of newly made colonic anastomoses are investigated by measuring the anastomotic strength in a rat model. METHODS AND MATERIALS: Four groups of Wistar rats were used. In all groups, rats underwent a 1 cm sigmoid resection with end-to-end anastomosis. Group I served as a control group. In group II the anastomosis was irradiated after closure of the abdominal wall with a single dose of 20 Gy of 250 kV x rays. Group III was irradiated with a single dose of 20 Gy while the abdominal wall was not closed, and the surrounding tissues were carefully covered by a lead plate, simulating intra-operative radiotherapy. Group IV was treated as group III, but a larger dose of 25 Gy was applied. Animals were sacrificed 3 or 7 days after the operation. General condition of the rats was determined by observation, weight loss, serum protein and albumin at sacrifice. Anastomotic healing was evaluated by inspection, bursting pressure, hydroxyproline and protein contents of the anastomotic segment. RESULTS: Direct postoperative externally irradiated rats (group II) showed a marked weight loss, hypoproteinaemia and hypo-albuminaemia because of involvement of small bowel in the irradiated volume. With respect to anastomotic healing there were no significant differences between control and irradiated groups. CONCLUSION: These data suggest that the application of a single dose of irradiation (20 and 25 Gy) on colonic anastomoses given in a direct postoperative or intraoperative model has no measurable side effect on the early healing of newly made colonic anastomoses. Direct postoperative external irradiation results in unwanted side effects in the adjacent bowel.

Anastomosis, Surgical↗

Early post-operative 5-fluorouracil does not affect the healing of experimental intestinal anastomoses.

5-Fluorouracil (5-FU) remains the mainstay for systemic treatment of colorectal cancer. In view of the increasing interest in peri-operative administration of antineoplastic agents, we have investigated the effects of early postoperative 5-FU on the healing of intestinal anastomoses in the rat. Animals underwent resection and anastomosis of both ileum and colon and 5-FU (20 mg/kg body weight) was given, either intravenously or intraperitoneally, on the day of surgery and the two subsequent days. Healing was assessed three and seven days after operation. Administration of 5-FU led to a reduced white blood cell count. However, anastomotic strength was not significantly reduced at either time point and anastomotic hydroxyproline content was not significantly affected. We suggest that limited use of 5-FU during or immediately after operation does not necessarily affect early anastomotic healing in the intestine.

Anastomosis, Surgical↗

CA 125 serum levels in the early post-operative period do not reflect tumour reduction obtained by cytoreductive surgery.

In order to assess whether CA 125 serum levels reflect the outcome of cytoreductive surgery, CA 125 antigen levels were determined prior to and after debulking surgery in 50 ovarian cancer patients and compared to CA 125 serum levels before and after surgery in a control group of 140 patients undergoing laparotomy for various malignant or benign diseases. A significant CA 125 decrease in the first post-operative week was seen in 56% of ovarian cancer patients whereas 26% remained stable and 18% showed a significant increase after surgery. Although removal of tumour had been complete in all 14 stage I-II ovarian carcinomas, only 2 of these patients showed a subsequent significant CA 125 decrease after cytoreductive surgery, while 4 patients showed a significant increase. Such increases of CA 125 following surgery were also seen in uterine carcinomas (30%), in gastrointestinal carcinomas (75%) and in patients after laparotomy for benign gynaecological diseases (23%). CA 125 pre-treatment levels were significantly lower in patients with post-operative increases than in patients with stable or decreasing CA 125 patterns. Patients with stable CA 125 levels also had lower CA 125 pretreatment levels compared to patients with a post-operative CA 125 decrease. Post-operative increases were observed for at least 2 weeks after debulking in the case of ovarian cancer. Pre-operative levels of these patients were either within the normal range or moderately elevated. Serial measurements during surgery in partial debulking showed a rapid CA 125 decline within 24 h followed by increasing CA 125 values thereafter. Our data indicate that CA 125 serum levels in the direct post-operative period do not always reflect the outcome of cytoreductive surgery. There appears to be an effect on CA 125 levels caused by the abdominal surgical procedure itself. Consequently, CA 125 levels after abdominal surgery should be interpreted with caution.

Adult↗

Inhibition of basal and TGF beta-induced fibroblast collagen synthesis by antineoplastic agents. Implications for wound healing.

Antineoplastic drugs, given in the perioperative period, are thought to be a hazard to wound repair. Since fibroblast collagen synthesis is crucial to healing, we examined the effects of bleomycin, cisplatin and 5-fluorouracil on collagen synthesis in confluent cultures of fibroblasts from human colon and skin. The drugs were added in final concentrations between 0.1 and 50 microM. Bleomycin did not affect collagen synthesis in colon fibroblasts but inhibited synthesis in skin fibroblasts. Collagen synthesis in colon fibroblasts was strongly, and specifically, inhibited by cisplatin while synthesis in skin fibroblasts was affected only slightly. 5-Fluorouracil had no effect whatsoever on the collagen synthetic capacity in either colon or skin fibroblasts. If skin fibroblasts were cultured in the presence of transforming growth factor beta (TGF beta), the antineoplastic agents inhibited the TGF beta-stimulated collagen synthesis at far lower concentrations than those needed to suppress non-stimulated synthesis. This effect was not observed in fibroblasts from colon. The possible implications of these observations, as pertain to the use of perioperative chemotherapy, are discussed. Since 5-fluorouracil did not directly affect collagen synthesis in colon fibroblasts under any of the conditions tested it is suggested that the data support the contention that this drug is relatively harmless for intestinal healing.

Bleomycin↗

Glutathione S-transferases in esophageal cancer.

Glutathione content and glutathione S-transferase enzyme activity as well as isoenzyme composition were studied in normal gastric cardia, normal squamous esophageal epithelium and corresponding malignant tumor of 10 patients with esophageal cancer. Mean values of glutathione (38 +/- 6 versus 36 +/- 12 nmol/mg protein) and glutathione S-transferase activity (532 +/- 44 versus 532 +/- 108 nmol/min mg protein) did not differ significantly between normal esophageal and tumor tissue. However, great individual differences exist. In two patients, glutathione S-transferase activity was much higher in the tumor (1081 and 1381 nmol/min mg protein) due to overexpression of class alpha, mu and pig glutathione S-transferases in one case, and of class mu and pi in the other case. In the other patients, glutathione S-transferase activity was equal (one case) or lower (seven cases) in the tumor. In normal gastric cardia glutathione content as well as glutathione S-transferase activity was significantly lower as compared to normal esophageal epithelium. In conclusion, in contrast to other gastrointestinal tumors, glutathione S-transferases are overexpressed in esophageal tumors in only a limited number of patients.

Adult↗

Opposite effects of interleukin-2 on normal and transfusion-suppressed healing of experimental intestinal anastomoses.

OBJECTIVE: This study was done to investigate whether administration of interleukin-2 (IL-2) can abrogate the negative effects of blood transfusions on anastomotic healing. SUMMARY BACKGROUND DATA: Recently, the authors showed that blood transfusion severely impairs anastomotic repair and significantly increases the susceptibility to intra-abdominal septic complications in rats. It has been reported that blood transfusions suppress IL-2 production and that IL-2 may stimulate wound healing. METHODS: Lewis rats underwent resection and anastomosis of both the ileum and colon. Subsequently, they received either 3 mL of saline (control and IL-2 groups) or 3 mL of blood from brown Norway donors (transfusion and transfusion/IL-2 groups) intravenously. From the operation onward, the animals in the IL-2 and transfusion/IL-2 groups received daily injections of 5.4 x 10(5) IU of IL-2 in dextrose solution subcutaneously; the rats in the other groups received only the dextrose solution. The animals were killed 3 or 7 days after the operation and examined for septic complications and anastomotic repair. RESULTS: Transfusion led to an enhanced incidence of anastomotic abscesses, which was almost completely abrogated after IL-2 administration. The anastomotic strength was consistently and significantly reduced after transfusion. Seven days after surgery, the anastomotic strength was completely restored by IL-2 treatment. For instance, the average bursting pressure (+/- the standard deviation) of the ileal anastomoses in the control, transfusion, and transfusion/IL-2 groups were 86 +/- 15, 32 +/- 8,* and 63 +/- 10 mmHg* [symbol: see text] on day 3 and 293 +/- 36, 227 +/- 16,* and 299 +/- 19 mmHg on day 7, respectively (where * = significant vs. control group and [symbol: see text] = significant vs. transfusion group). In addition, IL-2 administration elevated the anastomotic hydroxyproline content, which was significantly decreased by transfusion alone, to the level found in the control group. The administration of IL-2 to control animals resulted unexpectedly in a significant reduction in anastomotic strength. CONCLUSIONS: Exogenous IL-2 reverses the negative effects of blood transfusions on anastomotic repair, but it impairs healing under normal conditions.

Abscess↗

Evaluation of colorectal cancer-associated mucin CA M43 assay in serum.

The technical performance of a newly developed assay for CA M43, a serum marker for colorectal cancer, was evaluated and its preliminary clinical potential assessed. The heterologous double-determinant enzyme immunoassay for the detection of the tumor-associated mucin CA M43 utilizes two monoclonal antibodies (CT 43 and CT 66) selected for their binding capacity to two distinct epitopes present on mucins in the sera of patients with colorectal cancer. CT 66 recognizes both Lewis(a) and sialylated Lewis(a) antigen; CT 43 is directed toward a mucin epitope of an as-yet uncharacterized structure. Precision experiments revealed interassay CVs of 11.8%, 5.9%, and 4.9% at 9.3, 11.9, and 78.9 units/mL, respectively; intraassay precision was 2.0% at 95.1 units/mL. The upper normal value was set at 7.5 units/mL, which included 99% of the values found in healthy controls. In colorectal cancer patients, CA M43 showed a positivity rate equivalent to that of carcinoembryonic antigen (CEA) and superior to that of CA 19.9, with only one CA 19.9-positive serum being negative for CA M43. Interestingly, CA M43 appeared to be complementary to CEA, with CA M43 and CEA together reaching 87% positivity in metastatic disease.

Adult↗

Evaluation of seven tumor markers (CA 50, CA 19-9, CA 19-9 TruQuant, CA 72-4, CA 195, carcinoembryonic antigen, and tissue polypeptide antigen) in the pretreatment sera of patients with gastric carcinoma.

Preoperative serum levels of the tumor markers CA 50, CA 19-9, CA 19-9 TruQuant, CA 72-4, CA 195, carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) were measured in 94 patients with well-staged adenocarcinoma of the stomach and in 15 patients with benign gastric diseases. In all patients with carcinoma, a laparotomy was done. The serum levels were correlated with the stage of disease, the location of the primary tumor, and the resectability and grade of differentiation. The marker CA 50 was the best, with an overall positivity of 59.5%. For CA 19-9, this figure was 34%; for CA 19-9 TruQuant, 22%; for CA 72-4, 34%; for CA 195, 29%; for CEA, 33%; and for TPA, 50%. The best combination of two markers was CA 50 and TPA; this combination gave a positivity of 81%. There was no evident correlation with stage of disease and the percentage of positive serum levels or the median serum levels. The marker CA 50 gave the widest range of elevated serum levels between the cutoff level and the 90th percentile (54%). Patients with carcinoma of the cardia had higher preoperative serum levels than those with a tumor in other parts of the stomach. There was no correlation with the resectability of the tumor and the preoperative serum level. Patients with an undifferentiated tumors did not have significantly lower serum levels than those with more differentiated tumors. Currently, preoperative determination of serum tumor marker levels in patients with gastric carcinoma has no significant in clinical practice.

Adult↗

Morphometric analysis of the effects of antineoplastic drugs on mucosa of normal ileum and ileal anastomoses in rats.

Antineoplastic agents affect the healing of intestinal anastomoses. They often induce anorexia and diarrhea, possibly caused by morphological changes in the small intestinal mucosa. These changes were evaluated in the rat ileum. Animals in group I underwent only intestinal surgery while those in groups II and III underwent surgery on the third day of a 5-day course with cisplatin (in two different doses), bleomycin, and 5-fluorouracil. The parameters were: number of mitoses in crypts, crypt depth, villus height, width, and contour length, measured in the mucosa of primarily resected segments of the ileum and of the anastomotic area. Surgery yields an increased crypt depth and villus length in the anastomotic area without changing villus width. The changes in intestinal crypts precede those in villi. Antineoplastic drugs decrease crypt mitotic rate, villus height, width, and contour length. After cessation of antineoplastic chemotherapy mitotic activity increases. The shallower and shorter villi increase in width and length resulting in an increased villus contour length and area. A linear relation exists between villus contour length and villus height and width. Thus, antineoplastic polychemotherapy, dose-dependently, reduces and surgical trauma increases intestinal proliferative activity. However, the morphologic changes do not unequivocally explain possible metabolic disturbances causing retarded intestinal wound healing.

Analysis of Variance↗

Expression of drug-metabolizing enzymes and P-170 glycoprotein in colorectal carcinoma and normal mucosa.

Resistance to chemotherapy is a significant problem in the treatment of colorectal carcinomas. To obtain insight into the mechanism of drug resistance, the expression of P-170 glycoprotein and biotransformation enzymes that are potentially able to contribute to drug resistance were investigated in paired samples of normal mucosa and tumors from 24 patients with colorectal cancer. In the tumors, glutathione S-transferase (GST) enzyme activity and content of GST-pi and P-170 glycoprotein were increased significantly compared with normal mucosa (P less than 0.03, P less than 0.003, and P less than 0.02, respectively). In contrast, GST-alpha and -mu, present in minor amounts compared with GST-pi, were downregulated in the tumor. Cytochrome P-450(4,5,6) and UDP-glucuronyltransferase (towards 4-nitrophenol and bilirubin) levels were significantly lower in the tumors (P less than 0.0001 and P less than 0.0002, respectively). Because decreased expression of cytochrome P-450 and increased levels of GST-pi and the P-170 glycoprotein have been implicated in (multi)drug resistance, these findings strongly suggest that in colorectal tumors the inherent resistance is multifactorial. Research to overcome this resistance should therefore be directed toward a combined treatment that eliminates all of these different mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomosesP6.

Collagen synthesis in intestinal anastomoses has been measured in rats after in vivo administration of cytostatics. The cytostatics were administered during 5 consecutive days either intravenously or intraperitoneally. On day 3 of the course the rats received both an ileal and a colonic anastomosis. The animals were sacrificed 3 and 7 days after operation. The cytostatics regimen used was a combination of 5-fluorouracil, bleomycin and cisplatinum in a dose of 10, 2 and 0.35 mg kg-1 day-1, respectively. In an additional group, a twice higher dose was given intraperitoneally. Three days after operation a severe inhibition of the collagen synthesis was observed in all the cytostatics treated groups, both in ileum and in colon. The effects of intraperitoneal administration were much more pronounced than those observed after an equal dose given intravenously. Seven days after operation the collagen synthesis in the intravenously treated groups was restored to the level of the control group. However, in the intraperitoneal groups the collagen synthesis in ileal anastomoses was still inhibited. Thus, cytostatics suppress collagen synthesis in intestinal anastomoses. The effect is more severe after intraperitoneal than after intravenous administration, confirming our earlier hypothesis that the former mode of administration comprises a higher risk for anastomotic integrity.

Anastomosis, Surgical↗