Living renal donors: the Norwegian experience.
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Adult↗
Biomedical subjects
A Jakobsen
Publications and source records attributed to A Jakobsen.
Renal transplantation--the Norwegian model.
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Cadaver↗
Predictive and prognostic values of cancer-associated serum antigen (CASA) and cancer antigen 125 (CA 125) levels prior to second-look laparotomy for ovarian cancer.
CA 125 and cancer-associated serum antigen (CASA) were measured prior to second-look laparotomy (SLL) to investigate their predictive and prognostic values in 93 patients treated for epithelial ovarian cancer FIGO stage II, III, or IV. Residual tumor was diagnosed at the SLL in 58 patients (62%). The optimal cutoff level was 15 U/ml for CA 125 and 8 U/ml for CASA. Using these levels, the sensitivity for detection of residual tumor was 40% for CA 125 and 22% for CASA. The combined use of the markers resulted in a sensitivity of 47% (diagnostic gain 6.9%; 95% confidence interval (CI), 0.14-13.44%). Microscopic tumor volumes were equally diagnosed by CASA and CA 125. The independent prognostic value of CA 125 (RR = 2.6; 95% CI, 2.0-3.2) and CASA (RR = 2.2; CI, 1.5-2.9) was established by means of Cox regression analysis of the covariation between survival, age, FIGO stage, histopathology, tumor grade, and bulk of residual tumor at the primary operation and CA 125 and CASA before the SLL. In conclusion, we found that CASA could supplement CA 125 measurement prior to SLL and reduce the number of SLLs. Furthermore, CASA had an independent prognostic value for survival which may be used together with other information in the planning of further treatment of the individual patient.
Adult↗
The possible role of ultrasound in early cervical cancer.
The value of preoperative ultrasonography to detect lymph node metastases in patients with early cervical carcinoma (stage IB-IIA) was investigated in 111 patients. Comparison was made between ultrasound and the operative histopathologic findings in 109 patients and with fine-needle biopsy in 2 patients. The positive predictive value was 71%, and the negative predictive value was 84%. Sensitivity was 23%, specificity was 98%. Lymph node metastases were found in 19% (21 patients) by operative histopathologic examination; these patients received subsequent radiotherapy. The rest, 92 patients with no lymph node metastases at Meigs' operation, were followed by abdominal and transvaginal ultrasonography as well as clinical examination at 6, 9, 12, 18, 24, 36, and 48 months postoperatively to detect recurrences. The recurrence rate was 9.8%. Ultrasound alone detected only one recurrence in an asymptomatic patient. We conclude that ultrasonography is not reliable in the preoperative detection of lymph node metastases. Moreover, ultrasound examination presents no advantage over clinical examination in early detection of asymptomatic recurrent cervical cancer after radical hysterectomy.
Adult↗
A comparison of survival and side effects in two periods with a different approach to radical hysterectomy as treatment of cervical cancer stages Ib and IIa.
The study compares survival and complications during two periods with a different approach to radical hysterectomy as treatment of cervical cancer stages Ib and IIa. Group A included 128 patients operated during the years 1983-87. In that period 5 of the patients who were offered radical hysterectomy had cervical cancer stage IIa. Group B included 135 patients operated during the years 1988-91. In that period 7 of the patients who were offered radical hysterectomy had cervical cancer stage IIa. Considering stage 1b separately, the frequency of operation was raised from 52 (123/237) to 87% (128/148). A 5-years crude survival rate of 85% and 88% was observed in the two groups. The mortality rate was zero in both periods and no fistulae occurred. There were no significant increase in morbidity or length of hospitalization. In the elderly patients over sixty years a significant increase in minor postoperative complications and hospitalization more than 2 weeks were seen. The conclusion is that the frequency of radical hysterectomy as treatment of cervical cancer stage Ib can be raised from 52% to 87% without any noticeable influence on survival or complication rate.
Adenocarcinoma↗
Kidney transplantation in patients older than 70 years of age.
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Adolescent↗
A phase II trial of ifosfamide, 5-fluorouracil, and leucovorin in recurrent uterine cervical cancer.
Thirty patients with recurrent squamous cell carcinoma of cervix uteri no longer amenable to control with surgery and/or radiotherapy were treated with a combination of ifosfamide, 5-fluorouracil, and Leucovorin every 4 weeks. The response rate was 53% (complete response, 33%; partial response, 20%). Response rates outside and inside irradiated area were 68 and 27%, respectively. The median progression-free interval was 7 months, and the median overall survival was 12 months. Adverse effects included primarily leukopenia, and dose reduction was necessary in 18 patients (60%). The present combination is active in the treatment of recurrent cervical cancer with a high response rate. The long-term survival is however still unsatisfactory.
Adult↗
The value of bone marrow examination in small cell carcinoma of the lung.
Of 668 consecutive patients with SCLC, 472 underwent bone marrow examination for staging. In 330 patients a triple examination (sternal aspiration, iliac crest aspiration and biopsy) was performed, otherwise a single procedure. Bone marrow infiltration (MI) was found in 37% of the patients with extensive disease, and the frequencies of a positive finding in single and triple examination were not statistically different. In the group having triple examination performed iliac crest aspiration alone disclosed MI in 32%. When all three procedures were included still more patients with MI were found (42%) but the two values were not significantly different. In 6.6% of patients who would have been classified as 'limited' did bone marrow examination change the stage to extensive disease. Based on these results we recommend iliac crest aspiration, but not triple examination with iliac crest biopsy, in the staging of SCLC.
Biopsy, Needle↗
[Terminal kidney failure, uremia care and kidney transplantation].
In the Nordic countries, the annual figures for new patients scheduled for renal replacement therapy (i.e., dialysis or kidney transplantation) are 49 (Denmark), 55 (Finland), 65 (Norway) and 99 (Sweden) per million of the population (pmp). Some 40-50 of those patients are medically eligible for transplantation. If the transplant rate of the individual transplant centre or country is less, the waiting list will increase, as they do at some of the Nordic centres. The annual rate of transplants from living related donors, including spouses, varies from almost zero in Finland to nearly 20 pmp in Norway. The average age of recipients has increased with the increasing age of patients accepted for dialysis. Of the Nordic countries, Norway has the highest acceptance rate of patients above the age of 70, whereas dialysis is the preferred treatment for most of the elderly patients in the other Nordic countries. During the period 1989-93, death with a functioning kidney accounted for nearly half the graft losses in the Norwegian transplant population, and graft rejection for 37 percent. Cardiovascular disease was a predominant cause of death.
Adult↗
[Cancer following organ transplantation].
Organ transplantation is followed by an increased risk of cancer. Analysis of series of transplanted, and thus immunosuppressed patients, enables the risk factors associated with this treatment to be identified, and oncogenic mechanisms in general to be investigated. In most recent cancer studies where correct epidemiological methods have been used, the incidence of cancer among transplanted patients was found to be 3-5 times that in the general population. This was the case for most types of tumours, though the distribution was uneven with an over-representation of lip, cervical, vulvar, urological and skin cancer and lympho-proliferative disorders, most of which appear early after transplantation, except for skin cancer which appears later but increases in incidence with time. The increase in the incidence of cancer appears to apply to all kinds of organ transplantation, though so too does our knowledge of possible risk factors and oncogenic mechanisms in general. For many of the tumour types there would appear to be a connexion with virus infection, which opens up avenues of research regarding prophylaxis and treatment.
Humans↗
State of the art--kidney transplantation.
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Animals↗
A prospective randomized comparison of 6 and 12 cycles of cyclophosphamide, adriamycin, and cisplatin in advanced epithelial ovarian cancer: a Danish Ovarian Study Group trial (DACOVA).
Two hundred-two patients with FIGO stages III and IV epithelial ovarian cancer were randomized to 6 or 12 cycles of cyclophosphamide, Adriamycin, and cisplatin (CAP). Patients in complete clinical response underwent a second-look laparotomy, 1 month after cessation of chemotherapy. Patients randomized to 6 cycles and found to be in partial remission at second-look were to receive a further 6 cycles of CAP. Rate of complete pathological response was 23% for 6 cycles of CAP and 25% for 12 cycles; the median survival was 23 months for 6 cycles and 27 months for 12 cycles, and 3-year survival was 29% for 6 cycles and 35% for 12 cycles. None of these differences were statistically significant. Fifty-four patients randomized to 6 cycles were found to be in partial surgical remission at second-look laparotomy, and 24 of these patients agreed to a further 6 cycles and a third-look laparotomy. Six of these 24 patients had a complete pathological response at third-look, improving the complete response rate to 28% in those originally randomized to 6 cycles. However, 3 of these patients all had macroscopic tumors removed at second-look, and two had microscopic disease at second-look. Among patients achieving complete response mean cumulative doses in the CAP 6 cycle group were approximately 50% of those in the CAP 12 cycle group. However, when all patients were considered, this difference was only approximately 15% owing the continuation of chemotherapy in the partial responders of the 6 cycle group and early stopping for chemotherapy in the CAP 12 cycle group due to toxicity or progression. Patients in complete pathological response also showed similar survivals for 6 and 12 cycles. In conclusion, the study did not show a correlation between mean cumulative doses and complete pathological response and survival.
Aged↗
Aortoiliac reconstruction in preparation for renal transplantation.
Aortoiliac angiography has always been an integral part of the pretransplantation work-up of renal transplant candidates in Norway. The present study was undertaken to investigate the value of this routine. Based on the angiograms of approximately 1400 patients evaluated for renal transplantation during the 7-year period 1984-1991, 26 were found to have aortic and/or iliac atherosclerosis requiring pretransplant vascular reconstruction. Fifteen of the 26 patients had aneurysm of the abdominal aorta and 11 had extensive aortoiliac occlusive disease. A prosthetic graft was inserted in 25 patients and endarterectomy of the aortic bifurcation was performed in one. The cause of death was coronary heart disease in four of six patients who died before, and in one patient who died after, transplantation. Sixteen patients received a renal transplant while four patients are still on the waiting list. Fifteen of the recipients are alive, 14 with functioning renal transplants. The low yield of patients below 40 years of age requiring vascular reconstruction calls into question the routine use of angiographic investigation of renal transplant candidates below this age. However, we recommend this routine for the higher age groups because it often provides the surgeon performing the transplantation with valuable information. Aortoiliac reconstruction as preparation for renal transplantation is advocated when atherosclerosis of a degree that may preclude transplantation is found. Because of the high risk of myocardial infarction in these patients, one must be especially aware of coronary atherosclerosis when evaluating patients for this procedure.
Adult↗
A limited sampling method for estimation of the carboplatin area under the curve.
A limited sampling method for estimation of the carboplatin area under the curve (AUC) from one or two plasma concentration determination is presented. The model was conceived and developed using 43 pharmacokinetic studies in 15 patients with ovarian cancer (model data set) who received carboplatin in combination with cyclophosphamide. Linear regression analyses comparing the AUC and the drug concentration at a single time point (0.25-10 h after the end of the infusion) as calculated from the fitted exponential equations gave correlation coefficients as high as 0.97, with maximal correlations falling within the interval of 2-3.25 h. The model was validated prospectively in 9 patients with ovarian cancer (validation data set) who received the same treatment as did the model data set (21 pharmacokinetic studies), testing the equation AUC = 0.52 x C2.75 h + 0.92. Observed and estimated AUCs were correlated in the validation data set (r = 0.91). The mean predictive error (MPE% +/- SE) was -4.4% +/- 3.1% and the root mean squared error (RMSE%) was 13.9%. Multiple regression analysis revealed that adding a second sample drawn at 0.25 h (AUC = 0.053 x C0.25h + 0.401 x C2.75h + 0.628) improved the MPE% to -2.2% +/- 2.1% and the RMSE% to 9.4% (r = 0.96). We conclude that the carboplatin AUC can be estimated from a single plasma sample at 2.75 h or, more precisely, from two plasma samples at 0.25 and 2.75 h. The methods described may prove to be a handy tool for the calculation of approximate AUCs in trials of a size that would discourage detailed pharmacokinetic studies.
Antineoplastic Combined Chemotherapy Protocols↗
A limited sampling method for estimation of the etoposide area under the curve.
A limited sampling method for estimation of the etoposide area under the curve (AUC) is presented. The method was developed and validated in 23 patients (42 pharmacokinetic studies) with small-cell lung cancer (SCLC), limited disease. The patients received 100 mg/m2 etoposide as a 90-min intravenous infusion in combination with carboplatin, allowing for etoposide dose modification at a following course (25% increase or decrease) due to high or low nadir values for leukocytes or thrombocytes. Of the 42 pharmacokinetic studies, 27 were used in the model development and 15 were used in the model validation. Single regression analyses of the AUC versus the fitted concentrations for the model data set were performed at several time points. The analyses demonstrated high and essentially identical correlation coefficients in the interval between 2 and 21 h, with a maximal value of 0.96 being recorded at 4 h. Multiple regression analysis was then performed using fitted concentrations corresponding to 0.08-21 h. The best model for one sample was AUC = 1.01 x (dose level divided by 100 mg/m2) + 799 x C4 h, that for two samples was AUC = 1.43 x (dose level divided by 100 mg/m2) + 544 x C4 h + 1756 x C21 h, and that for three samples was AUC = 0.07 x (dose level divided by 100 mg/m2) + 110 x C5 min + 474 x C4 h + 1759 x C21 h. Not unexpectedly, the model validation revealed that the one-sample model was less precise than the two- or three-sample model [percentage of root mean squared error (RMSE%) = 11.6%, 7.1%, and 5.4%, respectively]. All models proved to be unbiased in the validation [percentage of mean predictive error (MPE%) +/- SE = 4.2% +/- 11.0%, 7.9% +/- 6.1%, and 6.3% +/- 5.3%, respectively]. The models were subsequently validated in 14 pharmacokinetic studies of patients with metastatic germ-cell tumours who were receiving combination chemotherapy with cisplatin and bleomycin plus 100 mg/m2 etoposide as a 90-min infusion. The RMSE% was 13.4%, 10.8%, and 9.0% and the MPE% +/- SE was -1.0% +/- 11.9%, 1.7% +/- 10.5%, and 2.7% +/- 7.9% for the one-, two-, and three-sample models, respectively. The limited sampling methods presented herein may prove to be a most valuable tool for therapeutic drug monitoring in regimens in which etoposide is given in combination with carboplatin or with cisplatin and bleomycin.
Antineoplastic Combined Chemotherapy Protocols↗
Prediction of lymph node metastases in patients with early squamous cell carcinoma of the cervix uteri by histopathological grading and flow cytometry.
The present study comprises a retrospective investigation of 126 patients with stage IB squamous cell carcinoma of the cervix, and a similar prospective investigation of 53 patients with stage IB and 6 patients with stage IIA disease. Tumour biopsies from these patients were analysed by means of flow cytometry and a semiquantitative histological grading system. The study showed that a combination of a low tumour cell DNA index and a low score value of the grading system indicated a very low risk of regional lymph node metastases (0% lymph node metastases in patients with low scores vs. 24-46% metastases in patients with high scores, P < 0.001). In order to study the reproducibility of the histological grading 20 randomly selected cases were studied blindly by three of the participating pathologists and after discussion of the grading criteria. A kappa coefficient of 722 demonstrated a substantial agreement between the observers. These results suggest that by combining flow cytometry with semiquantitative histological grading, a subgroup of patients with early squamous cell cancer of the cervix uteri may be selected that could be sufficiently treated with simple hysterectomy instead of radical hysterectomy including lymphadenectomy, which, in many oncology centres, is the standard treatment of this patient category.
Carcinoma, Squamous Cell↗
Surveillance following orchidectomy for stage I seminoma of the testis.
From 1985 to 1988, 261 unselected patients entered a nationwide Danish study of surveillance only for testicular seminoma stage I. The median follow-up time after orchidectomy was 48 months, range 6-67 months. 49 patients relapsed (19%). Sites of relapse were paraaortic lymph nodes in 41 patients, pelvic lymph nodes in 5, inguinal lymph nodes in 2 and lung metastases in 1 patient. The median time to relapse was 14 months, range 2-37 months. The 4-year relapse-free survival was 80%. 37 of the relapsing patients (76%) had radiotherapy as relapse treatment. Of these patients, 4 (11%) had a second relapse and received chemotherapy. 1 died of disseminated seminoma. Of the relapsing patients, 12 (24%) had chemotherapy as relapse treatment because of bulky (11 patients) or disseminated disease (1 patient). None of these patients have had a second relapse. However, 2 patients died of infection due to chemotherapy-induced neutropenia. Thus, there have been three seminoma-related deaths (1.1%). The testicular tumour size had an independent prognostic significance. The 4-year relapse-free survivals were 94, 82 and 64% for tumours < 3, 3 to < 6 and > or = 6 cm, respectively. Patients with tumours > or = 6 cm will now be given prophylactic radiation treatment, whereas we will continue to use surveillance only after orchidectomy for patients with tumours < 6 cm.
Adult↗
Radiotherapy for gynecologic cancer.
The past year has not seen any breakthroughs in radiation treatment of gynecologic cancer. In reference to cervix cancer, important contributions concerning side effects and the role of radiosensitizers were published. The lack of randomized trials dealing with adjuvant radiotherapy is obvious. Improvement based on technical progress can be expected. For ovarian cancer, an important review about whole abdominal irradiation as adjuvant therapy was published. The long-term complication rate of whole abdominal irradiation is acceptable, but whether adjuvant whole abdominal irradiation has an effect upon survival superior to that of chemotherapy is still discussed. Combined treatment with chemotherapy and radiation therapy for advanced ovarian cancer is feasible, but there is no proof that the addition of radiotherapy improves survival. Literature about endometrial cancer was scarce in 1992 and did not contribute to the major question: Does adjuvant radiotherapy have any effect in endometrial cancer?
Endometrial Neoplasms↗