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Biomedical subjects

S L Johansson

Publications and source records attributed to S L Johansson.

At least 19 recordsLinked to original sources

Bladder carcinoma with lymphoepithelioma-like differentiation: a report of 9 cases.

PURPOSE: Lymphoepithelioma-like carcinoma of the bladder is rare with only 14 cases reported to date. We report 9 additional cases with long-term followup. MATERIALS AND METHODS: All 713 patients with an initial diagnosis of bladder tumor in western Sweden from 1987 through 1988 were prospectively registered and followed. A clinical and histopathological review was performed on 816 bladder tumors from the files of the oncology department treated between 1962 and 1989. RESULTS: Of 9 patients with stages T2M0-T3M0 cancer treated with locoregional therapy 6 with either pure or predominant lymphoepithelioma-like carcinoma pattern had no evidence of disease after a median observation of 4 years (range 1 to 18) and 3 with focal lymphoepithelioma-like carcinoma pattern died of disease after 9 to 68 months. CONCLUSIONS: Lymphoepithelioma-like carcinoma is diagnosed in less advanced stages and has a more favorable long-term prognosis than other types of undifferentiated invasive carcinomas of the bladder. Our data and review of the literature suggest that lymphoepithelioma-like carcinoma should be treated stage by stage like other bladder carcinomas.

Aged

Detection of DNA adducts by 32P postlabeling following chronic exposure of rats to snuff.

A surgically created canal was used as a reservoir for instillation of snuff into the lower lip of rats for 10 weeks. DNA was isolated and digested with micrococcal nuclease/spleen phosphodiesterase. Polar DNA adducts were detected in all tissues examined when digests were fractionated by high performance liquid chromatography (HPLC), 32P postlabeled, 3' dephosphorylated and analyzed by two-dimensional thin layer chromatography (TLC). DNA adducts derived from aromatic carcinogens were not detected when digests were 32P postlabeled and analyzed by four-dimensional thin layer chromatography. These results suggest that non-aromatic agents initiate carcinogenesis following exposure to snuff. The adduction to DNA in organs of the gastrointestinal tract and the kidneys indicates that snuff usage results in systemic exposure to carcinogens and may contribute to the incidence of neoplasms in organs outside the oral cavity.

Animals

Chromosomal anomalies in a case of proliferative myositis.

Proliferative myositis, a reactive lesion similar to proliferative fasciitis and nodular fasciitis, has only been cytogenetically described in one other report to date. This previously described case showed trisomy 2. Cytogenetic analysis and fluorescence in situ hybridization (FISH) of a proliferative myositis lesion in the present study did not reveal trisomy 2 but the following clonal translocation was observed: 46,XX,t(6;14)(q23;q32).

Chromosomes, Human, Pair 14

Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators.

Cancer is a disease that begins with mutation of critical genes: oncogenes and tumor suppressor genes. Our research on carcinogenic aromatic hydrocarbons indicates that depurinating hydrocarbon-DNA adducts generate oncogenic mutations found in mouse skin papillomas (Proc. Natl. Acad. Sci. USA 92:10422, 1995). These mutations arise by mis-replication of unrepaired apurinic sites derived from the loss of depurinating adducts. This relationship led us to postulate that oxidation of the carcinogenic 4-hydroxy catechol estrogens (CE) of estrone (E1) and estradiol (E2) to catechol estrogen-3,4-quinones (CE-3, 4-Q) results in electrophilic intermediates that covalently bind to DNA to form depurinating adducts. The resultant apurinic sites in critical genes can generate mutations that may initiate various human cancers. The noncarcinogenic 2-hydroxy CE are oxidized to CE-2,3-Q and form only stable DNA adducts. As reported here, the CE-3,4-Q were bound to DNA in vitro to form the depurinating adduct 4-OHE1(E2)-1(alpha,beta)-N7Gua at 59-213 micromol/mol DNA-phosphate whereas the level of stable adducts was 0.1 micromol/mol DNA-phosphate. In female Sprague-Dawley rats treated by intramammillary injection of E2-3,4-Q (200 nmol) at four mammary glands, the mammary tissue contained 2.3 micromol 4-OHE2-1(alpha, beta)-N7Gua/molDNA-phosphate. When 4-OHE1(E2) were activated by horseradish peroxidase, lactoperoxidase, or cytochrome P450, 87-440 micromol of 4-OHE1(E2)-1(alpha, beta)-N7Gua was formed. After treatment with 4-OHE2, rat mammary tissue contained 1.4 micromol of adduct/mol DNA-phosphate. In each case, the level of stable adducts was negligible. These results, complemented by other data, strongly support the hypothesis that CE-3,4-Q are endogenous tumor initiators.

Animals

Inflammatory response of mouse skin exposed to the very potent carcinogen dibenzo[a,l]pyrene: a model for tumor promotion.

The potent carcinogenicity of dibenzo[a,l]pyrene in mouse skin is associated with an inflammation unique among polycyclic aromatic hydrocarbons and expressed as erythema. The time course of erythema and the associated histological events in the skin of female SENCAR mice were determined after a single application of 6.25-200 nmol dibenzo[a,l]pyrene or selected metabolites. Dibenzo[a,l]pyrene and dibenzo[a,l]pyrene-11,12-dihydrodiol, precursor to the bay-region diol epoxide, induced an erythema first present 5-6 days after treatment. Dibenzo[a,l]pyrene-8,9-dihydrodiol and other dibenzo[a, l]pyrene metabolites, however, did not induce erythema. These findings suggest a central role for the bay-region diol epoxide in the induction of the observed inflammation. The intensity and duration of erythema were dose-dependent, whereas the delayed appearance of erythema was constant and dose-independent. These results suggest induction of an immune hypersensitivity by dibenzo[a, l]pyrene and its 11,12-dihydrodiol. Histological changes in the skin were consistent with a contact hypersensitivity reaction and included, in association with erythema, epidermal hyperplasia and the presence of mononuclear leukocytes in the dermis. Animals were tested for dibenzo[a,l]pyrene-induced contact hypersensitivity. Female SENCAR mice were treated with a single dermal application of dibenzo[a,l]pyrene or 7,12-dimethylbenz[a]anthracene. Five days later, the animals were challenged with a single application of dibenzo[a,l]pyrene or 7,12-dimethylbenz[a]anthracene to the ear pinna. Ear swelling exhibited features of a contact hypersensitivity reaction, including (1) delayed appearance after challenge, (2) noninducibility in animals not previously exposed to chemical sensitizer, and (3) chemical specificity. The results suggest that dibenzo[a,l]pyrene induces, via its bay-region diol epoxide, a contact hypersensitivity reaction that may promote tumor development and thereby enhance carcinogenic potency.

Administration, Cutaneous

The importance of the depth of invasion in stage T1 bladder carcinoma: a prospective cohort study.

PURPOSE: We studied the depth of invasion in the lamina propria in all patients with primary stage T1 bladder cancer in a geographical region and related the findings to the long-term prognosis. MATERIALS AND METHODS: All 121 primary stage T1 tumors diagnosed in western Sweden between 1987 and 1988 were analyzed with respect to the depth of invasion in relation to the lamina muscularis mucosae. All clinical records were reviewed in 1994 and 1995. RESULTS: More than 90% of the histopathological specimens could be separated into superficially (pT1a) or deeply (pT1b) invasive stage T1 tumors. Grade 3 tumors were significantly more common among patients with stage pT1b disease (79 versus 40%, p < 0.001). Patients with stage pT1b grade 3 cancer had a higher progression rate (58 versus 36%, p > 0.05) and an almost doubled risk of dying of bladder carcinoma compared to those with stage pT1a grade 3 disease (45 versus 23%, p > 0.05). Carcinoma in situ at the primary operation was associated with an impaired prognosis in patients with grade 3 tumors regardless of the depth of invasion in the lamina propria. CONCLUSIONS: The prognosis is poor in patients with deep lamina propria invasion (stage pT1b) treated with transurethral resection alone. Patients treated with radical cystectomy had excellent survival regardless of the depth of invasion in the lamina propria. Radiotherapy was associated with poor survival.

Aged

Ovary-intact, but not ovariectomized female ACI rats treated with 17beta-estradiol rapidly develop mammary carcinoma.

We have examined the ability of 17beta-estradiol (E2) to induce development of mammary cancers in the female ACI rat. Continuous treatment with E2, delivered through release from s.c. Silastic tubing implants containing 27.5 mg crystalline hormone, resulted in rapid development of palpable mammary tumors in ovary-intact ACI rats. In a population of 21 E2-treated rats, palpable tumors were first observed following 99 days treatment and 100% of the treated population developed tumors within 197 days. The median and mean times to appearance of first palpable tumor were 143 and 145 days respectively. All mammary tumors were classified as carcinomas and invasive features were observed. Circulating E2 levels in the treated animals at the time of sacrifice averaged 185 pg/ml serum. Mammary tumors were not observed in ovary-intact female ACI rats that were not treated with E2. This is the first report indicating that this naturally occurring estrogen is capable of inducing mammary cancers in the ACI rat strain. Mammary carcinoma did not develop in a population of 11 ovariectomized female ACI rats treated with E2 for a period of 140 days. Circulating E2 levels in the treated ovariectomized animals averaged 207 pg/ml. These data indicate that the ovary modulates estrogen-mediated mammary carcinogenesis in this rat strain. Both ovary-intact and ovariectomized female ACI rats displayed similar susceptibilities to E2-induced pituitary tumors and hyperprolactinemia. Pituitary weight was increased 6.0-fold in ovary-intact ACI rats and 5.3-fold in ovariectomized female rats. Circulating prolactin levels averaged 2318 ng/ml in E2-treated, ovary-intact rats and 2285 ng/ml in E2-treated, ovariectomized ACI rats. These data indicate that estrogen-induced hyperprolactinemia is not the sole factor leading to development of mammary cancers in the E2-treated ACI rat.

Animals

Primary signet ring cell carcinoma of the bladder: a report on 10 cases.

Primary signet ring cell cancer of the urinary bladder is a rare tumour with some 70 cases reported to date. We report on ten additional cases with long-term follow-up. All 713 primary bladder tumours in western Sweden diagnosed during a 2-year period were prospectively registered and followed and all the histopathological material reviewed. A clinical and histopathological review of 816 bladder tumours from the files of the Oncology Clinic treated between 1962 and 1989 was performed. An incidence of primary signet ring cell carcinoma of 0.6% was found. Three out of five patients who were worked up as a result of an occasional episode of macroscopic haematuria were tumour-free 2, 5 and 14 years, respectively, after radical transurethral resection. Seven patients died of the disease after 5-26 (median 19) months. Our study and a review of the literature indicate that the majority of patients with primary signet ring cell carcinomas are diagnosed at an advanced stage and survival is poor. However, some patients with small tumours at diagnosis were tumour-free after transurethral resection. Radiotherapy was ineffective in most cases. Systemic chemotherapy is of no benefit.

Adult

Long-term followup of a bladder carcinoma cohort: questionable value of radical radiotherapy.

PURPOSE: We studied the outcome of radical radiotherapy for bladder carcinoma in all patients from a well-defined region. MATERIALS AND METHODS: All 701 cases with a new bladder carcinoma between 1987 and 1988 in Western Sweden were prospectively documented and followed until 1994. Between 1987 and 1994, 74 of the 701 patients (mean age 73 years, range 54 to 88) were treated with external beam radiotherapy (60 Gy. or more). RESULTS: At least 84% of the patients had persistent tumor, a local recurrence or a symptomatic contracted bladder after external beam radiotherapy. Seven patients (9.5%) died of early or late treatment related complications. Of only 8 long-term survivors 6 had undergone radical transurethral resection before external beam radiotherapy. CONCLUSIONS: Full dose external beam radiotherapy in patients with bladder carcinoma was associated with high local recurrence and serious complication rates. It must be questioned whether elderly patients actually benefit from full dose radiotherapy.

Aged

Long-term followup of all patients with muscle invasive (stages T2, T3 and T4) bladder carcinoma in a geographical region.

PURPOSE: We studied the relationship between long-term survival and treatment of stages T2, T3 and T4 bladder carcinoma in an unselected patient population. MATERIALS AND METHODS: A total of 680 patients with the initial diagnosis of bladder carcinoma in 1987 to 1988 in Western Sweden was prospectively registered and followed until 1994. Of these patients 107 had stage T2 to T3 and 41 had stage T4 disease. RESULTS: Of the patients with stage T2 to T3 disease 30 (mean age 66) underwent radical cystectomy, 33 (mean age 75) full dose radiotherapy and 44 (mean age 81) nonradical therapy (mainly transurethral resection of the bladder). The 5-year crude survival rates were 33, 15 and 14%, respectively. Of the patients with stage T4 disease 6 (mean age 61) underwent radical cystectomy, 9 (mean age 73) full dose radiotherapy and 26 (mean age 81) nonradical therapy (mainly transurethral resection of the bladder). All except 1 patient died of disease within 4 years. CONCLUSIONS: More than 60% of the patients in the cohort were considered unsuitable for radical cystectomy and their survival was poor, whether treated with full dose radiotherapy or transurethral resection of the bladder alone.

Aged

Cytogenetic analysis of dedifferentiated chondrosarcoma.

Cytogenetic analysis of a dedifferentiated chondrosarcoma with a fibrosarcomatous component revealed the following chromosomal complement: 47,XX,i(1)(q10), add(6)(q13),+7,+8,t(10;12) (p11.2;q11.2),+14,-15,-17, add(19)(q13,4). Chromosome studies of dedifferentiated chondrosarcoma are sparse. Three of the anomalies in the present study are similar to those previously described in dedifferentiated chondrosarcoma.

Chondrosarcoma

Chromosomal anomalies exclusive of telomeric associations in giant cell tumor of bone.

The occurrence of telomeric associations in giant cell tumor of bone is well recognized. However, there has been little emphasis on clonal structural abnormalities that may be seen in addition to or in the absence of telomeric associations. Two cases of giant cell tumor of bone are presented in this study demonstrating clonal karyotypic anomalies other than telomeric association with a review of previously reported cases showing similar findings.

Adult

Effect of indomethacin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced urinary tract carcinogenesis.

The effects of indomethacin on the urinary bladder and renal pelvis in rats treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) were studied. Two hundred female Sprague-Dawley rats were divided into four groups. Group 1 received control diet without added chemicals. Group 2 was treated with indomethacin (1 mg/kg per day) in the drinking water throughout the experiment. Groups 3 and 4 received 0.2% FANFT in the diet for seven weeks followed by control diet. In addition to FANFT, Group 4 received indomethacin, 1 mg/kg per day, for the entire experiment. The rats were sacrificed after 92 weeks. There were no urothelial tumors in the control group, one renal pelvic tumor in the indomethacin group, 4 tumors in the FANFT group and 10 urothelial tumors in the FANFT + indomethacin group. The difference between Groups 3 and 4 was statistically significant (P < 0.05). Moderate and severe hyperplasia of the renal pelvic and papillary epithelium was found in 15 of 48 rats in Group 2 (indomethacin only) as compared with 6 of 49 control rats (P < 0.05). Moderate and severe hyperplasia was equally frequent in Groups 3 and 4 (14 and 17 animals in each group, respectively). Twenty-four rats in Group 2 had mammary tumors as compared to 12 animals in Group 1 (P < 0.01). Five of the tumors in Group 2 were adenocarcinomas. There was no difference between the number of mammary tumors in Groups 3 and 4 (36 and 32 animals in each group, respectively). The results suggest that indomethacin enhances FANFT-induced urinary tract carcinogenesis. Indomethacin also seems to exert some tumorigenic activity in the mammary gland.

Animals

Primary small cell carcinoma of the bladder: a report of 25 cases.

Primary small cell carcinoma of the bladder is a rare condition with approximately 100 cases reported to date. An incidence of 0.7% small cell carcinoma was found in a total series of bladder tumors diagnosed in Western Sweden during a 2-year period. We describe 22 patients with primary small cell carcinoma followed to death or for at least 6 years. Three additional cases were diagnosed at autopsy. Of 18 patients with stages T2M0 to T4M0 cancer treated with locoregional therapy 5 (28%) had no evidence of disease after a median observation of 10 years (range 6 to 18) and 13 died of disease after 0.5 to 19 months (median 7.3). Two patients with metastatic disease were treated with systemic chemotherapy but died within 15 months. Two patients died shortly after the diagnostic biopsy. Our study and a review of the literature indicate that primary small cell carcinoma of the bladder is less aggressive than its pulmonary counterpart and that some patients can be cured by transurethral resection, or partial or radical cystectomy combined with radiotherapy.

Aged

The relationship among multiple recurrences, progression and prognosis of patients with stages Ta and T1 transitional cell cancer of the bladder followed for at least 20 years.

A retrospective study was done on 176 patients with primary stages Ta and T1 bladder cancer treated between 1963 and 1972. One patient was lost to followup after 6 years, while the remainder were followed to death or for at least 20 years. In 1993, 13 patients had no evidence of disease, 39 died of bladder cancer and 123 died of intercurrent disease. Of 77 patients with a primary noninfiltrating tumor and 99 with a primary lamina propria invasive tumor 9 (11%) and 30 (30%), respectively, died of bladder cancer. Recurrences were noted on 10 or more cystoscopic studies in 16 patients and 10 died of bladder cancer 3.5 to 19 years after the primary transurethral resection. A total of 14 patients received repeated thiotepa instillations, all continued to have recurrences and 10 subsequently died of bladder cancer. Only 1 upper tract tumor was diagnosed on routine followup excretory urography. Invasive transitional cell carcinoma of the bladder developed in only 1 of 59 patients who had been tumor-free for 5 years. The results indicate that patients with recurrences on 10 or more cystoscopic studies will continue to have recurrences until death or cystectomy. Recurrence more than 4 years after the primary tumor operation is another ominous sign. Repeated thiotepa instillations did not influence the course of the disease in patients with a history of multiple recurrences. Followup cystoscopy may be discontinued 5 to 10 years after the last recurrence, at least in patients with a solitary low grade primary tumor. Routine followup urographic studies are neither cost-effective, clinically indicated nor justified in patients with superficial bladder cancer.

Carcinoma, Transitional Cell