Biomedical subjects

A E Stenwig

Publications and source records attributed to A E Stenwig.

At least 19 recordsLinked to original sources

PubMed1992

Molecular genetic studies of tumor suppressor gene regions on chromosomes 13 and 17 in colorectal tumors.

BACKGROUND: In the majority of colorectal carcinomas, both copies of the tumor suppressor gene TP53 (tumor protein 53) are known to be inactivated. In contrast to a loss of tumor suppressor function, it has been suggested that an increased copy number of the RB1 gene is involved in the progression of these tumors. PURPOSE: To determine genetic alterations at chromosomes 13 and 17 in colorectal tumors, we have studied several loci on these chromosomes, with special focus on the RB1 and TP53 genes at both the level of DNA sequence and the level of gene expression. METHODS: Restriction fragment length polymorphism analysis was performed after alkaline Southern blotting of the DNA fragments and hybridization (in 7% sodium dodecyl sulfate and 0.5 M NaPO4) of the nylon membranes with multiprimed, radioactively labeled probes. Total RNA was extracted from tissue biopsy specimens by homogenization of the samples in guanidinium thiocyanate followed by separation in a CsCl gradient. By use of an image-processing system, x-ray film signals were measured densitometrically. Point mutations within the TP53 gene were detected by use of polymerase chain reaction (PCR) in combination with constant denaturant gel electrophoresis. Direct sequencing of PCR products revealed the exact nature of the mutations. Protein expression of TP53 was seen by immunostaining of sections from paraffin-embedded material using a mouse monoclonal antibody. The two-sided Fisher's Exact Test was used for statistical analysis. RESULTS: An increase in allelic copy number at 13q loci was seen in 10 (32%) of 31 tumors. In the majority of the cases, this increase probably reflected a change in the diploid status of chromosome 13; in some cases, however, only part of the 13q seemed to be involved. The RB1 gene showed an elevated level of RNA compared with the beta-actin signal. Fourteen (48%) of 29 tumors showed loss of heterozygosity at loci on 17p, and base mutations within the TP53 gene were seen in 14 (42%) of 33 tumors. RNA and protein analyses of TP53 revealed an increased level of expression in the tumors compared with normal mucosa. Allelic variations seen at 13q and 17p were not associated (P = .7). CONCLUSIONS: Our results suggest that, in addition to aneuploidy, gain of specific chromosome 13 sequences is involved in the tumorigenesis of the colon and rectum. In addition, they confirm the importance of TP53 mutations for the progression of such tumors and support the view that accumulation of events is more important than the order of events. The genetic changes observed at chromosome arms 13q and 17p seem to be independent of each other.

Adolescent↗

PubMed1992

Long-term survival in patients with follicular thyroid carcinoma. The Oslo experience: variations with encapsulation, growth pattern, time of diagnosis, sex, age, and previous thyroid surgery.

In 98 follicular thyroid carcinoma patients with a follow-up of 10-32 years, 10-year survival varied in subgroups from 15.5-63.4%. Survival with encapsulated primary tumors was 46.7%, compared to 26.9% in widely invasive tumors, and varied from 59.9-35.8% with growth pattern. In patients younger than 60 years of age at diagnosis 10-year survival was 68% of expected survival, compared to 32% in patients older than 60. Patients treated after 1970 had an improved survival of 24.2%. Thirty-one patients had previous thyroid operations for benign lesions. Review of histopathologic slides and medical records demonstrated follicular adenomas in 17 cases, and overlooked carcinomas in 11. Calculating survival from the first surgical intervention improved reported 10-year survival by 14.5%. Papillary carcinoma patients matched for age and sex had significantly better 10-year survival.

Adenocarcinoma↗

PubMed1992

Retroperitoneal surgery in patients with nonseminomatous testicular cancer and minimal residual tumor.

In the period 1980-1991, 78 patients with advanced nonseminomatous testicular cancer underwent retroperitoneal lymphadenectomy for post-chemotherapy residual masses less than 2 cm. To decrease the frequency of "dry ejaculation" in these patients with no or limited residual disease, the extent of dissection was reduced during the period, with bilateral dissections (49 cases, 1980-1986) being initially replaced by unilateral procedures (19 cases, 1983-1990) and subsequently by nerve-sparing techniques (10 cases, 1990-1991). As expected, a higher total number of lymph nodes was found in the retroperitoneal specimens after bilateral (44 (13-100)) than after unilateral (21 (7-35)) and nerve-sparing (18 (7-60)) procedures. The number of lymph nodes with pathological changes was low, with 3 (1-16) after bilateral, 2 (1-9) after unilateral, and 2 (1-4) after nerve-sparing operations. Histological examination revealed only necrosis/fibrosis in 65% of the patients, elements of mature teratoma in 28%, and remnants of viable malignant tumor in 6%. There were no major postoperative complications. "Dry ejaculation" was reported by 84% of the patients with bilateral operations, but was generally avoided after the unilateral (16%) and nerve-sparing (nil) procedures. After a mean follow-up of 83 (5-138) months, 6 patients have developed a recurrence, only one of them primarily in the retroperitoneal space. It is concluded that in patients with minimal residual retroperitoneal tumor, postchemotherapy lymphadenectomy using a unilateral or nerve-sparing technique seems to offer an effective therapeutic alternative with acceptable postoperative morbidity and preserved ejaculation.

Adolescent↗

PubMed1992

Deoxyribonucleic acid cytometry and histological findings before and after 125iodine implantation of primary prostate cancer.

Deoxyribonucleic acid (DNA) flow cytometry and light microscopy were performed in pre-radiotherapy and post-radiotherapy biopsies obtained from the primary tumor in 31 patients with prostate cancer. Radiotherapy was applied by means of transperineal 125iodine (125I) implantation. Of the patients 21 had pretreatment biopsies and in 19 of these biopsies also were performed 1 and/or 1 1/2 years after the 125I implantation. Posttreatment biopsies were available for DNA flow cytometry in 12 additional patients without pretreatment DNA flow cytometry assessment. Of the 21 pretreatment biopsies 7 were diploid, 6 tetraploid and 8 aneuploid. All 31 posttreatment biopsies were either tetraploid (21) or aneuploid (10). All 6 pretreatment diploid tumors became tetraploid after radiotherapy. At 1 and/or 1 1/2 years after 125I implantation residual tumors were found in 28 of 31 prostatic glands. The high frequency of nondiploid DNA stemlines 1 or more years after 125I implantation and the high rate of residual tumor leave some doubt about the radiocurability of prostate cancer by the chosen radiotherapy technique.

Biopsy↗

PubMed1992

High-dose methotrexate in the treatment of malignant mesothelioma of the pleura. A phase II study.

From 1984 to 1989, 63 patients with diffuse, malignant mesothelioma of the pleura were treated with 4-8 courses of high-dose methotrexate (HDMTX, 3 g total dose) and citrovorum factor rescue. There were 61 male and two female patients of median age 60 years. CT scan was performed before and after treatment and used for response evaluation. Of 60 patients evaluable for response, 37% showed partial or complete remission, 32% showed no change and 32% showed progressive disease. Median survival from start of treatment for all patients was 11 months, for 42 patients with the epithelial type 12 months, and for 20 patients with sarcomatous or mixed types only 5 months. Toxicity was acceptable, with only five patients (8%) terminating therapy due to toxicity. One toxic death occurred. We conclude that HDMTX is an active regimen in malignant pleural mesothelioma. The significantly shorter survival for patients with the sarcomatous or mixed subtypes indicates that further investigations on the activity of HDMTX in mesothelioma should be limited to patients with the epithelial subtype.

Dose-Response Relationship, Drug↗

PubMed1992

Is postchemotherapy retroperitoneal surgery necessary in patients with nonseminomatous testicular cancer and minimal residual tumor masses?

PURPOSE: At least one third of the patients with metastatic testicular cancer are rendered tumor-free by cisplatin-based chemotherapy. One may question, therefore, the routine use of postchemotherapy retroperitoneal lymph node dissection (RLND), especially if the residual masses are less than 20 mm in diameter. To define the role of such surgery, we analyzed the postchemotherapy histology in testicular cancer patients with minimal residual disease. PATIENTS AND METHODS: Seventy-eight patients with advanced nonseminomatous testicular cancer underwent RLND after three to four cycles of cisplatin- or carboplatin-based chemotherapy. In all patients, the largest diameter of the residual retroperitoneal mass was less than 20 mm. RESULTS: Complete fibrosis/necrosis was found in 51 patients, mature teratoma in 22, and vital malignant germ cell tumor in five. In two of the latter five patients, alphafetoprotein (AFP) had increased immediately before RLND. In the 76 patients with normal pre-RLND tumor markers, the presence of undifferentiated malignant teratoma (MTU) in the primary tumor and normal prechemotherapy tumor markers were independent parameters predicting complete fibrosis/necrosis, which was demonstrated in all 15 patients with these two pretreatment parameters. CONCLUSIONS: Postchemotherapy RLND can be omitted in patients with MTU in the primary tumor who have normal AFP/human chorionic gonadotropin (AFP/HCG) before chemotherapy and whose residual retroperitoneal mass is less than 20 mm in diameter. If the pre-RLND tumor markers are normal, RLND should be performed in all other patients with small residual masses, even in the presence of a normal computed tomography (CT) and particularly if regular follow-up of the patients is not guaranteed.

Adolescent↗

PubMed1992

Carcinoembryonic antigen in anal carcinoma.

Patients with squamous cell carcinoma of the anal canal occasionally present with an elevated level of carcinoembryonic antigen (CEA) in serum. The present study was performed to evaluate the clinical importance of this observation. Serum CEA was measured in 106 patients prior to chemo- and radiotherapy and during follow-up. Twenty patients had elevated serum CEA level before treatment. In 6 of 12 cases, serum CEA did not normalize after successful treatment and in 4 of 7 cases it rose no further despite progressive disease. CEA-positive tumours were more often poorly differentiated than CEA-negative tumours. There was no significant correlation between serum CEA, tumour CEA and prognosis. We conclude that measurement of serum CEA and staining of tumour CEA lack clinical importance.

Adult↗

PubMed1991

Post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. Is it necessary to resect all residual masses?

A total of 15 patients with advanced nonseminomatous testicular cancer underwent 2 sequential operations (4 in 1 patient) to remove residual masses after cisplatin-based combination chemotherapy. All patients had normal human chorionic gonadotropin and alpha-fetoprotein levels but persistent radiographic masses after chemotherapy. The operations included retroperitoneal lymph node dissection in 13 patients, thoracotomy in 15, hepatic resection in 3 and craniotomy in 1. Histological comparison of the specimens resected during post-chemotherapy operations 1 and 2 demonstrated different patterns in 7 of 15 patients. Of these 7 patients 4 had less favorable pathological features in the specimen removed during the second procedure. Residual malignant tumor or mature teratoma was found in at least 1 site in 12 of the 15 patients and only 3 had complete necrosis or fibrosis in both specimens examined. These data indicate the favorable impact of excising all post-chemotherapy tumor residuals in patients with advanced nonseminomatous testicular cancer. However, in patients with no teratomatous elements in the testicular tumor and complete necrosis or fibrosis in the initial post-chemotherapy operation specimen the probability of complete necrosis or fibrosis in remaining tumors appears to be high.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study.

From 1982 to 1989, 97 patients with extremity-localized, high-grade osteosarcoma were treated according to the T-10 protocol. Two thirds of the patients consisted of the near-complete national patient materials from Norway and Finland. Eighty patients (82%) received four courses of high-dose methotrexate (HD MTX, 8 to 12 g/m2) at weekly intervals as their only preoperative treatment, and 77 patients (79%) were assessable for histologic response grading according to Rosen et al (Cancer 49:1221-1230, 1991). Observed histologic response was no certain chemotherapy effect (grade I) in 21%, grade II effect in 62%, and grade III or IV effect in 17%. Nonresponders had significantly lower serum MTX concentrations after 24 and 48 hours than responders; the significance of the difference at 48 hours was maintained in a multivariate analysis. After a median follow-up of 45 months, projected 5-year overall and relapse-free survival for all patients were 64% and 54%, respectively. Patients with a good response to preoperative chemotherapy (grade III/IV) had a significantly better survival than grade I/II responders, despite a switch to postoperative cisplatin/doxorubicin chemotherapy in the latter group. These results were obtained in a largely nonselected group of patients. We conclude that a good initial chemotherapy effect is important for the final outcome in osteosarcoma, and that HD MTX alone is insufficient preoperative treatment for the majority of patients. The individual MTX excretion rate is of importance for tumor response, suggesting a dose-response relationship for HD MTX treatment.

Adolescent↗

PubMed1991

CT in primary malignant germ cell tumors of the retroperitoneum.

Malignant germ cell tumors may exist as a primary entity in the retroperitoneum. In a CT study of 14 males with this condition (2 seminomas and 12 non-seminomatous tumors) all masses were large, lobulated and of mixed density. Fat plane obliteration against adjacent structures was frequent. The aorta was embedded in 9 patients and the inferior vena cava was affected in 7, 2 of whom had signs of compromised caval blood flow. Distant metastases were found in the lungs (7 patients), liver (n=4), posterior mediastinum (n=3), and in brain and supraclavicular lymph nodes in one patient each. Serum biomarkers were elevated in 11 patients. An extragonadal germ cell tumor should be considered when CT of the abdomen reveals a large retroperitoneal mass with mixed density.

Adult↗

PubMed1990

Metastatic testicular cancer and extragonadal germ cell tumor presenting with neurological symptoms.

We present two patients with testicular cancer and extragonadal germ cell tumor respectively in whom neurological symptoms due to metastases preceded the correct diagnosis. Testicular cancer and extragonadal germ cell tumor are today curable malignancies even when distant metastases are present at diagnosis. The diagnosis of germ cell tumor should be considered whenever a young man presents with metastases of uncertain origin, and all histological specimens should be revised with the diagnosis of germ cell tumor in mind.

Adult↗

PubMed1990

Prognosis in patients with metastatic non-seminomatous testicular cancer.

155 patients with metastatic non-seminomatous testicular cancer were treated with cisplatin-based chemotherapy which in most cases was combined with surgery. The 5 year crude survival was 90% for all patients (98 patients with small volume disease: 97%; 32 patients with large volume disease: 91%; 25 patients with very large volume disease: 64%). High pre-chemotherapy serum tumour marker levels (AFP greater than 500 micrograms/l; and/or HCG greater than 1000 U/l) decreased the survival rates in all groups. Only 4 of 17 relapsing patients were rendered tumour-free by salvage chemotherapy. In a multivariate analysis, a pre-chemotherapy alpha-foetoprotein (AFP) level greater than 500 micrograms/l was associated with poor survival as was the presence of a retroperitoneal tumour greater than 10 cm, lung metastases greater than 3 cm and/or extrapulmonary hematogenous metastases. It is concluded that easily assessable clinical pre-treatment variables can be used to define high risk or low risk patients with metastatic testicular cancer. Treatment intensity should be adjusted in accordance to such prognostic factors.

Adolescent↗

PubMed1990

Is routine primary retroperitoneal lymph node dissection still justified in patients with low stage non-seminomatous testicular cancer?

We present 8 years' experience of primary retroperitoneal lymph node dissection (RLND) in 190 patients with low stage non-seminoma; 154 patients had clinical stage I (CSI) and 36 had clinical stage IIa (CSIIa) disease. Of the 154 patients with CSI tumours, 33 had increased serum AFP and/or HCG before RLND (CSIM+) and 121 had normal tumour markers (CSIM-). Retroperitoneal lymph node metastases (pathological stage II) (PSII) were found in 38 of 121 patients with CSIM-, in 19 of 33 patients with CSIIM+ and in 26 of 36 patients with CSIIa. In a multivariate analysis, the presence of small vessel infiltration (demonstrated in histological sections of the primary tumour) and a prolonged tumour marker half-life were predictive factors for PSII. These 2 factors enabled a group of non-seminoma patients with CSI disease to be identified who had a 15% risk of retroperitoneal tumour growth (low risk group) as compared with a high risk group where 60 to 70% of patients had retroperitoneal lymph node metastases. Relapses occurred in 7 of 107 patients with PSI and in 6 of 83 patients with PSII disease; in the latter group, 5 relapses developed before the start of routine adjuvant chemotherapy; 6% of patients developed major post-operative complications. In addition, "dry ejaculation" was the principal side effect following RLND (unilateral RLND: 20/132 patients; bilateral RLND: 50/54 patients). The comparative cost to the health service during the first year of follow-up was estimated for low risk non-seminoma patients with CSI subjected to RLND and for those in whom a surveillance policy was adopted. The latter approach was preferable. It was concluded that a surveillance policy should be followed in low risk non-seminoma CSI patients provided that frequent follow-up is possible. A more active policy is recommended in high risk patients (e.g. adjuvant chemotherapy without RLND). Nerve-sparing RLND may be considered in patients with CSIIa disease and negative tumour markers.

Adolescent↗

PubMed1990

Serum follicle stimulating hormone--predictor of cancer in the remaining testis in patients with unilateral testicular cancer.

In 10 of 13 patients with unilateral testicular cancer and subsequent invasive cancer or carcinoma in situ in the remaining testis, the follicle stimulating hormone (FSH) level was elevated after the first orchiectomy and before further treatment. In only 4 of 26 comparable control patients was the FSH level raised. This may be because elevated serum FSH often reflects disturbances in spermatogenesis and fertility, the latter being a known risk factor for testicular cancer. An elevated FSH level that occurs after orchiectomy for unilateral testicular cancer and before further treatment identifies patients at high risk of developing a tumour in the remaining testis.

Adolescent↗

PubMed1990

Management of patients with poor-prognosis nonseminomatous germ cell cancer.

The treatment and outcome of 57 patients with poor-prognosis metastatic nonseminomatous germ cell cancer were reviewed. The patients were treated between 1980 and 1986. Poor-prognosis patients were characterized by the presence of at least one of the following findings: (1) retroperitoneal tumor mass greater than 10 cm; (2) greater than 3 lung metastases, the largest being greater than 2 cm; (3) extrapulmonary, extralymphatic, metastases; and (4) extragonadal primary tumor. The intended treatment consisted of cisplatin-based combination chemotherapy followed by secondary surgery. From 1980 to 1983 a modified Einhorn regimen was used (cisplatin 100 mg/m2 per cycle; CVB). In case of unacceptable vinblastine toxicity, this drug was substituted by VP-16 (500 mg per m2 per cycle; BEP20). From October 1983 the intention was to replace at least 3 of the CVB/BEP20 cycles by BEP60 cycles (days 1-3: cisplatin 60 mg/m2, days 1-3: VP-16 120 mg/m2; days 1, 5, 15: bleomycin 30 mg). There were 33 patients in the CVB/BEP20 group and 24 patients in the BEP60 group. Two patients of the CVB/BEP20 group and 6 patients of the BEP60 group were not evaluable for response, but are included in the survival analysis. The reasons for exclusion from response evaluation were that these patients could not receive the intended chemotherapy in appropriate doses due to severely reduced pretreatment general condition or due to early death. Fourteen patients with multiple lung metastases but no other poor-prognosis criteria had a 93% survival indicating that they did not represent poor-prognosis germ cell cancer. After excluding these 14 patients, the 4-year survival was 58% for 19 CVB/BEP20 patients and 72% for BEP60 patients. This difference did not reach the level of statistical significance in this limited series. The introduction of high-dose cisplatin had thus not led to clearly superior treatment results as compared to CVB/BEP20.

Adolescent↗

PubMed1990

Prognosis of incidental prostatic cancer in Aust-Agder County, Norway.

The clinical significance of dividing incidental prostatic cancer into T0 focal (A1) and T0 diffuse (A2) is well documented, but criteria for the distinction vary considerably. Eighty-four patients with incidental prostatic cancer over a 5-year period comprise all newly diagnosed cases from an area of 94,000 inhabitants in the Aust-Agder County in Norway. This represents 13% of the patients operated upon for apparently benign prostatic hyperplasia. Of these patients, 80 with a mean age of 73.9 years did not receive any additional treatment after prostatectomy until progression (deferred treatment) and were followed up for 2-7 years. Three chips or less of well-differentiated cancer were defined as T0 focal (n = 18), all other cases were T0 diffuse (n = 62). Sixty-nine patients (86%) were free of progression. Eighteen patients died of causes unrelated to prostatic cancer. Progression occurred in 11 patients (14%) at a mean time interval of 39 months after diagnosis, and 3 patients died of prostatic cancer. Related to grade, progression occurred in 2% of the G1 tumors, in 25% of G2, and in 40% of the G3 tumors. When a tumor volume of 25% was chosen as level of distinction between T0 focal and T0 diffuse, 25 patients (31%) changed the stage to T0 focal without any impact on prognosis.

Aged↗

PubMed1990

Distribution of retroperitoneal lymph node metastases in patients with non-seminomatous testicular cancer in clinical stage I.

118 Patients with non-seminomatous testicular cancer (NSTC) in clinical stage I (CSI = no metastases by clinical, radiological and biochemical evaluation) underwent retroperitoneal lymph node dissection (RLND). The operation was done unilaterally (95 patients) in peroperatively tumor-free patients or in those with limited metastatic growth. In 23 patients with more extensive metastases, bilateral RLND was performed. Metastatic lymph nodes were found in 36 patients, and these patients received 3-4 cycles of a cisplatin-based combination chemotherapy. If no metastases were detected the patients had no further treatment. The 5-year disease-free survival rate was 100%. 8 of 82 patients without detected metastases in the operation specimen relapsed (all outside the retroperitoneal space), but were cured by salvage chemotherapy. Solitary metastases were found in 11 patients, whereas 25 patients had more than 1 metastatic lymph node. The size of the largest metastasis ranged from 0.3 to 40 mm. Metastases from right-sided tumors were detected at all levels of the lumbar region, predominantly to the right of the inferior vena cava and/or within the interaortocaval space. Left-sided tumors metastasized to the upper two thirds of the lumbar space, only rarely crossing the midline. This anatomical distribution of metastatic lymph nodes indicates that the presacral sympathetic nerve plexus and the sympathetic nerve fibers around the aortic bifurcation can be spared from extensive resection in the majority of patients with NSTC in CSI. Unilateral RLND or other nerve-sparing techniques are thus possible, preserving antegrade ejaculation in greater than 80% of the patients. This RLND represents a reasonable alternative to the 'surveillance' policy in NSTC.

Adult↗

PubMed1990

Prognostic factors in clinical stage I nonseminomatous germ cell tumors of the testis: multivariate analysis of a prospective multicenter study. Swedish-Norwegian Testicular Cancer Group.

Between 1981 and 1986, 279 consecutive patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT) of the testis underwent pathological staging (PS) with retroperitoneal lymphadenectomy (RPLND). Patients with retroperitoneal metastases (PS2) received adjuvant chemotherapy. The median follow-up time after RPLND was 50 months (range, 30 to 90). Clinical and histopathologic features were registered prospectively and analyzed for association with risk of having PS2, relapse despite pathological stage 1 (PS1) or the combined risk of either event, metastatic disease (MET). Seventy-five (26.9%) of the patients had PS2 disease, and 30 (14.7%) of the 204 PS1 patients relapsed, indicating that at least 105 (37.6%) of this CS1 population had subclinical MET at the time of orchiectomy. Four (1.4%) of the 279 CS1 patients died of testicular cancer. Multivariate analyses showed several variables to be significantly associated with outcome for the CS1 patients; vascular invasion in primary tumor and normal preorchiectomy serum alpha-fetoprotein (Pre-AFP) level indicated PS2 disease. If Pre-AFP was excluded from the model, the absence of teratoma or yolk sac elements in the primary tumor became significant predictors of PS2. Vascular invasion, absence of teratoma, and a short interval between orchiectomy and RPLND indicated increased risk of relapse in PS1 patients. Vascular invasion, normal Pre-AFP, absence of teratoma elements, and a short orchiectomy to RPLND interval were predictive of MET. Our results indicate that prognostic factors useful for stratification of CS1 patients with NSGCT to different treatment options may be established.

Chorionic Gonadotropin↗