Search PubMed⌕ Search

Biomedical subjects

J Jeekel

Publications and source records attributed to J Jeekel.

At least 163 records · Page 9Linked to original sources

Effect of perioperative blood loss and perioperative blood transfusions on colorectal cancer survival.

Results of various studies suggest that the perioperative administration of blood transfusions in cancer patients operated upon for cure is associated with a diminished patient survival. Furthermore, recent results from our laboratory indicate that blood loss may also be capable of promoting tumor growth. In order to elucidate these findings a retrospective study was initiated towards the survival of 164 patients with colorectal carcinoma, operated upon for cure, at the University Hospital, Rotterdam. In 117 patients who perioperatively received blood transfusions the 5-year survival was 68%, as compared to 80% in the non-transfusion group (P = 0.039; Wilcoxon). The 5-year survival in the group of patients with a perioperative blood loss exceeding 500 ml (n = 88) was 70%, as compared to 73% in the group with a blood loss of 500 ml or less (not significant). Multivariate analysis, adjusting for 11 relevant parameters, showed that only tumor stage and the administration of blood transfusions were significantly associated with a decrease in survival. It is concluded that perioperative blood transfusions adversely affect colorectal carcinoma survival in this group of patients. Perioperative blood loss was not a significant prognostic factor.

Adult↗

Absence of somatostatin receptors in human exocrine pancreatic adenocarcinomas.

Somatostatin receptor frequency was evaluated in 12 human exocrine pancreatic carcinomas taken after surgery. The tumors were analyzed by receptor autoradiography on tissue sections and by in vitro binding techniques on tumor homogenates. None of the tested human pancreatic carcinomas was shown to possess specific somatostatin receptors. In comparison, five single tumors taken from rats transplanted with the rat pancreatic adenocarcinoma CA 20948 were found to contain specific high-affinity somatostatin receptors. Also, human endocrine pancreatic tumors, i.e., two insulinomas, did contain somatostatin receptors under identical experimental conditions. These data confirm previous results with other tumors, documenting the absence of somatostatin receptors in highly malignant human carcinomas. They also may represent an explantation at the molecular level for the lack of therapeutic effect of somatostatin analogues such as SMS 201-995 seen in patients with advanced exocrine pancreatic carcinomas.

Adenocarcinoma↗

Combined treatment of colon adenocarcinoma in rats with tumor necrosis factor and the interferon inducer ABPP.

It is well documented that the antitumor capacity of tumor necrosis factor (TNF) can be enhanced by interferons (IFNs), notably IFN-gamma. The aim of this study was to investigate the efficacy of a combined treatment with TNF and the IFN-inducer 2-amino-5-bromo-6-phenyl-4-pyrimidinone (ABPP) on a transplantable colon carcinoma (CC531) in rats. The tumor was implanted under the kidney capsule of syngeneic rats; the tumors were removed a week after implantation and growth was assessed by weighing. The animals were treated with 1 microgram of TNF, given i.v. on days 0, 2, and 4; and with 250 mg/kg of ABPP, administered i.p. on days 0 and 1. The results of two separate experiments indicated that both TNF and ABPP had a significant inhibitory effect on tumor growth. Combined, the two agents were found to act additively. In the dosage used, TNF toxicity was mild, transient, and not influenced by ABPP.

Adenocarcinoma↗

Histological lesions associated with cyclosporin: incidence and reversibility in one year old kidney transplants.

To determine the type and reversibility of the long term effects of cyclosporin A, biopsy specimens were taken from 20 recipients of kidney allografts, twelve months after transplantation, and three months later, during which time azathioprine was substituted for cyclosporin A. Arteriolar IgM and complement deposits and tubular isometric vacuolisation associated with cyclosporin A treatment significantly regressed after stopping this drug one year after transplantation. Conversion to azathioprine was accompanied by an increase in mononuclear cell infiltrates and tubulitis despite an evident improvement in renal function. Nephrotoxicity as a result of cyclosporin A is common but can be reversed--at least partially.

Arteries↗

Prevention of CMV infection by screening for CMV antibodies in renal allograft recipients and their blood and kidney donors.

The influence of the cytomegalovirus (CMV) serostatus of blood and kidney donors on patient and graft survival was studied prospectively in 73 cadaveric renal graft recipients. Six out of 12 (50%) CMV seronegative recipients receiving a kidney from a CMV seropositive donor developed CMV disease, in contrast to none of 7 CMV seronegative donor/recipient combinations. Transmission of CMV with blood products to seronegative recipients was not observed in this study. A poor graft survival of 41% 3 years after transplantation was found in CMV seronegative recipients with CMV seropositive allograft donors, compared with an actuarial 3 year graft survival of 72% in the 7 CMV seronegative donor/recipient combinations. Six patients with graft failure had a CMV infection. This study, in accordance with other studies, suggests that selection of CMV seronegative renal allograft donors for CMV seronegative recipients will improve graft survival.

Adolescent↗

Local regional promotion of tumor growth after abdominal surgery is dominant over immunotherapy with interleukin-2 and lymphokine activated killer cells.

Various investigators have shown that tumor growth can be facilitated by surgery, that an operation can suppress immune functions, and that these phenomena may be related. With a murine intraperitoneal (i.p.) tumor model, we investigated whether an operation could promote tumor growth and, if so, whether this effect could be successfully overcome by immunotherapy with interleukin-2 (IL-2) and lympokine activated killer (LAK) cells. Treatment with IL-2 and LAK cells was highly effective in unoperated mice. When a laparotomy was done 4 days before i.p. tumor inoculation, tumor growth was enhanced in all experiments, and the effect of immunotherapy was completely abrogated. This effect was local regional; an incision on the back of the mice did not affect tumor growth or outcome of treatment. Tumor growth in the scar area was usually excessive. Furthermore, these effects were found to be temporary. Promotion of tumor growth and abrogation of IL-2 + LAK effects were seen only from 4 days to up to 2 weeks after laparotomy but were lost 5 weeks after surgery. These results suggest that growth factors present in healing wounds may cause promotion of tumor growth and are dominant over the effects of IL-2 and LAK cell therapy.

Animals↗

Anti-tumor activity of recombinant mouse tumor necrosis factor (TNF) on colon cancer in rats is promoted by recombinant rat interferon gamma; toxicity is reduced by indomethacin.

The activity and toxicity of rMuTNF, alone or combined with rat recombinant interferon gamma (rRIFN gamma), was tested in inbred WAG rats bearing a weakly immunogenic colon adenocarcinoma (CC531). The tumor was implanted s.c. or under the renal capsule. A single i.v. injection of 10 micrograms of rMuTNF in non-tumor bearers was lethal in 3 to 5 hr, whereas 2 micrograms was not. Doses of 1 microgram rMuTNF were well tolerated when given daily for one week. The most prominent toxic feature was hemorrhagic colitis which could be alleviated when rMuTNF was preceded by i.p. administration of 10 mg/kg indomethacin. Three intralesional injections of 10 micrograms rMuTNF on days 0, 10 and 15 into s.c. tumors (diameter 1-1.5 cm) led to a moderate retardation of growth in 20% of the cases. Combined with 10(5) units of rRIFN gamma, which on its own had no effect, the overall response rate (arrest of tumor growth or regression) was 50%. Two out of 20 tumors treated intralesionally with rMuTNF and rRIFN gamma regressed. The subrenal capsule assay was used to study the possible interference of indomethacin with the anti-tumor activity of rMuTNF. Tumor cubes of 6-8 mg were implanted under the renal capsule; the test was evaluated by weighing. Treatment with 10 mg indomethacin alone on days 0, 2 and 4 had no effect (40 +/- 8 mg vs. 48 +/- 13 mg in controls) whereas 2 micrograms of rMuTNF on the same days resulted in significant tumor inhibition (24 +/- 7 mg, p less than 0.001). The combined administration of 2 micrograms of rMuTNF and indomethacin had an effect similar to that of rMuTNF alone (25 +/- 9 mg). Under protection of indomethacin the rMuTNF dose was increased from 2 micrograms to 10 micrograms. However, this did not lead to further improvement of the results.

Adenocarcinoma↗

Ultrasound-guided percutaneous drainage of intra-abdominal abscesses.

The encouraging results of percutaneous abscess drainage (PAD) in simple intra-abdominal abscesses have led us to employ this method in patients with more complex abdominal inflammatory disease, such as those with multiple enteric communicating or multilocular abscesses and patients in whom the percutaneous approach requires puncture routes traversing uninvolved organs. Cure was achieved in 74 per cent of all patients (83 of 112 patients) who underwent PAD, but in only 50 per cent of patients with multiple intra-abdominal abscesses (n = 16), 50 per cent of patients with complex pancreatic inflammatory disease (n = 8) and 57 per cent of patients with complex intraparenchymal abscesses (n = 7). PAD contributed to cure in eight of nine patients with enteric communicating abscesses. The transhepatic route to perihepatic abscesses proved to be safe. Complications occurred in nine patients (8 per cent). No relationship was noted between the severity or number of complications and the indication for PAD. Of the 29 failures of PAD, 17 patients were cured by either surgical intervention (14 patients) or a second PAD (1 patient) or a combination of the two methods (2 patients). Twelve patients (11 per cent) died, eight from sepsis due to inadequate drainage. Frequent reassessment by ultrasonography and computerized tomography (CT) in patients with prolonged sepsis after PAD is mandatory. These results justify a place for PAD in the management of the often critically ill patient with complex abdominal inflammatory disease.

Abdomen↗

Fascia closure after midline laparotomy: results of a randomized trial.

Four techniques to close the fascia after midline laparotomy were compared in a prospective randomized multicentre trial. The four techniques were: interrupted closure with polyglactin; continuous closure with polyglactin; continuous closure with polydioxanone-s, and continuous closure with nylon. The early postoperative results in 1491 patients revealed an incidence of wound infection of 8.6 per cent and of wound dehiscence of 2.3 per cent with no statistically significant differences between the four techniques. We reviewed 1156 patients after 1 year. Wound pain was present in 9.7 per cent of the patients, statistically significantly more in the group closed with nylon (16.7 per cent). Suture sinuses developed in 3.5 per cent of the patients, statistically significantly more frequently in the nylon group (7.7 per cent). The total number of incisional hernias detected 1 year postoperatively was high (15.2 per cent) (interrupted polyglactin 16.9 per cent, continuous polyglactin 20.6 per cent, continuous polydioxanone 13.2 per cent and continuous nylon 10.3 per cent). The difference between nylon and continuous polyglactin is statistically significant. The results of this trial indicate that although nylon has the lowest incidence of incisional hernia it also is associated with more wound pain and suture sinuses.

Abdomen↗

Solitary malignant schwannoma of the pancreas: report of a case and ultrastructural examination.

Primary malignant schwannoma of the pancreas is rare. The reported patient, a 40-year-old white female, presented with obstructive jaundice and a large palpable mass in the upper abdomen. A Whipple procedure was performed. Electron microscopic examination of the tumor established the Schwann cell origin of the neoplasm by demonstrating basement membranes, junctional complexes, and interdigitating cytoplasmic extensions infested with basal lamina, dense neurosecretory-like granules, and axon-like structures. The inadequacy of light microscopic examination alone for establishing the diagnosis with certainty is discussed. Review of the literature revealed only one case of a malignant schwannoma of the pancreas that was not resected. This is the first report confirmed by ultrastructural examination.

Adult↗

Abrogation of the tumor promoting effect of allogeneic blood transfusion by polyadenylic-polyuridylic acid (poly A-poly U).

Studies from several centers have shown an immunosuppressive effect of surgical procedures, whilst others have shown blood transfusion in association with cancer surgery to have an adverse effect on ultimate prognosis. We have previously demonstrated enhanced growth of tumor metastases, in rats following allogeneic blood transfusion and surgery. Polyadenylic-polyuridylic acid (poly A-poly U) has been reported to stimulate immune responses. In this report, we have investigated the effectiveness of poly A-poly U as an adjuvant to blood transfusion and surgical procedures in BN rats bearing artificial lung metastases. Significantly reduced tumor growth was observed, following poly A-poly U adjuvant treatment. These results lead to serious contemplation of the use of this drug as adjuvant therapy in blood transfused and surgically treated patients.

Adjuvants, Immunologic↗

Synergistic antitumor activity of cyclophosphamide and ABPP in the treatment of established and advanced tumors in murine tumor models.

We have previously shown that the in vivo administration of ABPP, an interferon inducing pyrimidinone, generates activated killer cells that can lyse fresh tumor cells in vitro in 4-h 51chromium release assays. The administration of this agent however has no effect on established tumor. In this communication we show that ABPP, when used in combination with low or moderate doses of cyclophosphamide, can be quite effective against early established (day 3) tumor as well as against advanced, grossly visible (day 8-10) tumor in both the i.p. and pulmonary metastasis model. The synergistic antitumor activity of this chemoimmunotherapeutic regimen was very strong against immunogenic tumors but rather weak against nonimmunogenic tumors. Two treatment cycles were significantly more effective than one and multiple cycles even cured the majority of mice with established i.p. tumor. These experiments demonstrate the potential of chemoimmunotherapeutic regimens and highlight the efficacy of multiple treatment cycles.

Animals↗