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Leukaemia evoked with 7,8,12-trimethylbenz(a)anthracene in rat. 3. Changes in lymphoid tissues.

Profound changes in the level of certain dehydrogenase enzymes were observed in lymphoid tissues of rats involved by erythroblastic stem cell leukaemia. In lymphoid tissues free of leukaemic involvement, activity of malate dehydrogenase (MDH) always exceeded that of lactate dehydrogenase (LDH). In those which contained substantial infiltrates of leukaemic cells, activity of LDH was increased while MDH activity was reduced. In leukaemic spleen significant changes were observed in the molecular forms of LDH; the proportion of LDH-5 (muscle-type LDH) was greatly increased while the other molecular forms were reduced. The spleen of rats with leukaemia exhibited a marked increase in the normal level of aerobic and anaerobic glycolysis but the rate of respiration was unchanged.The terminal stages of stem cell leukaemia in the rat are characterized by wide-spread leukaemic infiltration of liver and other tissues. Lymph node involvement, however, was found to be selective. Coeliac lymph nodes greatly exceeded other lymph node groups in their incidence of leukaemic involvement. It is considered that the selective nature of lymph node involvement in stem cell leukaemia derives from topographical considerations.

Animals↗

Malignant perivascular epithelioid cell tumour ("PEComa") of soft tissue: a unique case.

Tumours of perivascular epithelioid cells (PEComas) are being increasingly reported at visceral and somatic sites. Both benign and malignant variants have been identified, although clinical follow-up is often limited, which prevents meaningful predictions of behavior. We report the case of a malignant soft tissue PEComa with histologically confirmed regional lymph node metastases and radiologically confirmed pulmonary metastases. The light microscopic appearance and immunohistochemical profile (HMB-45, smooth muscle actin positive) and electron microscopic appearance support perivascular epithelioid cell differentiation.

Aged↗

Outcome of surgical resection for chest wall recurrence in breast cancer patients.

BACKGROUND: Although recurrent breast cancer is a systemic disease, there might be several exceptions where local treatment has a favorable outcome. METHODS: From 1989 to 1996, 15 patients underwent full thickness chest wall resection, supported by peri- and postoperative systemic treatments for patients with isolated chest wall recurrences, including soft tissue local recurrence and parasternal lymph node metastasis. RESULTS: The 5-year survival rate after surgical removal was 47%. Patients with > 5-year disease-free intervals (DFI) after mastectomy showed a long survival after chest wall resection. Local failures appeared in four cases whose surgical margins were positive. No serious complication except one pyothorax occurred after surgery. CONCLUSIONS: It is suggested that surgical treatment with a full thickness chest wall resection might have a favorable prognosis for selected patients with solitary lesion and long DFI.

Adult↗

Evaluation of malignancy and the prognosis of esophageal cancer based on an immunohistochemical study (p53, E-cadherin, epidermal growth factor receptor).

The subjects in this study consisted of 40 preoperative untreated esophageal squamous cell carcinoma patients. While p53 did not significantly correlate with the clinicopathological factors, E-cadherin significantly correlated with lymphatic invasion, vascular invasion, the depth of invasion, the degree of lymph node metastasis, the histological stage, and the number of lymph node metastases. Epidermal growth factor receptor (EGFR) significantly correlated with age, the depth of invasion, and the number of lymph node metastases. The 5-year cumulative survival rate was 45.7% in the p53-positive cases and 61.9% in the p53-negative cases, with no significant difference, and 87.8% in the E-cadherin-positive cases and 19.1% in the -negative cases, and the difference was significant. The prognosis was significantly poor in EGFR-positive subjects: the 5-year survival rate was 38.6% in EGFR-positive cases and 68% in -negative cases. The 5-year survival rate in E-cadherin-negative, EGFR-positive cases was 0%, while it was 91.7% in the reverse pattern, and this difference was significant. These findings suggest that both E-cadherin and EGFR are important prognostic factors, and a more precise prognosis can thus be obtained by combining them. Such a combined technique may be very useful as an indicator for grading the biological malignancy of esophageal cancer.

Adult↗

Presence of human herpesvirus-8 DNA sequences and overexpression of human IL-6 and cyclin D1 in inflammatory myofibroblastic tumor (inflammatory pseudotumor).

Inflammatory myofibroblastic tumor (IMT) is composed of myofibroblasts, plasma cells, and lymphocytes. Cytokines are possibly involved in its pathogenesis. Human herpesvirus-8 (HHV-8) encodes cell cycle regulatory and signaling proteins. A combination of nested PCR with several negative controls and Southern blot methods showed the presence of HHV-8 DNA in seven cases of IMT. Additionally, strong expression was demonstrated by in situ hybridization in many tumoral nuclei. Most of the myofibroblasts in all of the cases were immunoreactive for human IL-6 and cyclin D1. These cytokines probably have a paracrine action and may sustain myofibroblastic growth. HHV-8 could play an essential role in triggering IMT development by a local reactivation of viral lytic replication. The relationship between HHV-8 and immunosuppression status as the only associated cause for tumorigenesis should be revised.

Adult↗

Neuroendocrine pancreatic tumours: clinical presentation, biochemical and histopathological findings in 84 patients.

A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 35 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominal symptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.

Adenoma, Islet Cell↗

A randomised trial of vindesine plus interferon-alpha 2b compared with interferon-alpha 2b or vindesine alone in the treatment of advanced malignant melanoma.

60 patients were entered into a randomised study comparing vindesine (3 mg/m2/week) plus interferon-alpha 2b (6 U/m2 3 times per week) to vindesine alone or to interferon alone for the treatment of metastatic malignant melanoma. Patients receiving the combination therapy arm (schedule A; vindesine plus interferon-alpha 2b) showed a complete and partial response rate of 8/20 (40%) which was significantly higher (P < 0.05) than that achieved with either single-agent treatment schedule. In addition, patients receiving the combined treatment schedule had a significantly prolonged survival (median 19 months) when compared to a median of 10 months for interferon alone and 5 months for vindesine alone. The combination was generally well tolerated with only additive toxicity. It is concluded that combination treatment regimens utilising interferons together with chemotherapeutic agents deserve further study in the treatment of metastatic malignant melanoma.

Combined Modality Therapy↗

Docetaxel plus cisplatin is effective for patients with metastatic breast cancer resistant to previous anthracycline treatment: a phase II clinical trial.

BACKGROUND: Patients with metastatic breast cancer (MBC) are frequently exposed to high cumulative doses of anthracyclines and are at risk of resistance and cardiotoxicity. This phase II trial evaluated the efficacy and toxicity of docetaxel plus cisplatin, as salvage chemotherapy in patients with MBC resistant to prior anthracyclines. METHODS: Patients with MBC that had progressed after at least one prior chemotherapy regimen containing anthracyclines received docetaxel 75 mg/m2 followed by cisplatin 60 mg/m2 every 3 weeks for a maximum of 6 cycles or until disease progression. RESULTS: Between Jan 2000 and May 2002, 24 patients with tumors primary resistant and 15 with secondary resistant disease were accrued. All 39 patients were evaluable for safety and 36 for efficacy. The objective response rate was 31% (95% CI, 16-45%) with 3 complete responses. The median time to disease progression was 7 months, and the median overall survival was 23 months (median follow-up of 41 months). Neutropenia was the most frequently observed severe hematologic toxicity (39% of patients), whereas asthenia and nausea were the most common non-hematologic toxicities. No treatment-related death was observed. CONCLUSION: In conclusion, we found docetaxel plus cisplatin to be an active and safe chemotherapy regimen for patients with MBC resistant to anthracyclines.

Adult↗

[Direct current therapy for local control of malignant tumors].

Sixteen malignant tumors of soft tissue (15 cases) were treated with low voltage direct current (DC therapy) with or without systemic chemotherapy. Two platinum or stainless steel electrodes were placed in the tumor and around 10 volts of direct current was passed for 1 hour. In cases in which chemotherapy was performed, single or combined anticancer agents consisted of ADM and BLM were administered simultaneously with DC therapy by systemic route. Ten cases (11 tumors) out of 15 cases received no other local treatment. Histological examination was performed in 6 of 11 lesions, and in all lesions pathological therapeutic effects were recognized. Decrease in tumor size was observed in 9 lesions. In 2 cases the tumors disappeared completely after DC therapy only. In one case receiving DC therapy with chemotherapy, the tumor decreased dramatically and became resectable. Main complications were slight pain during treatment and slight fever after treatment, but special treatment for these complications was not necessary. Our results suggested that DC therapy with or without systemic chemotherapy was useful for local control of malignant tumors. And also if DC therapy had been performed simultaneously with chemotherapy the therapeutic effects seemed to be more emphasized than single use of these therapies.

Adult↗

High resolution ultrasound characterization of soft tissue masses in children.

Forty-two soft tissue masses in infants and children were examined with high resolution ultrasonography. Sonography was diagnostically specific in 17/42 (40%), useful but not diagnostic in 24/42 (58%), and misleading in 1/42 (2%) of soft tissue masses. Lesions with diagnostic sonographic features included cystic hygroma, fibromatosis colli, lymphadenopathy with abscess formation, and one case of osteomyelitis.

Abscess↗

Carcinogenic activity in rats of combined treatment with cyclophosphamide, methotrexate and 5-fluorouracil.

A total of 240 outbred Sprague-Dawley rats were treated with 3 different doses of the cyclophosphamide-methotrexate-5-fluorouracil (CMF) regimen adopted from clinical chemotherapy studies in breast cancer patients. Eighty untreated rats served as controls. Individual and total doses of the drugs applied were lower than corresponding doses used in human adjuvant therapy protocols compared on a mg/m2 basis. Lifelong observation of the animals demonstrated a strong dose-related carcinogenic response to the tested scheme. Main target organs of treatment-related neoplasms were the nervous system, the hematopoietic and lymphatic tissue, the urinary bladder, and the suprarenal gland. It is concluded that the CMF drug combination evokes carcinogenic responses in several organ systems in the rat and should be regarded as representing a carcinogenic risk to humans. Uncritical clinical use of the three-drug protocol should be avoided.

Adrenal Gland Neoplasms↗

[Ultrasonography of tumors of the locomotor system].

Sonography is an integral part of primary tumor diagnosis and follow-up for the great majority of organ systems. However, its value in the field of space-occupying processes of the locomotor system, especially of malignant bone tumors, has mostly been underestimated. The sonographic examination has to investigate the whole tumor region and the corresponding lymph nodes statically and dynamically. The examination procedure should be standardized and the documentation reliable. Evaluation criteria are the localization, dimensions, and volume of the tumors, echogenicity and homogeneity, peri- and intratumoral vascularization (vessel density and architecture), borders of the tumor, and neighboring structures. Pathologic changes not only of the soft tissues but also of the bones can be evaluated sonographically. Even subtle analysis does not permit definitive assessment of tumor status. Taking its physical limitations into consideration, high-resolution sonography, enhanced by color/PowerDoppler and three-dimensional techniques, is a valuable adjunct to improve diagnosis, therapy planning, monitoring, and posttherapeutic care of tumors of the locomotor system.

Bone Neoplasms↗

Guidelines for the use of ultrasound in the head and neck.

The values and limitations of ultrasound of the head and neck in general, and with respect to the different regions of the neck, are described. In addition, the place of ultrasound examination in the work-up of patients with an elusive neck mass is defined.

Biopsy, Needle↗

NESP55, a novel chromogranin-like peptide, is expressed in endocrine tumours of the pancreas and adrenal medulla but not in ileal carcinoids.

Neuroendocrine secretory protein 55, NESP55, is an acidic protein belonging to the chromogranin family. The distribution of NESP55 in human tumours is not known. The aim of the present study was to study the expression of NESP55 in human gastrointestinal, pancreatic and adrenal tumours. A total of 118 human endocrine and nonendocrine tumours were examined by immunocytochemistry, and compared to the expression of chromogranin A (CgA) in the same tumours. Pancreatic endocrine tumours (14 out of 25), pheochromocytomas (19 out of 19), and neuroblastomas (seven out of 14) expressed NESP55, with the same strong labelling pattern in both benign and malignant tumours. Expression of NESP55 in pancreatic endocrine tumours and pheochromocytomas was confirmed by Western and Northern blot analysis. Immunocytochemical analysis demonstrated no labelling in ileal carcinoids (zero out of 15), and adrenocortical adenomas (zero out of 15). The majority of gastrointestinal and pancreatic carcinomas were negative for NESP55, with focal staining observed in two out of 30 tumours. In contrast, CgA was present in all neuroendocrine tumours examined (25 out of 25 pancreatic endocrine tumours, 19 out of 19 pheochromocytomas, 14 out of 14 neuroblastomas and 15 out of 15 ileal carcinoids). Thus, the expression of NESP55 in endocrine tumours of the gastrointestinal tract, pancreas and adrenals differs from that of CgA. Neuroendocrine secretory protein 55 is found in a subset of neuroendocrine tumours showing differentiation towards adrenal chromaffin cells and pancreatic islets cells.

Adolescent↗

Locally metastasizing vascular tumor. Spindle cell, epithelioid, or unclassified hemangioendothelioma?

The authors report the case of a 2-year-old boy with a recurrent and locally metastasizing, spindle cell, vascular tumor with histiocytoid cells involving the skin, subcutaneous tissue, and muscle of the right forearm, the right distal radius and ulna, and multiple lymph nodes of the right axilla. Diagnoses of hemangioma, hemangiopericytoma, angiomatosis, spindle cell hemangioendothelioma, and malignant hemangioendothelioma were made on successive excision specimens. The soft tissue of the right arm became diffusely enlarged, and a severe syndrome developed that was similar to that described by Kasabach and Merritt. The limb was amputated above the elbow, the axillary lymph nodes were cleared, and a total dose of 6,000 centigrays axillary radiation was given. After operation, the Kasabach-Merritt syndrome resolved. Despite the lymph node metastases and multiple tissues involved, the patient has remained well 6 years after surgery. Although the tumor exhibited some of the histologic features of a spindle cell hemangioendothelioma, the low-grade aggressive behavior resembled that of an epithelioid hemangioendothelioma. The reported case cannot be classified into any of the recognized categories or subdivisions of vascular tumors.

Bone Neoplasms↗

[Occupational neoplasms in Poland in the years 1971-1994].

The analysis of the incidence of malignant neoplasms, recognised as occupational disease, in Poland during the years 1971-94 was based on occupational disease certificates sent obligatory to the Nofer institute of Occupational Medicine (Lódz) by all sanitary and epidemiological stations under the Ministry of Health and Social Welfare and the Polish State Railways. During the period study 1118 occupational neoplasms were diagnosed, including 1042 cases (93.2%) of neoplasms in males. Among males malignant Ineoplasms of lung (36.1%), larynx (25.5%), bladder (14.7), skin (6%), lymphatic and haematopoietic tissue (3.4%) and pleura (2.9%) were most common. The rate occupational neoplasms in the total number of neoplasms registered accounted for 0.11% in males and 0.01% in females. PAH (29.1%), asbestos dust (18.8%), ionizing radiation (13.8%), chromium and its compounds (13.5%) and benzidine (9.8%) belong to the most frequent causes of malignant neoplasms in males, and ionizing radiation (31.5%) and asbestos dust (30.3%) in females. The number of neoplasms recognised as occupational disease is very low. Underestimation of occupational neoplasms is very common throughout the world, but it is particularly high in Poland if we take the incidence of pleura mesothelioma as an example. This is mainly due to: (1) the lack of clinical and morphological specificity of occupationally induced neoplasms; (2) a long latency; (3) the influence of other factors confounding the effect of occupational exposure; (4) a relatively small number of occupational carcinogens identified thus far; (5) limited knowledge of occupational carcinogens and criteria for occupational disease certification, and unsatisfactory interviewing skills among doctors who diagnose cancer disease. The identification of a harmful factor and the size of exposure to it, belongs to the weakest point in certifying the occupational background of the disease. The essential conclusions presented stress the urgent need for establishing the system facilitating the diagnosis and certification of occupational neoplasms.

Adolescent↗

Frequent loss of membranous E-cadherin in gastric cancers: A cross-talk with Wnt in determining the fate of beta-catenin.

The potential correlation of E-cadherin reduction and Wnt2 up-regulation in determining the intracellular distribution of beta-catenin in gastric cancers was investigated by the methods of frozen tissue array-based immunohistochemistry, Western blot and RT-PCR analysis. It was revealed that membranous E-cadherin was reduced frequently in the two major subtypes of gastric cancer (intestinal gastric cancer, i-GC and diffuse gastric cancer, d-GC) and closely correlated with the risk of lymphoid node metastasis (P < 0.05). The reduction of membranous E-cadherin was paralleled with cytosolic and nuclear accumulation of beta-catenin and the increased Wnt2 expression. These results indicate that the reduced E-cadherin is a common genetic phenotype of GCs and plays beneficial roles in tumor metastasis. Altered beta-catenin distribution may result from the imbalance of E-cadherin production and Wnt expression, which confers on gastric cancer cells more aggressive behaviors.

Cadherins↗