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Progesterone-binding cyst protein (PBCP = GCDFP-24) and steroid hormone receptors as markers of differentiation in breast cancer. Inverse relation of distribution in normal and malignant tissue of the same breast.

Progesterone-binding cyst protein (PBCP, identical to Gross Cystic Disease Fluid Protein; GCDFP-24) has been evaluated as a possible marker of differentiation in breast tissues. In 17 women with verified operable breast cancer, we have quantitated the cytosol content of PBCP, steroid hormone receptors (estrogen receptor[ER], progesterone receptor[PR] and androgen receptor[AR] as well as albumin in specimens from the primary tumor and from the adjacent non-malignant tissue of the same breast. A significantly higher amount of PBCP (p less than 0.001) and albumin (p less than 0.003) was found in the non-malignant tissue. Conversely, the content of steroid receptors was significantly higher (p less than 0.001) in the malignant tumor, compared to the non-malignant breast tissue. A significant correlation (p = 0.005) between PBCP content in the malignant tumor and in the non-malignant tissue was found. In malignant tissue, ER was significantly correlated with AR (p = 0.007) and to age at operation (p = 0.006). Our results are in agreement with recent reports on other tissue parameters, which indicate qualitative and quantitative differences between the malignant and the non-malignant counterpart with regard to regulation of cell growth and the expression of differentiation markers. This study provides evidence for PBCP as a marker of differentiation to be implemented in further clinical and basic research on breast cancer.

Apolipoproteins↗

[Study of parameters to evaluate the grade of malignancy of colorectal cancer with submucosal invasion].

Histological sections were prepared from 69 cases of colorectal cancer and the following 3 parameters were determined: A) the area of malignant change (mm2), B) the area of malignancy in the submucosal layer (mm2), and C) the proportion of B to A (%). The relationship between these parameters and biological malignant findings (lymph node metastasis and lymphatic and/or venous invasion) was investigated. There was no relationship between A and biological malignant findings. Lesions with B values of less than 7.5 mm2 were not associated with biological malignant findings but those with values more than 30 mm2 always were. A significant difference in B values was noted between patients with and without these findings (22.0 +/- 13.2 mm2 vs. 6.5 +/- 7.0 mm2, p less than 0.01). C values of more than 45% were always associated with biological malignant findings but values less than 20% never were. A significant difference in C values was observed between patients with and without these findings (57.6 +/- 22.1% vs. 14.1 +/- 11.3%, p less than 0.01). These results suggested that the area of malignancy in the submucosal layer and its percentage to the entire area of malignant change on the histological sections were useful parameters to evaluate the grade of malignancy of invasive colorectal carcinoma.

Colorectal Neoplasms↗

Malignant colorectal strictures in Crohn's disease.

One hundred thirty-two of 980 patients (13.5%) with Crohn's disease (CD) involving the colon, admitted to The Mount Sinai Hospital between 1959 and 1985, developed 175 colonic strictures. Thirty-three patients developed more than one stricture. The frequency was twice as great in colitis (19%) as in ileocolitis (11%). Ten malignant strictures were identified in nine patients (three ileocolitis, six colitis). One of these patients had three strictures (two malignant, and one benign), and two had two strictures (one malignant and one benign). The frequency of cancer in patients with stricture (6.8%) was higher than in those without stricture (0.7%, six of 848, p less than 0.001). There were no differences in clinical symptoms between patients with benign and malignant stricture. Seventeen of 165 benign strictures (10.3%) were long, extending over more than one anatomical segment of colon, but all 10 malignant strictures were short (p less than 0.0001). The age at the diagnosis of stricture was higher in the nine patients with malignant stricture than in the 123 patients with benign stricture (mean age 57.2 vs. 41.4 yr, respectively, p less than 0.01). The proportion of strictures that were malignant increased with duration of disease from 3.3% with less than 20 yr of CD, to 11% with CD of 20 yr or more. All nine patients with malignant stricture were treated surgically, and four of the nine died of colon cancer during a mean follow-up of 4.3 yr. Prognosis was worse in six other nonstricture cancers in this series, with five colon cancer deaths during mean follow-up of 1.6 yr. In view of the high rate of malignancy, 6.8% in this series, colonoscopy with biopsy is essential in Crohn's disease patients with colonic strictures, and surgery must be considered when a stricture cannot be fully assessed during colonoscopy.

Adolescent↗

Mucinous cystic neoplasm of the pancreas. Estimation of grade of malignancy with imaging techniques and its surgical implications.

The results of diagnostic imaging procedures, macroscopic and microscopic findings and clinical follow up data of 20 mucinous cystic neoplasms of the pancreas were retrospectively reviewed to determine the grade of malignancy and its surgical implications. The largest mean diameter was 8.9 cm for 10 malignant cases, 5.0 cm for two premalignant cases, and 3.1 cm for eight benign tumours. Ultrasonography or computed tomography or both, corresponded well with macroscopy. The 10 malignant and two premalignant lesions had intracystic mural nodules or extracystic solid components, while the eight benign specimens had neither nodules nor solid portions. Structural complexity seen on ultrasonography or computed tomography, which reflected the irregularity in size and shape of the cysts, internal septa, walls, and solid components, was severe in the 10 malignant and two borderline tumours and mild or moderate in the eight benign lesions. Angiography showed that five of the nine malignant tumours were hypervascular, while the two premalignant and four benign lesions were all avascular. Five of 10 patients with malignant tumours died of local recurrence or remote hematogenous metastases, and one with malignant disease was still alive with liver metastases at the time of writing. We propose that a careful preoperative estimate of the malignant potential of such cysts should be made based on the size of the tumour, the presence of mural nodules and solid areas, and the structural complexity on ultrasonography or computed tomography, as well as the amount of vascularity seen on angiography. Attention should be paid at follow up to the presence of local recurrence and haematogenous metastases in cases of malignant disease.

Adenocarcinoma, Mucinous↗

Malignant transformation of human fibroblasts by oncogene transfection or carcinogen treatment.

Exposure to chemical carcinogens or radiation is considered to cause most human cancer, but human cells in culture have not been successfully transformed to malignancy by such agents. Malignant transformation is a multi-step process and one explanation for the failure to induce such transformation of human cells in culture could be inability to recognize the phenotypes of carcinogen-treated cells that have undergone intermediate changes, so that these cells can be isolated and exposed a second time to cause further changes. To identify possible intermediates, we transfected diploid human fibroblasts with oncogenes known to be active in cells derived from fibrosarcomas and determined the phenotypes produced. H- or N-ras oncogenes flanked by suitable enhancer and promoter sequences caused the cells to exhibit several characteristics of malignant cells, but not to acquire an infinite life span or form tumors. Transfection of these oncogenes in the same constructions, or a viral K-ras oncogene, into an infinite life span, near-diploid, non-tumorigenic cell strain developed in this laboratory (MSU-1.1 cells) resulted in distinct foci of morphologically-altered, anchorage independent, and growth factor independent cells that formed progressively-growing, invasive malignant sarcomas in athymic mice and expressed the p21s of the transfected ras genes. Transfection of two other infinite life span human cell lines with the H-ras oncogene in the same construction also yielded malignant cells. Recently, we succeeded in inducing the malignant state in MSU-1.1 cells using carcinogen identified that are one step removed from malignant transformation, others that are two-steps removed, etc. Furthermore, we know what new phenotypes these cells need to express to be malignantly transformed and which oncogenes can make such a change. If, as suggested above, proto-oncogenes are the cellular targets for carcinogen attack, it should be possible, by carcinogen treatment to bring about the malignant state. We have recently succeeded in achieving just such transformation by exposing MSU-1.1 cells to chemical carcinogens.

Animals↗

[A mathematical model of age distribution of malignant tumours mortality].

There was a tendency that the mortality of malignant tumours increased with age. In order to explore the law of this tendency, the data of malignant tumours mortality from disease monitoring points in Shandong Province were mathematically analogized, and the mathematical model of age distribution of malignant tumours mortality was established by using the exponential curve, y = 10a + bx. The model was also tested and verified by using national data, to observe the universal significance of the model. The model gave a theoretical account of the law of age distribution of malignant tumours mortality from a population, and provided an initial method to predict malignant tumours mortality. The increment quantity of malignant tumours mortality in various age groups when age increased one year could be calculated by using the differential equation from the exponential curve equation, y = 10a + bx. Further, "an increment multiple constant" of the increment quantity of malignant tumours mortality could be calculated. The constant could be used as an Index for comparison in risk degree and age distribution law of malignant tumours mortality among various age groups and the same age group in different periods, and provided leads for further research of the causes of malignant tumours.

Age Factors↗

Activity of the human blood group ABO, Se, H, Le, and X gene-encoded glycosyltransferases in normal and malignant bladder urothelium.

Immunohistochemistry has led to the finding of an expression of ABO-related blood group antigens in normal and malignant bladder urothelium which is different from that found on erythrocytes from the same individual. This includes a loss of blood group ABO expression in malignant urothelium, and the expression of Leb antigens in normal and malignant cells from individuals with Le(a+b-) and Le(a-b-) erythrocytes. To elucidate the mechanism of this blood group antigen expression in urothelium we have analyzed the activity of the specific glycosyltransferases encoded by the ABO, Se, H, Le, and X blood group genes in normal and malignant urothelium. Biopsies of normal urothelium were obtained from 22 individuals and biopsies of urothelial tumors from 20 individuals. The tissue donors were typed for ABO, Lewis, and secretor status on erythrocytes and saliva. The biopsies were disaggregated to single cell suspensions, and the activity of the individual glycosyltransferases was determined as pmol of labeled sugar incorporated by oligosaccharide acceptors per 100,000 cells. The A (alpha-3-N-acetyl-D-galactosaminyl) and B (alpha-3-D-galactosyl) gene-specified transferases showed no activity in malignant cells, whereas all other enzymes examined were expressed in both normal and malignant cells. Secretors and nonsecretors showed the same alpha-2-L-fucosyltransferase activity in both normal and malignant cells, whereas the alpha-3-L-fucosyltransferase was reduced (P less than 0.02) in malignant cells from Lewis positive individuals. The Lewis gene-encoded alpha-4-L-fucosyltransferase showed a similar activity in Lewis positive and negative individuals. These results indicate that the disappearance of A and B blood group antigens in bladder tumors and the expression of Leb antigens in normal and malignant cells from individuals with Le(a+b-) and Le(a-b-) erythrocytes are due to corresponding differences in glycosyltransferases. The results indicate that the ABO, H, Se, and Le genes are subjected to a tissue-dependent differential expression.

ABO Blood-Group System↗

[Non-Hodgkin's lymphomas of low-grade malignancy with particular reference to the lymphocytic lymphomas of B-cell origin (author's transl)].

More than two thirds of all non-Hodgkin's lymphomas (NHL) are of low-grade malignancy. This group comprehends five histological types: lymphocytic, immunocytic, plasmacytic, centrocytic, and centroblastic-centrocytic lymphomas. The lymphocytic lymphomas are second in frequency among the biopsies. The most common lymphocytic lymphoma is the chronic lymphocytic leukemia (CLL). It is characterized by the proliferation of small lymphocytes. The quantity and arrangement of the constantly present paraimmunoblasts and prolymphocytes allow to distinguish three histological subtypes of CLL. CLL, prolymphocytic leukemia, and hairy cell leukemia may be composed of B- or T-cells. Mycosis fungoides, Sézary's syndrome and T-zone lymphomas are T-cell lymphomas. All NHL of low-grade malignancy show a proliferation of small to medium sized lymphoid cells. Some large blast forms may be intermingled among these smaller cells. The inhomogeneity of low-grade malignant lymphomas with regard to the size of predominant cells and the admixture of blast forms determine the higher ("intermediate") degree of malignancy of some types in the group of low-grade malignant lymphomas. The overgrowth of the intermingled blast forms probably leads to the transformation into a lymphoma of high-grade malignancy. This event happens in variable frequency in the various types of low-grade malignant lymphomas. NHL of low-grade malignancy occur almost exclusively in adults, whereas the high-grade malignant lymphomas are found in all age-groups.

Adolescent↗

[Cutaneous-internal malignancy syndrome associated with specific skin lesions].

Skin changes associated with internal malignancies can be classified into five groups: 1) cutaneous metastasis from internal malignancies, 2) non-specific reactional skin changes caused by toxic or allergic processes due to these malignancies, including pruritus cutaneous, urticaria and so on, 3) specific skin changes or diseases closely related to the malignancies, including acanthosis nigricans, dermatomyositis, Leser- Trélat syndrome, 4) the syndrome caused by simultaneous effects of oncogenesis both on the skin and on the internal organs, including multiple Bowen's disease, and 5) congenital hereditary syndrome, including Gardner syndrome, Torre syndrome. It is appropriate for the cutaneous internal malignancy syndrome to include above groups 3) 4) 5), because of the close and specific interrelation between the skin changes and internal malignancies. Two cases of glucagonoma syndrome, 2 cases of dermatomyositis with malignancy and one case of Leser- Trélat syndrome were described as typical cutaneous-internal malignancy syndrome. Characteristics findings of these skin changes suggest the presence of particular internal malignancies in cases, and the study of the etiologic process of these skin changes will be useful in the basic oncological investigation.

Adult↗

Anti-ATLA (antibody to adult T-cell leukemia virus-associated antigen), highly positive in OKT4-positive mature T-cell malignancies.

Serum or plasma specimens from 252 patients with lymphoid malignancies were screened for reactivity with adult T-cell leukemia virus-associated antigen (ATLA), and the relationship between the immunologic phenotype of the tumor cells and ATLA reactivity was determined. Anti-ATLA antibodies were found in 24 (29.3%) of 82 patients with T-cell malignancy. In contrast, the antibodies were found in none of the 106 patients with B-cell malignancy and only rarely in patients with other lymphoid malignancies without blood transfusions. Among the patients with T-cell malignancy, anti-ATLA antibodies were found in 23 (45.1%) of the 51 patients with OKT4-positive mature T-cell (inducer/helper T-cell) malignancy, but in none of the patients with T-cell malignancy of pre-T, thymic T-cell or OKT8-positive mature T-cell (suppressor/cytotoxic T-cell) phenotype. Furthermore, among the OKT4-positive mature T-cell malignancies, the antibodies were found in 16 (84.2%) of 19 patients with ATL and in 5 (27.8%) of 18 patients with mature (peripheral) T-cell lymphoma, in none of four with typical T-chronic lymphocytic leukemia, in one of nine with mycosis fungoides and in the one patient with small-cell variant of Sézary's syndrome. These results suggest that anti-ATLA positive T-cell malignancies with OKT4-positive mature T-cell phenotype must be the same disease, because it is highly possible that they have the same etiology and the same cellular origin. In the atypical cases, it seems necessary to demonstrate monoclonal integration of proviral DNA of ATLV or HTLV into the tumor cells in order to establish the final diagnosis of ATL.

Antibodies, Viral↗

Malignant mammary tumors in beagle dogs dosed with investigational oral contraceptive steroids.

Of 172 beagle dogs administered investigational oral contraceptive steroids for 2.4-5.2 years, 9 developed malignant mammary tumors. At necropsy their ages varied from 41 to 70 months, with a mean age of 4.9 years. The malignant tumors were observed in 1 dog that received ethynerone plus mestranol at 1.05 mg/kg/day and in 4 dogs that received chlorethynyl norgestrel plus mestranol at 1.05 mg/kg/day. Also, 4 dogs that received anagestone acetate plus mestranol at either 0.44 or 1.10 mg/kg/day developed malignant mammary tumors. Malignant tumors were not seen in 33 dogs administered mestranol at 0.02 and 0.05 mg/kg/day for 7 years or in 18 dogs given ethynerone without mestranol at 1.00 mg/kg/day for 5 years. No malignant tumors were observed in 18 control dogs maintained for 7 years without treatment. Three dogs had single malignant mammary nodules, 3 dogs had 2 malignant nodules, 2 dogs had 4-6 malignant nodules, and 1 dog in the treatment group given high dosages of ethynerone plus mestranol had 14 mammary nodules composed of fibrosarcoma. The malignant tumors were histologically classified as 5 anaplastic carcinomas, 2 solid carcinomas, 1 tubular adenocarcinoma, 1 squamous cell carcinoma, and 1 fibrosarcoma. Most dogs had only 1 histologic type of cancer (8/9 dogs); however, 1 dog had carcinomas of both solid and anaplastic types involving different glands. Metastases were present in 5 dogs and most often involved regional lymph nodes and lung.

Adenocarcinoma↗

Colour and pulsed Doppler US and tumour marker CA 125 in differentiation between benign and malignant ovarian masses.

BACKGROUND: Colour and pulsed Doppler flow imaging have been proposed as methods that may be useful in differentiating benign from malignant ovarian masses. It was hypothesised that the detection of neovascularisation with abnormal, low-resistance blood flow peculiar to malignant tumours is possible, which is characterised with angle-independent Doppler indices Pl and Rl (pulsatility and resistance index, respectively). Tumour marker CA 125 SC (serum concentration) was found to be elevated in 80-85% of patients with serous epithelial ovarian cancer and in a lower percentage in other ovarian cancers, with levels over 35U/ml suggestive of malignancy. In our study we wanted to determine whether colour and pulsed Doppler US and CA 125 SC can be used to differentiate benign from malignant ovarian masses and whether, by combining the methods, the results can be even improved. METHODS: Ovarian masses identified by sonography in 71 patients aged 35 years or more were confirmed at surgery (n = 61) or endoscopy (n = 4) or followed up to resolution with US (n = 6). Colour and pulsed Doppler US were used to identify intratumoral areas of vascularisation and to calculate the lowest Pl and Rl for each ovarian mass. CA 125 SC were measured. RESULTS: In 16 of 18 ovarian malignancies and 28 of 53 benign masses, areas of intratumoral vascularisation were detected with colour Doppler US (p = 0.002). Pl and Rl values displayed considerable overlap between malignant and benign lesions and the differences were not significant. Mean CA 125 SC was higher in malignant than in benign masses (p = < 0.0001). For cut-off at 35U/ml, sensitivity (SE), specificity (SP), positive predictive value (PPV) and negative predictive value (NPV) for ovarian cancer were 83%, 74%, 79% and 75% respectively. Either CA 125 SC > 35U/ml or intratumoral colour Doppler signal was detected in all 18 patients with ovarian cancer, but neither of them was detected in 25 patients all of whom had benign tumours. Thus, combining the two methods, SE, SP, PPV and NPV for ovarian cancer were: 100%, 47%, 32% and 100% respectively. CONCLUSIONS: RI and PI values thus cannot be used to differentiate between benign and malignant ovarian tumours. The determination of CA 125 serum level is useful in identifying ovarian cancer. CA 125 SC under 35U/ml, together with the lack of detectable colour flow in the tumour, can reliably exclude ovarian malignancy (NPV = 100%).

Adult↗

[De novo malignancy following renal transplantation].

The characteristics and incidence of de novo malignancy was analyzed in 376 renal transplant recipients transplanted between April 1970 and December 1992. Malignancies developed in 21 recipients of living related donor renal allografts. The total number of malignancies was 23, with 2 patients developing 2 malignancies. The mean age at the time of diagnosis was 42 years. The average interval from transplantation to the time of diagnosis was 129 months. Malignancy developed in 12 of 21 patients who survived 10 years with a functioning graft. Nine patients died of their malignancy. The risk of developing malignancy is increased following renal transplantation. Compared with sex- and age-matched Japanese control, the incidence is 6.1 times greater for male, 10.5 times greater for female, and 7.3 times greater overall. The risk was increased at all sites except the stomach. The risk rate of acquiring malignancies at 5-year intervals following transplantation was 6.5 times greater from 0 to 5 years, 10.0 times greater from 5 to 10 years, and 9.3 times greater from 10 to 15 years. These results suggest that annual medical examinations should be performed as part of the routine log-term follow-up of renal transplant recipients to detect malignancies in the early stage.

Adult↗

[Differentiation of benign and malignant ovarian tumors by transluminal ultrasound scanning].

We intended to evaluate ultrasonographic criteria for differentiation of benign and malignant ovarian tumours, and to estimate the risk of malignancy in unilocular ovarian cysts. The files of 186 women aged 40 or above, who had undergone surgery in the department of gynaecology and obstetrics at Hillerød hospital between 01.01.1988-31.12.1990 and where pathological ovarian histology was found were reviewed. Preoperative ultrasonographic examination concerning size and morphology was compared to histological diagnosis. Tumours were classified according to the ultrasonographic internal structure into a) unilocular cysts, b) unilocular cysts with solid areas, c) multilocular cysts, d) multilocular cysts with solid areas and e) solid tumours. Criteria for suspicion of malignancy were unilocular cysts > 10 cm and complex and solid tumours, whereas smaller unilocular cysts were thought to be benign. Twenty-one tumours, diagnosed by ultrasound as unilocular cysts were all histologically benign, independently of size. For complex and solid tumors there was an increased risk of malignancy, and a statistically significant correlation between tumour size and risk of malignancy was found. Using the ultrasonographic criteria for malignancy a sensitivity of 97% and a specificity of 28% was found. The suggested criteria for ultrasonographic suspicion of malignancy were found usable in differentiating benign and malignant ovarian tumours. The risk of malignancy for unilocular cysts seems to be low, independently of size.

Adult↗

Factors contributing to the accuracy in diagnosing ovarian malignancy by color Doppler ultrasound.

OBJECTIVE: To determine whether resistance index values obtained by color Doppler ultrasound contribute to the accuracy in diagnosing ovarian malignancies. METHODS: Four hundred ten patients with ovarian neoplasms referred for color Doppler ultrasound evaluation were enrolled, excluding patients examined during the luteal phase. Resistance index of the intra-tumor arteries was measured by color Doppler ultrasound. The corresponding clinical and histopathologic information was recorded. For statistical determinations, we used the Yates corrected chi 2 analysis, Fisher exact test, Student t test, and linear regression analysis. RESULTS: Satisfactory intra-tumor artery waveforms were obtained in 96.1% (99 of 103) of ovarian malignancies. Resistance index values varied at 0.23-0.82. Regression analysis of resistance index values on tumor size and amount of ascites demonstrated a linear association (R = 0.498 and 0.362, respectively; P < .01 in both). If we regard a resistance index of 0.4 as a cutoff value, the overall sensitivity and specificity in detecting malignancy were 68.0 and 97.4%, respectively. Primary ovarian malignancies exhibited significantly more false negatives (30 of 79) than malignancies metastasized to the ovary (three of 24) (P = .018). Malignancies containing mainly cystic components exhibited more false negatives (20 of 41) than did tumors with primarily solid components (13 of 62) (P < .01). Significantly more false negatives were encountered in malignancies with larger diameters (greater than 10 cm) compared to smaller ones (27 of 63 versus six of 40; P < .01), and in malignancies accompanied by considerable ascites (greater than 1000 mL) (13 of 25 versus 20 of 78; P < .05). CONCLUSIONS: Tumor origin, size, component nature, and amount of ascites contributed to the accuracy in diagnosing ovarian malignancies using resistance index values obtained by color Doppler ultrasound.

Adolescent↗

Differentiation of purified malignant B cells induced by PMA or by activated normal T cells.

We studied the in vitro differentiation (immunoglobulin production) of purified malignant B cells of 21 patients with different B-cell malignancies, including chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) and non-Hodgkin lymphoma (NHL). Direct activation of purified malignant B cells with phorbol myristate acetate (PMA) resulted in the differentiation of most CLL cells, but not of the other types of B-cell malignancies. This differentiation required the presence of interleukin 4 (IL-4). In contrast, with the use of anti-CD2-stimulated normal T cells and IL-2, immunoglobulin M (IgM) could be detected in the supernatant of all but one of the purified malignant B-cell populations. However, by analysis of the light chains of the IgM produced, monoclonality could be demonstrated in only 13/21 cases: 8/11 CLL, 3/3 PLL, 0/3 HCL, and 2/4 NHL. In two patients additional proof that the malignant B cells were the source of the IgM production could be obtained in an idiotype-specific ELISA. Apart from IgM, also the production of IgG antibodies could be detected. However, only for 2/3 HCL patients, we could confirm a monoclonal IgG production. Since HCL is a malignancy of mature B cells, already carrying IgG on the membrane, this IgG production is not the result of a switch process. In all other cases where IgG production was polyclonal, we have no indications for the induction of Ig switch. The fact that the more mature B-cell malignancies were T-cell-dependent for their differentiation might be a reflection of the in-vivo situation. The efficient induction of malignant B-cell differentiation described in this paper allows investigation of the antigen specificity of these antibodies.

Antibodies, Anti-Idiotypic↗

Malignant disease appearing late after operation for T1 N0 non-small-cell lung cancer. The Lung Cancer Study Group.

Occurrences of malignancy in 308 patients who were clinically free of cancer 60 months or more after surgical treatment of T1 N0 non-small-cell lung cancer are summarized. At last report, 210 patients remained alive with no evidence of malignant disease, 43 patients died of nonmalignant causes, and 55 patients had 59 occurrences of malignant disease. Late lung cancer recurrence was observed in 22 patients (concurrent with nasopharyngeal cancer in one patient and with laryngeal cancer in one patient). Metachronous second lung cancer was noted in 20 patients (including concurrent colon cancer in one patient and metastatic recurrence in one patient). Other nonpulmonary malignant tumors appeared in 13 patients. Including second lung cancer, 25 cancers of aerodigestive epithelium were observed in 23 patients. The malignancy-free survival advantage for patients with squamous cancer observed until 60 months after resection was not sustained at 60 months and beyond. At the time of last follow-up, 84 patients (27%) had died; 43 were free of malignancy, and 41 had malignancy (14 patients were alive with malignancy and 210 with no evidence of disease). These data reinforce two conclusions: (1) The probability of lung cancer recurrence or appearance of new lung cancer 5 years or more after successful operation in this select subpopulation of patients with lung cancer is of concern. (2) The malignancy-free survival advantage of patients with squamous cancer disappears after 5 years.

Adult↗

Flow characteristics in benign and malignant gynecologic tumors using transvaginal color flow Doppler.

OBJECTIVE: To assess flow characteristics of benign and malignant gynecologic tumors by transvaginal color flow Doppler. METHODS: Records of the Ultrasound Laboratory, Women's Cancer Center, University of Minnesota were analyzed retrospectively. Gray scale findings were recorded as either "diagnostic" or "nondiagnostic." Color flow assessment was performed on intratumor vessels or ovarian and/or uterine arteries. Flow was recorded as either "absent" or "present." Spectral analysis allowed determination of the systolic, diastolic, and mean velocities and calculation of the pulsatility and resistance indices. Malignancy was then predicted based upon color flow findings alone, with malignant tumors demonstrating increased color flow and a pulsatility index of at most 1.0 or a resistance index of at most 0.4. Color flow Doppler findings were then recorded as "giving additional useful information" that either confirmed questionable gray scale findings or changed the gray scale sonographic diagnosis, or as "not giving additional information" over the gray scale diagnosis. RESULTS: Two hundred thirty-one patients had gray scale sonography, and 167 also had color flow Doppler performed. Gray scale sonographic findings were sufficient to make a diagnosis in 156 (93%) of the scans. Color flow Doppler findings added useful information in 49 scans (30%). Increased color flow was highly significant (P < .0001), as was the calculated pulsatility index (P < .02) and resistance index (P < .008), in distinguishing benign from malignant tumors. Ovarian and uterine artery and intratumor assessments of the systolic, diastolic, and mean velocities were not significantly different between the benign and malignant tumors. Regression analysis confirmed the presence or absence of color flow as an independent predictor of malignancy or benignity (P < .0001). CONCLUSIONS: Our large study confirms the overall accuracy of gray scale scanning. When used alone, color flow Doppler--although specific--lacks sensitivity and predictive value as an independent predictor of malignancy. When findings were combined with those obtained from gray scale scanning, sensitivity, specificity, and predictive value were improved to acceptable levels. Significant differences existed between benign and malignant tumors for calculated pulsatility index and resistance index, but neither was sufficiently sensitive, specific, or predictive to be used alone as sole criteria of malignancy prediction. Other flow indices studied (systolic, diastolic, and mean velocities) in general did not differ significantly between groups. Physicians should be cautioned against using color flow findings alone for clinical decision making. We recommend a multi-institutional study to investigate the multiple vascular assessments to determine the role of color flow Doppler in the preoperative prediction of pelvic tumors and in screening for gynecologic abnormality.

Adult↗