Gain of 17q in malignant fibrous histiocytoma is associated with a longer disease-free survival and a low risk of developing distant metastasis.

In this study, a panel of 39 primary malignant fibrous histiocytomas (MFH) of high malignancy grade were characterised for chromosomal alterations. The results were then evaluated in relation to the survival and the occurrence of recurrent disease during follow-up for an average period of 63 months. Chromosomal alterations detected by comparative genomic hybridisation (CGH) were recorded in 37 of the 39 cases analysed. The most frequent CGH abnormalities were gains of 17p, 20q, 16p, 17q, 1p31, 7q21, and 9cen-q22, and losses of 9p21-pter and 13q21-22. However, the patterns of CGH imbalances did not allow the identification of a single common event, suggesting that the key initiating event(s) is not a numerical imbalance. Patients with tumours harbouring a gain of 17q showed significantly longer overall and disease-free survival (P=0.001 and 0.008) as well as lower frequency of metastasis (P=0.018) during follow-up. Taken together, the findings suggest that the clinical outcome of MFH is associated with the genetic profiles of the primary tumours. Importantly, a subgroup of MFHs characterised by a low risk of developing metastasis and local recurrence is recognised based on their frequent gains of 17q by CGH.

Immunohistochemical expression of extracellular matrix proteins and adhesion molecules in pancreatic carcinoma.

BACKGROUND/AIMS: Carcinoma invasion and metastasis in general involve multiple steps including dynamic changes in the composition and structure of extracellular matrix proteins and cell surface receptors. In the present study, the usually highly invasive carcinoma of the pancreas was investigated regarding the expression of various extracellular matrix proteins and their corresponding integrin receptors, as well as E-cadherin. METHODOLOGY: Phenotypic expression of various markers was investigated immunohistochemically in frozen sections of 16 pancreatic carcinomas and normal pancreatic tissue. RESULTS: An irregular and discontinuous deposition of type IV collagen and laminin in the basement membrane was found in cancer tissue and a pronounced desmoplastic reaction with deposition of type I, type III, and type IV collagen in the tumor stroma. In contrast, the noninvolved pancreas showed an intact basement membrane and a sparse stroma. The collagen type IV and laminin receptors alpha 2, alpha 3, and beta 1 integrin subunits were expressed on pancreatic cancer cells but not the alpha 6 integrin subunit normally present on epithelial cells, suggesting anchorage independence of the carcinoma cells. An increased capacity for cancer cell motility was suggested by the abundant expression of the "antiadhesive" extracellular matrix proteins, tenascin and vitronectin close to the cancer cells, and the expression of cell surface receptors such as alpha v (vitronectin-binding). Expression of the alpha 4 integrin subunit was also increased on cancer cells. CONCLUSIONS: The distribution of extracellular matrix proteins and the cell surface immune phenotype differed in pancreatic carcinoma as compared to normal pancreatic tissue. The present findings substantiate the notion that disseminated growth of highly malignant carcinomas of the pancreas reflects an invasive interaction of the tumor cells with extracellular matrix proteins of a well-established stroma. Similar findings were observed regardless of tumor histology and patient survival time.

Pattern of distribution and prognostic value of angiogenesis in pancreatic duct carcinoma: a semiquantitative immunohistochemical study of 45 patients.

In specimens obtained from resected pancreata, the intratumoral microvessel density (IMD), the proliferation rate of the neoplastic parenchymal cells, and their p53 protein expression were assessed. The sources of errors were great in the measurements of the IMD. This statement can be illustrated by the finding that when the IMD was calculated by manual counting in five areas of intense neovascularization (hot spot regions), using x200 and x400 magnifications, the numbers of microvessels per square millimeter were 65+/-23 and 106+/-8, respectively, which reflects a significant difference. Two patterns of microvessel distribution could be identified: one with hot spots only in the stroma (n = 19) and one in which the hot spots were located in areas of neoplastic parenchyma (including its stroma) (n = 26). The IMD was significantly greater in the latter group. There was no general correlation of neoplastic disease with the IMD. However, when a scoring system was used to assess the angiogenesis, hot spots in areas of neoplastic parenchyma were associated with a greater proliferation rate of the tumor cells, and with a short length of survival of the patients from their neoplastic disease.

Aspects of percutaneous fine-needle aspiration biopsy in the diagnosis of pancreatic carcinoma.

BACKGROUND: Morphologic verification of malignancy is usually a prerequisite before initiating nonsurgical therapy for pancreatic carcinoma. Fine-needle biopsy has been widely used, but the method has also been criticized because of inadequate sampling material and the risk of intra-abdominal seeding. METHODS: Cytologic material from 334 patients with suspected pancreatic malignancy was evaluated with regard to the sensitivity, specificity, and overall accuracy of the technique. The outcome (positive versus negative yield of cancer cells) was also entered in a Cox bivariate regression analysis and tested against multiple prognostic variables. RESULTS: In all, 270 patients had malignant disease, which was verified cytologically in 187. The sensitivity, specificity, and accuracy were 69%, 100%, and 75%, respectively. Statistically significant prognostic factors with regard to patient survival time were type of therapy (P <0.001), tumor location (P <0.001), jaundice (P <0.001), pain (P <0.001), and palpable mass (P <0.05). CONCLUSION: Fine-needle aspiration biopsy is still found to be a safe and feasible method for diagnosing pancreatic cancer, providing the requisite diagnostic information before initiating nonsurgical therapy.

Prognostic significance of Ki-67 antigen and p53 protein expression in pancreatic duct carcinoma: a study of the monoclonal antibodies MIB-1 and DO-7 in formalin-fixed paraffin-embedded tumour material.

Formalin-fixed paraffin-embedded material from 57 patients in whom curative resection of pancreatic carcinoma had been attempted was analysed by an immunohistochemical procedure to estimate proliferation and p53 protein expression. Using the monoclonal antibody (MAb) MIB-1, which recognizes a Ki-67 epitope, the proliferating cell index (PCI, percentage of immunoreactive tumour nuclei) and proliferating cell area (PCA, percentage of immunoreactive tumour nuclear area) were calculated using an interactive image analysis system and were compared with semiquantitative scoring of stainability. MAb DO-7, which recognizes both wild- and mutant-type p53 protein, was used to assess p53 expression in the same material. MIB-1 stainings were of high quality in 53 tumours. The median PCI was 29.7% (range 0.5-82.1%) and the median PCA was 10.6% (range 0.0-36.5%). There was a close correlation between PCI and PCA (P < 0.0001). PCI and PCA values were in conformity with the semiquantitative scoring (P < 0.0001). The p53 immunohistochemical stainings were successful in 48 tumours and the protein was expressed in 22 (46%). High PCI values (> 45%, n = 14) correlated with shorter survival time (P < 0.01). PCA (P < 0.05) and the expression of p53 protein (P < 0.001) were independent prognostic variables.

Combined use of nuclear morphometry and DNA ploidy as prognostic indicators in nonresectable adenocarcinoma of the pancreas.

The introduction of combined modality treatment has only marginally affected the prognosis in nonresectable pancreatic carcinoma. Evaluation of easily accessible prognostic variables could be of clinical importance when selecting patients for proper therapy. DNA ploidy and morphometric variables were chosen as prognostic markers and assessed on cytologic material obtained by fine-needle aspiration biopsy (FNAB) from 128 patients with pancreatic carcinoma. The nuclear DNA content was measured by image cytometry. Patients were categorized as short-term (< or = 6 mo) and long-term survivors (> 6 mo). Ninety-eight of 116 nonresectable patients were possible to evaluate. There were significant differences between short- and long-term survivors with regard to DNA ploidy (p < 0.01) and the morphonuclear variable anisokaryosis (p < 0.001). In patients with either DNA aneuploid tumors or anisokaryosis > or = 0.6, the survival time was 6 mo or less in 85 and 93%, respectively. When both these criteria were fulfilled, only 5% survived for more than 6 mo. Thus, DNA ploidy and morphometry, separately or in combination, may provide prognostic information in nonresectable pancreatic carcinoma.

MR imaging of adult colo-rectal intussusception. A case report.

MR imaging of an intussuscepted sigmoid cancer misinterpreted as a rectal carcinoma is described. High-resolution technique with pelvic-phased array coils and fast spin-echo was used. The diagnosis is discussed in relation to the MR findings.

Prognostic significance of DNA ploidy in pancreatic carcinoma.

The nuclear DNA content was assessed by image cytometry on cytologic specimens obtained with fine-needle aspiration biopsy in 96 patients with pancreatic duct carcinoma. Twenty-two of these patients had pancreaticoduodenal resection. According to DNA analysis there were 27 (28%) diploid, 17 (18%) tetraploid, and 52 (54%) aneuploid tumors. The corresponding patient median survival times were 8, 5, and 4 months, respectively. Resectable tumors were more often DNA diploid (10 of 22) than nonresectable tumors (17 of 74) (p < 0.05). A Cox multivariate regression analysis demonstrated that surgical resection (p < 0.001) and diploid DNA pattern (p < 0.05) were factors associated with longer patient survival time. Although the difference in survival time was small, the data indicate that DNA diploid tumors represent a less aggressive subset of pancreatic carcinoma.

Morphometric characteristics in adenocarcinoma of the pancreas and chronic pancreatitis.

BACKGROUND: Morphometric analysis whereby size and form of cellular nuclei are transformed into quantities has previously been shown to be a valuable adjunct to the histopathologic differential diagnosis between chronic pancreatitis and pancreatic carcinoma. The present study aims to assess the clinical value of morphometry performed on cytologic material from benign and malignant pancreatic lesions. METHODS: Cytologic specimens from 100 patients with the diagnosis of pancreatic carcinoma and 15 patients with chronic pancreatitis were evaluated by interactive morphometry using a digital image analyzer system. RESULTS: There were significant differences (p < 0.001) for all morphometric variables between the malignant and benign groups (mean area p 50, 135.41 microns 2 versus 69.66 microns 2; anisokaryosis, 0.74 versus 0.41; and polymorphism, 0.13 versus 0.09). CONCLUSIONS: Morphometry may be used as a complementary tool in the cytologic diagnosis of pancreatic carcinoma.

Haemodynamic effects of pneumoperitoneum and the influence of posture during anaesthesia for laparoscopic surgery.

The laparoscopic operating technique is being applied increasingly to a variety of intra-abdominal operations. Intra-abdominal gas insufflation, i.e. pneumoperitoneum (PP), is then used to allow surgical access. The haemodynamic effects of PP in combination with different body positions have not been fully examined. Eleven patients without signs of cardiopulmonary disease were studied before and during laparoscopic cholecystectomy under propofol-fentanyl anaesthesia with controlled ventilation. Swan-Ganz and radial arterial catheterization were used to determine haemodynamic data in the horizontal position, with a 15-20 degree head-down tilt and a 15-20 degree head-up tilt. The measurements were repeated after insufflation of carbon dioxide to an intraabdominal pressure of 11-13 mmHg, as well as during surgery. The ventricular filling pressures of the heart were strictly dependent on body position. PP in the horizontal position increased pulmonary capillary wedge pressure by 32% (P < 0.01), central venous pressure by 58% (P < 0.01), and mean arterial pressure by 39% (P < 0.01). When PP was combined with a head-down tilt, there was a further increase in filling pressures by approximately 40% (P < 0.01), while the reduction in filling pressures during the head-up tilt was counteracted by PP. During PP with a head-up tilt, the filling pressures did not differ from those in the horizontal position without PP. CI showed a certain dependency on filling pressures. It is concluded that PP causes signs of elevated preload and afterload. The combination of PP and a head-up tilt is associated only with signs of an elevated afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile duct pressure, hormonal influence and recurrent bile duct stones.

An obstacle to the outflow from the bile duct not only increases bile duct pressure but also facilitates the formation of primary bile duct stones. The bile duct pressure, an indicator of the balance between bile inflow and outflow, was studied postoperatively under similar conditions in 123 patients, who had been operated on for bile duct stones. Secondary bile duct stones had been present in 86 patients (group CC) and primary stones in 26 (group C), while 11 without sphincter of Oddi function were used as a control group. The basal bile duct pressure was similar in groups CC and C, but significantly lower in the controls. Intraductal injection of saline solution caused a similar increase in bile duct pressure in groups CC and C, but not in the controls. Intravenous administration of secretin and somatostatin increased the bile duct pressure in groups CC and C, while a "normal" response to cholecystokinin, a decrease in bile duct pressure, was observed only in group CC. The "abnormal" response to cholecystokinin found in group C indicates a motor dysfunction of the sphincter of Oddi, which may have been responsible for, or at least contributed to, the formation of recurrent bile duct stones in this group.

Serum levels of CA 19-9 and CA 50 in relation to Lewis blood cell status in patients with malignant and benign pancreatic disease.

Serum expression of the cancer-associated antigens CA 19-9 and CA 50 and their relation to Lewis blood cell status were studied in 26 patients with pancreatic duct carcinoma and 26 patients with pancreatitis. The discriminating capacity between benign and malignant disease was high for both tumor markers. The correspondence between serum levels of CA 19-9 and CA 50 was close irrespective of the Lewis phenotype of the patient. All cancer patients with normal levels of CA 19-9 and CA 50 were of the phenotype Le(a-b-). Knowledge of the Lewis phenotype may therefore add vital information when tumor marker assays are used for diagnosis and monitoring of malignant pancreatic disease.

Endoscopic clearance of the pancreatic duct in chronic pancreatitis with severe pain.

In a phase I study endoscopic removal of pancreatic duct stones and protein plugs was attempted in five patients suffering from chronic pancreatitis with severe chronic pain. The pancreatic duct contents could be extracted after successful sphincterotomy in three patients. Clearance of the pancreatic duct was followed by complete or partial relief of pain. The follow-up period was 17-48 months. Endoscopic extraction is, however, not without complications; it is technically difficult, and many attempts may be required. The combination of endoscopic therapy and extracorporeal shock-wave lithotripsy may be a better alternative.

Clinical relevance of tumour markers CA 19-9 and CA-50 in sera from patients with pancreatic duct carcinoma.

Serum levels of the tumour antigens CA 19-9 and CA-50 and their relation to the extent of the disease were studied in 97 patients with carcinoma of the pancreas. Of 13 patients with normal serum concentrations of CA 19-9, 11 (84.6%) had irresectable disease, whereas 87.5% of the patients with resectable disease expressed antigen levels above cut-off. Following attempted radical surgery, preoperatively elevated serum levels decreased in eight patients (50%). Unchanged and high levels were associated with residual disease and early death. Clinical signs of recurrence were preceded by elevated serum levels of both tumour antigens.

Histopathologic and cytochemical characteristics of interval breast carcinomas from the Stockholm Mammography Screening Project.

Combined morphological and cytochemical malignancy grading in addition to tumor stage was applied to assess the malignant potential of so-called interval carcinomas from the Stockholm randomized mammography screening study. Only interval carcinomas surfacing within two years from screening were included. Fifty-four percent of the tumors were in stage I and 46% of the carcinomas eligible for DNA analysis were diploid, i.e. low-malignant. An overrepresentation of prognostically unfavorable tumor characteristics was found only within the subgroup 'true' and 'early' interval cancer.

Interval cancer and survival in a randomized breast cancer screening trial in Stockholm.

The aim of the present study was to analyse the survival rate in a group of breast cancers detected in the intervals between screening examinations in relation to clinically detected cancers in a non-screened population. All interval and control cancers were recruited from a randomized controlled mammography screening trial in Stockholm. The overall survival up to eight years of observation was higher in 191 patients with interval cancers than in 142 control cancers (p = 0.01). There were no significant differences between the two groups with regard to tumor size, stage distribution, or mean age, though the interval group did have a larger proportion of younger women. The similarity was confirmed by multiple regression analysis. The overall survival stage by stage was consistently higher in interval cancers. The survival rate in the true interval cancers was similar to that for those found in retrospect to have been detectable or traceable at the time of screening. No correlation was found between the length of the interval and the survival of patients with interval cancers. These results contradict the hypothesis that a high growth rate is associated with a poorer prognosis and that interval cancers are a more aggressive form of breast neoplasia.

DNA ploidy in screening-detected non-palpable mammary carcinomas.

Non-palpable breast cancers detected by mammography in women participating in the ongoing screening project at Södersjukhuset, Stockholm, Sweden, were classified by morphological and cytochemical malignancy grading. The women's age ranged between 40 and 64 years, and the clinical course was followed for a minimum of 5 years after primary treatment. No significant difference in disease-free survival was observed in the 66 cases studied (mean age 58 years) where 28% of the tumors were aneuploid and 72% euploid. Our results indicate that prognosis, even for patients with potentially highly malignant tumors, can be altered when their tumors are detected and treated at an early stage.

Intratumoral variations in DNA distribution patterns in mammary adenocarcinomas.

Correlated flow-cytometric (FCM) and microspectrophotometric (MSP) techniques were applied to investigating whether intratumoral variations in the DNA distribution patterns of 21 primary mammary adenocarcinomas can occur. Although neoplastic cell populations with both diploid and tetraploid (i.e., euploid) distribution patterns could be found in varying proportions in some of the tumors, there was no evidence in any tumor nodule for the presence of euploid populations in one part and aneuploid populations in another. This statement was based on the results of the MSP technique, where the assessments were made on cytodiagnostically identified neoplastic cells. Also, when applying the FCM technique the statement was found to be essentially valid; only one of the tumor nodules showed a DNA distribution pattern that, by means of the criteria used in this procedure, was defined as being both euploid and aneuploid. Here, however, the technique consists of assessments made on a great number of microscopically non-identified cells. It was concluded that when conflicting reports are given from different laboratories on the prognostic value of the cytochemically assessed DNA distribution patterns in breast carcinomas, they are not likely to be attributed to intratumoral DNA heterogeneity but, rather, to differences in the methods used and in the criteria applied for the so-called ploidy assessments.

Aneuploidy as a prognostic factor in breast cancer.

The predictive value of nuclear DNA content in mammary carcinoma is still under debate in spite of several reports indicating a relationship between DNA ploidy and prognosis. The impact of differences in methodology on the evaluation of DNA data is discussed, and a recent study demonstrating DNA ploidy as a statistically significant prognostic variable on a prospective material of breast cancer patients is presented.

Non-palpable invasive breast carcinomas from the Stockholm screening project.

Sixty-six non-palpable, invasive mammary adenocarcinomas from the Stockholm mammography screening project were studied with respect to histopathology. In 53 of these tumors estrogen receptor (ER) content was estimated and in 30 of them also the DNA distribution pattern. The tumors were predominantly of low or intermediate histological malignancy grade and ER-rich, whereas the distribution of DNA ploidy equalled that found in a non-selected tumor material. Only 2 tumors recurred during follow-up (median 51 months), indicating that non-palpable breast carcinomas represent a prognostically favourable subset in spite of a relatively high proportion of aneuploid tumors.