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Biomedical subjects

S Nordling

Publications and source records attributed to S Nordling.

At least 91 records · Page 5Linked to original sources

Proliferation indices as independent prognostic factors in papillary Ta-T1 transitional cell bladder tumours.

A cohort of 148 patients with papillary Ta-T1 transitional cell carcinomas (TCCs) was followed up for over 10 years and flow cytometric (DNA ploidy, S phase fraction) and morphometric variables (5 nuclear factors, volume corrected mitotic index) were related to prognosis during this period. Recurrence-free survival was significantly related to DNA ploidy, S phase fraction and M/V index. Progression in T-category was predicted by M/V index, S phase fraction, DNA ploidy and WHO grade. The same variables predicted progression in N- and M-categories. In a multivariate analysis only M/V index and S phase fraction were independent predictors of progression. Univariate analysis showed that M/V index, SPF, DNA ploidy and WHO grade predicted survival. In a multivariate survival analysis only M/V index and SPF were independent predictors. The results showed that proliferation indices had independent prognostic value in papillary Ta-T1 TCCs and the grading of these tumours could be based on the proliferation indices. Papillary Ta-T1 tumours with a M/V index value < or = 10/mm2 or SPF < or = 10% had a favourable prognosis whereas tumours with M/V index > 10/mm2 or SPF > 10% had a high malignant potential.

Aged↗

Parenchyma-conserving surgery for renal cell carcinoma.

Between 1969 and 1992, 32 patients underwent conservative surgery (partial nephrectomy or enucleation) for renal cell carcinoma (RCC). Elective parenchyma-conserving surgery (n = 10) was done in patients with small, peripheral kidney tumors and a normal contralateral kidney. Cancer in a solitary kidney, bilateral tumors, dysfunctional contralateral kidney or chronic renal failure were imperative indications (n = 22) for conservative surgery. In the elective group the tumors were 15-100 mm (mean 37 mm) in diameter, in the imperative group 5 to 200 mm (mean 41 mm). The follow-up was 0.2-192 months (mean 48.7 months). Nine of 22 (41%) patients in the imperative group have died of RCC. There were no renal cancer related deaths in the elective group. The 5-year cause-specific survival rates for the elective and imperative groups were 100% and 46%, respectively. Two patients in the elective group have died of unrelated causes. Local recurrences developed in three of 22 patients in the imperative group after a mean of 5.4 years; two of them had von Hippel-Lindau disease with bilateral RCC. Conservative surgery seems to be a feasible option in small peripheral kidney tumors.

Carcinoma, Renal Cell↗

Effect of DNA ploidy classification on prognosis in breast cancer.

A series of 327 breast cancers was analyzed for DNA ploidy by flow cytometry from paraffin-embedded tissue, and the resulting DNA histograms were classified independently by 6 researchers in the field as DNA diploid (Di), aneuploid (An), tetraploid (Te), multiploid (Mu), or technically uninterpretable. The frequency of diploid, aneuploid, tetraploid and multiploid cancers varied from 28 to 41%, 33 to 49%, 8 to 21% and 2 to 6%. According to the scale Di-An-Te-Mu, DNA ploidy was not significantly associated with breast-cancer mortality by 2 classifiers, but if DNA euploid cancers (Di+Te) were tested against non-euploid, or diploid cancers against non-diploid, all classifiers found DNA euploid and diploid cancers to have better prognosis. Mortality associated with diploid or tetraploid cancers decreased with improving histogram quality and increasing uniformity of classification, whereas that associated with aneuploid cancers remained unaltered. Among the cases where all classifiers agreed on ploidy, tetraploid, diploid and aneuploid cancers were associated with 100%, 88% and 68% 5-year survival rates. In this sub-set the S-phase fraction and possibly DNA ploidy were independent prognostic factors, together with histological grade, axillary node status, and primary tumor size.

Breast Neoplasms↗

Evidence that the MCC-APC gene region in 5q21 is not the site for susceptibility to hereditary nonpolyposis colorectal carcinoma.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is the most common form of hereditary colon cancer. Autosomal dominant inheritance is evident from pedigrees but the genetic basis of the disorder is otherwise unknown. Recently, two genes in 5q21 involved in colon carcinogenesis, APC and MCC, were identified, and APC was shown to be the gene predisposing to familial adenomatous polyposis. To determine if these genes also confer susceptibility to HNPCC we performed linkage analyses in nine affected families. The MCC-APC region could be formally excluded as the locus for HNPCC in seven families. In one family the results were suggestive of exclusion, although they were not conclusive. The remaining family was uninformative. We used two alternative definitions of affected status. Based on haplotypes for MCC and APC the added pairwise logarithm-of-odds score for all nine families was -22.57 at the recombination fraction of 0.00 using more stringent criteria for the HNPCC phenotype and -22.67 for less stringent criteria. In addition to blood DNA samples from living family members, DNA from formaldehyde-fixed archival pathology specimens from decreased individuals contributed to these linkage results.

Base Sequence↗

Independent prognostic factors in T2/T3 transitional cell bladder tumours with special reference to histoquantitative methods.

A cohort of 233 T2/T3 transitional cell carcinomas were followed up for over 10 years. Five nuclear factors, two mitotic indices, DNA ploidy and S-phase fraction (SPF) were related to progression and survival of TCCs during that time period. SPF predicted pelvic lymph node involvement at diagnosis (P = 0.064). Progression in T-category was related to T-category (P = 0.035), DNA ploidy (P = 0.0180), papillary status (P = 0.0021), mitotic activity index (MAI) (P = 0.0011), volume corrected mitotic index (M/V index) (P = 0.0017), WHO grade (P = 0.0003) and S-phase fraction (P = 0.0002). Progression in N and M-categories was related to the same variables. Independent predictors of progression in T-category were SPF (P = 0.0161) and WHO grade (P = 0.0236), whereas progression in M-category was independently related to MAI (P = 0.0012) and T-category (P = 0.0004). The SPF (P < 0.0001), M/V index (P < 0.0001), MAI (P < 0.0001), WHO grade (P < 0.0001) and papillary status (P < 0.0001) were the most important predictors of survival in univariate analysis. In a multivariate analysis SPF and M/V index (P < 0.0001) were the best predictors of survival followed by papillary status and T-category. The results show that the proliferation rate of T2/T3 TCCs as determined by flow cytometric SPF or M/V index are equally powerful predictors. They are clearly better than nuclear morphometry, DNA ploidy or WHO grading as prognostic factors.

Aged↗

Significance of variation in DNA flow cytometric analyses from paraffin-embedded breast cancers. Evaluation of the grading efficiency of ploidy determination, DNA index, and S-phase fraction.

116 paraffin-embedded breast cancer samples were analyzed by flow cytometry. From each sample 3 consecutive 50 microns sections were cut for the study. The presence of neoplastic tissue was verified from light microscope sections cut before and after the adjacent sections. One laboratory started with one section from each block and was allowed extra sections when needed for analysis. At the end the laboratory obtained results from all 116 cases. The rest of the samples were studied by 2 other laboratories. Samples with results from 2 or 3 laboratories then allowed variability analysis and the estimation of the grading efficiency in a 2-grade system. Inconsistency in diploidy/aneuploidy distinction was present in 36 of 111 (32.4%) cases studied by two or three laboratories. This inconsistency was less obvious in samples graded as multiploid by at least one of the laboratories. The grading efficiency as analyzed from the results of 3 laboratories was 0.89, and of 2 laboratories, 0.84. The DNA index showed a slightly higher grading efficiency. At the cutoff point of 1.3, 91% of cases could be expected to be correctly classified into low ploidy and high ploidy groups (grading efficiency 0.91). The S-phase fraction had a mean grading efficiency of 0.89, a performance comparable to that of diploidy/aneuploidy distinction. In the light of the available data the flow cytometric analysis can add to the consistency of grading, especially when compared with subjective histological grading. However, the data do not suggest that flow cytometric analysis of paraffin sections as a grading method would be more consistent than quantitative histopathology from sections.

Aneuploidy↗

Healing of bladder wall after contact and non-contact Nd-YAG laser photocoagulation. Experimental study in piglets.

The healing process of the bladder wall after contact and non-contact Nd-YAG laser irradiation was studied in 18 piglets. The animals were sacrificed 1 h, and 2, 5 and 14 days after photocoagulation. The lesions were examined histologically by light and scanning electron microscopy. Immunohistochemical stains were prepared for visualization of lactate dehydrogenase. Perforation of the bladder wall was found in 2 cases where a contact probe was used (15 W/2 s). A crater in the bladder wall resulting from tissue ablation was seen in all cases immediately after contact laser irradiation. Photocoagulation using a non-contact laser led to white necrosis in the bladder wall. Minimal tissue ablation was evident at the highest power setting used (35 W/2 s). After 2 days inflammation around the lesion was marked. Inflammation with fibroblasts invading the damaged area was seen 5 days after photocoagulation. Fourteen days after photocoagulation minor scar formation was evident beneath the histologically normal epithelium. It is concluded that lesions caused by contact or non-contact Nd-YAG laser photocoagulation will heal within 2 weeks with minor scar formation.

Animals↗

DNA ploidy, S-phase fraction, and G2 fraction as prognostic determinants in human pancreatic cancer.

The DNA ploidy, S-phase fraction (SPF), and G2 fraction of pancreatic cancer tissue was measured by flow cytometry in 95 patients. Forty-nine per cent (n = 47) had a diploid DNA index, and 51% (n = 48) of tumours were aneuploid. Aneuploid tumours and high-grade tumours had significantly higher S-phase and G2-fraction values than diploid tumours or low-grade tumours. Diploid and tetraploid tumours had a more favourable prognosis than non-tetraploid aneuploid tumours (p = 0.0020) during the mean follow-up of 6 years. The type of therapy (p = 0.07), histologic grade (p = 0.06), SPF (p = 0.1), and G2 fraction (p = 0.02) had predictive value in survival analysis as well. In multivariate survival analysis, including flow-cytometric, histologic, and clinical variables, diploidy and tetraploidy had independent predictive value. The results suggest that flow cytometry might be used in grading of pancreatic cancer. Such a grading would have practical value if new modes of therapy are being developed. Forty-one per cent of multiple samples had a heterogeneous DNA index when multiple samples were used. Consequently, flow cytometric analysis of pancreatic cancer using multiple samples is recommended.

Adenocarcinoma↗

Vascular changes of pancreatic ducts and vessels in acute necrotizing, and in chronic pancreatitis in humans.

Five patients with severe acute pancreatitis (AP) underwent subtotal pancreatectomy, and six patients with advanced chronic pancreatitis (CP) were subjected to pancreatic resection. Microangiography and histological studies were performed on the resected pancreata. All patients with AP had histologically verified necrotizing pancreatitis. Pancreatic ducts in the necrotic areas had severe inflammation in their walls and a decrease in their vascularity. The ductal walls of CP patients were indistinguishable from the surrounding fibrosis and the vascular supply of the ducts was markedly diminished. The vessels were reduced in number, and their calibers varied considerably. Ductal ischemia in connection with AP and CP is discussed.

Acute Disease↗

Progression and survival in transitional cell bladder cancer: a comparison of established prognostic factors, S-phase fraction and DNA ploidy.

DNA flow cytometric (FCM) data, histological features and clinical stage of bladder tumours in 222 patients were related to outcome during a mean follow-up of 10 years. Aneuploidy was detected in 82 (37%) of tumours and 140 (63%) were diploid. Intratumour heterogenity of DNA ploidy was found in 27% of 30 cases. Aneuploidy and high S-phase fraction (SPF) were related to clinical stage, histological grade and papillarity (P less than 0.0001). Aneuploidy (P less than 0.0001) and high SPF (P less than 0.0001) predicted metastasis to pelvic lymph-nodes and to distant sites. T category (P less than 0.0001), SPF (P less than 0.0001), histological grade (P less than 0.0001), papillarity (P = 0.0021), DNA aneuploidy (P = 0.0094) and G2 fraction (P = 0.0340) predicted cancer-related survival. Multivariate analysis showed DNA aneuploidy as the most important predictor of progression in T category (P = 0.0003) and T category was the most important predictor of lymph-node involvement (P = 0.0083) and metastasis (P = 0.0015), followed by FCM parameters. In Ta-T1 tumours SPF predicted progression independently (P = 0.0153). FCM offers more accurate prognostic information in Ta-T1 tumours than conventional methods. In invasive tumours, FCM offers quantitative prognostic information in terms of pelvic lymph-node metastasis and metastasis to distant sites.

Aged↗

Nucleolar organiser regions (AgNORs) as predictors in transitional cell bladder cancer.

The predictive value of silver stained nucleolar organiser regions (AgNORs) was assessed in 229 patients with transitional cell bladder cancer followed up for over 10 years. The AgNORs were enumerated in pretreatment biopsy specimens. The AgNORs were related to clinical stage (T) (P = 0.0111), papillarity (P less than 0.0001), WHO grade (P less than 0.0001), DNA ploidy (P = 0.0010) and S-phase fraction (P less than 0.0001). Tumours presenting with pelvic lymph node involvement (P = 0.0085) or metastasis (P = 0.0780) at the time of diagnosis had more AgNORs than tumours confined to the bladder wall. Progression in T-, N- and M-categories (P = 0.0010-0.0030) was related to AgNORs and consequently they predicted bladder cancer related survival (P = 0.0005). The diploid tumours could be regrouped according to survival by AgNORs (P = 0.0001). In papillary tumours AgNORs predicted progression (P = 0.0110) and survival (P = 0.0038). In Ta-T1 tumours AgNORs predicted progression (P = 0.11) and survival (P = 0.0751) and also in T2-T3 tumours AgNORs contributed to survival significantly (P = 0.0039). The AgNORs subdivided WHO grade III tumours according to their ability to progress during the follow-up time (P = 0.0711). In a multivariate analysis AgNORs predicted progression independently in Ta-T1 category (P = 0.0165). AgNORs predicted recurrence free period like SPF (P = 0.0010). In conclusion, AgNORs are inferior to classic prognostic factors or DNA flow cytometric variables in muscle invasive bladder cancers whereas they have independent predictive value in superficial cancers.

Carcinoma, Transitional Cell↗

Difference in tissue expression of tumour markers CA 19-9 and CA 50 in hepatocellular carcinoma and cholangiocarcinoma.

The expression of tumour markers CA 19-9 and CA 50, defined by the monoclonal antibodies 1116 NS 19-9 (19-9 antibody) and C 50, was studied by the immunoperoxidase technique in formalin-fixed, paraffin-embedded tissue sections from 11 hepatocellular carcinomas and 10 cholangiocarcinomas of the liver, and from specimens of normal liver and liver cirrhosis. The 19-9 and C 50 antibodies react with sialosylfucosyllactotetraose, corresponding to sialylated blood group antigen Lewis, and the C 50 antibody also with another sugar moiety, sialosyllactotetraose. Neither marker was cancer specific. The CA 19-9 and CA 50 antigens are normal constituents of bile ducts. Nine out of 10 cholangiocarcinomas stained for CA 50, and eight out of 10 for CA 19-9. There was no apparent difference between the staining pattern of CA 19-9 and CA 50. Hepatocellular carcinomas were consistently negative for both markers. Thus, hepatocellular carcinomas and cholangiocarcinomas showed a clear difference in the reactivity for tumour marker antigens CA 19-9 and CA 50. This difference might be of clinical importance in the differential diagnosis between hepatocellular carcinoma and cholangiocarcinoma.

Adenoma, Bile Duct↗

Relationship between DNA ploidy and survival in patients with exocrine pancreatic cancer.

The DNA ploidy of pancreatic cancer tissue from paraffin blocks was measured by flow cytometry in 46 patients whose disease had been detected and treated with surgery. Lymph node involvement was observed at the time of diagnosis in 36% of patients with diploid tumors and in 79% of patients with aneuploid tumors (p = 0.017), but no clear relation to metastasis could be observed (p = 0.201). The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumors (p = 0.007). All patients who underwent radical surgery had diploid DNA content and SPF below the median (11.5%). Seven patients with a diploid tumor (32%) and none of the aneuploid cases survived 1 year. Over the 1-year period, in order of importance, the type of treatment (p less than 0.001), DNA ploidy (p = 0.004), tumor size (p = 0.0046), and lymph node status (p = 0.027) predicted survival. Aneuploidy showed a significant association with decreased cumulative survival (p = 0.015), and a suggestive relationship with SPF was found. The results suggest that DNA ploidy of pancreatic cancer can be used in dividing the patients into different prognostic groups. The value of the detection of aneuploidy, however, is limited, because diploid pancreatic cancers are also generally rapidly fatal.

Adult↗

Renal function after partial nephrectomy with the Nd-YAG laser. Experimental study in piglets.

Twelve partial nephrectomies were performed in 12 piglets using either the combination (contact and non-contact) Nd:YAG laser technique or a steel scalpel. Additional haemostasis was attempted with ligatures. The renal artery was not clamped and renal cooling was not attempted. Total nephrectomy was performed on the contralateral side. Serum creatinine and urea levels were measured, and 99mTc-DTPA renography was performed pre-operatively and 1 and 2 weeks post-operatively. One week post-operatively the mean serum creatinine level was 35% higher than the pre-operative level in the laser group and 30% higher in the steel scalpel group. Two weeks post-operatively the respective differences were 34 and 24%. The mean urea level 1 week after operation was 50% higher than the pre-operative level in the laser group and 17% higher in the steel scalpel group. Two weeks post-operatively the respective differences were 38% in the laser group and 20% in the steel scalpel group. The mean DTPA disappearance rate was 34% lower 1 week after operation in the laser group and 23% lower in the steel scalpel group when compared with the preoperative state. Two weeks post-operatively the respective changes were 48 and 25%. These data indicate that there is no significant difference in renal function when the Nd: YAG combination laser technique is used in partial nephrectomy as compared with the steel scapel.

Animals↗

DNA ploidy, S phase fraction and G2 fraction as prognostic determinants in prostatic adenocarcinoma.

The results of DNA flow cytometry (FCM), histological features and clinical stage of prostatic adenocarcinoma were correlated to outcome in 91 patients during a mean follow-up period of 15.6 years. Aneuploidy was detected in 33 (36%) tumours, and 59 (64%) tumours were diploid. Eighteen (20%) tumours showed a tetraploid DNA index. The frequency of tetraploidy increased towards high-stage and high-grade tumours. Aneuploidy, high S phase fraction (SPF) and G2 fraction were significantly related to clinical stage, histological grade and perineural infiltration. Progressing tumours (T category) had higher SPF values (p = 0.0248), and progression in N (p = 0.0122) and M categories (p = 0.0021) was related to high G2 fraction as well. In T1-2 tumours, DNA ploidy (p = 0.0280) and SPF (p = 0.0230) predicted progression, whereas histological grade had no significant predictive value. The clinical stage (T) predicted crude survival (p = 0.0005). Results show that FCM gives prognostic information in prostatic adenocarcinoma beyond that of histological grading.

Adenocarcinoma↗

Intratumoral heterogeneity of DNA indexes in transitional cell bladder cancer: relation to tumor histology.

DNA flow cytometry (FCM) was performed from multiple samples in 60 transitional cell bladder carcinomas (TCC) to detect intratumoral heterogeneity of DNA index (DI). The samples for analysis were selected randomly and they were paraffin-embedded peroperative biopsy specimens from the primary TCCs. Intratumoral heterogeneity of DI was found in 12 of 60 (20%) samples. All WHO grade I tumors were diploid whereas 12 of 41 (29%) WHO grade II-III tumors showed a heterogeneous DI. DI heterogeneity was related to WHO grade (p = 0.004), mitotic frequency (p = 0.002), inflammatory cell infiltration (ICI; p = 0.003) and nonpapillar growth pattern (p = 0.06). In multivariate analysis, the WHO grade (p = 0.027) and the degree of ICI (p = 0.041) were independently related to heterogeneous DI. The results show that (a) many of the WHO grade II-III TCCs are composed of diploid and aneuploid cell populations; (b) the presence of dense ICI and TCCs may lead to false diploid DI. Consequently, the analysis of multiple samples is recommended in WHO grade II-III tumors to detect aneuploidy particularly when dense ICIs are present.

Aneuploidy↗

Relationship between DNA flow cytometric data, nuclear morphometric variables and volume-corrected mitotic index in transitional cell bladder tumors.

The relationship between the mean nuclear area, standard deviation of the nuclear area, the mean area of the 10 largest nuclei in a section (NA10), volume-corrected mitotic index (M/V index), DNA index (DI) and S-phase fraction (SPF) were assessed in a panel of 222 transitional cell bladder tumors. The relations between the morphometric variables and DI (p less than 0.0001), and between the morphometric variables and SPF (p less than 0.0001) were highly significant. Pearson's correlation coefficients between NA10 and DI (r = 0.413) and between SPF and the M/V index (r = 0.536) were also highly significant (p less than 0.0001). The SPF could be estimated reliably by morphometric methods, whereas the estimation of DI is not perfect. The combination of morphometric variables allowed a more reliable estimation of flow cytometric parameters. The results suggest that DI and SPF can be semiquantitatively estimated in routine histopathological sections by simple morphometric methods.

Carcinoma, Transitional Cell↗

Serum carcinoembryonic antigen and DNA ploidy in colorectal carcinoma. A prospective study.

We have analysed the relationship between carcinoembryonic antigen (CEA) and DNA ploidy prospectively in 130 colorectal carcinoma patients. CEA was elevated preoperatively significantly more often in patients with DNA-aneuploid tumours than in DNA-diploid or DNA-tetraploid tumours--that is, in 48% (36 of 75) of patients with aneuploid tumours, in 34% (14 of 41) of patients with diploid tumours, but only in 14% (2 of 14) of patients with tetraploid tumours (p less than 0.05). Aneuploid tumours had an elevated CEA level in 38% of stage A-B disease and in 61% of stage C-D disease. The elevated CEA values (greater than or equal to 5.0 micrograms/l) correlated with tumour stage in patients with aneuploid tumours but not in patients with diploid tumours. Whereas CEA is a suitable marker for aneuploid carcinomas, other more sensitive tumour markers should be sought for diploid and also for tetraploid tumours. If such markers are found, flow cytometry could provide the most important information in selecting individual follow-up programmes for colorectal cancer patients.

Adult↗