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The genetic background modifies the spontaneous and X-ray-induced tumor spectrum in the Apc1638N mouse model.

The effect of the genetic background on the tumor spectrum of Apc1638N, a mouse model for attenuated familial adenomatous polyposis (FAP), has been investigated in X-irradiated and untreated F1 hybrids between C57BL/6JIco-Apc1638N (B6) and A/JCrIBR (A/J), BALB/cByJIco (C) or C3H/HeOuJIco (C3). Similar to the ApcMin model, the Apc1638N intestinal tumor multiplicity seems to be modulated by Mom1. Moreover, several additional (X-ray-responsive) modifier loci appear also to affect the Apc1638N intestinal tumor number. The genetic background did not significantly influence the number of spontaneous desmoids and cutaneous cysts in Apc1638N. In general, X-irradiation increased the desmoid multiplicity in Apc1638N females but had no effect in males. The opposite was noted for the cyst multiplicity after X-rays. Surprisingly, X-irradiated CB6F1-Apc1638N females were highly susceptible to the development of ovarian tumors, which displayed clear loss of the wild-type Apc allele.

Adenomatous Polyposis Coli↗

Microsurgical composite reconstruction in head and neck and esophagus.

This paper describes-the indications for, the main points of the surgical technique, and the results of composite reconstruction using a combination of pediculated and free tissue units, which has allowed extensive and complex reconstruction following resection of malignant tumors in the head and neck region or in the esophagus. Composite reconstruction was indicated for synchronous or metachronous carcinomas in the head and neck region and the esophagus (Groups 1 and 2) or for secondary reconstruction of the esophagus (Group 3). In most cases, the gastric tube or colon was used as pediculated tissue, and the jejunum, forearm flap, or rectus abdominis flap were used as free tissue. Total necrosis of the transplanted jejunum occurred in two patients and leakage in five, most of whom were in Group 3. Although the prognosis was extremely poor in Groups 1 and 3 because of the advanced cancer stage, composite reconstruction permitted oral feeding, which proved beneficial from the viewpoint of the patient's quality of life.

Aged↗

The risk of tumor induction in man following medical irradiation for malignant neoplasm.

A review of second malignant tumors (S.M.T.s.) following therapeutic irradiation formalignant neoplasm in man is presented. Twenty-one new cases are added to the literature, 3 of adenocarcinoma of the endometrium following treatment for squamous cell carcinoma of the cervix, 3 of adenocarcinoma of the large bowel following treatment for squamous cell carcinoma of the cervix, 9 S.M.T.s in irradiated oropharyngeal or oral mucosa, and 6 single cases of S.M.T.s following radiotherapy of cancers in other sites. It is suggested that there is relatively low incidence of S.M.T.s among patients formalignancy, but the risk remains to be established by an appropriate study of controland test populations.

Adenocarcinoma↗

Fine structure of a radiation-induced osteogenic sarcoma.

An osteogenic sarcoma arose in the right orbit of a 7-year-old boy some 5 years after the right orbit had been treated by four courses of radiotherapy (total dose approximately 13,000 rads) for a multicentric retinoblastoma. Death occurred 6 months after the orbital tumor was first detected. Study of the orbital tumor by electron microscopy revealed a cell population of varied morphology in which two main types were identified. In one group, the cells were large with radiolucent cytoplasm, which contained long branching segments of rough endoplasmic reticulum. In the second group, the cells were smaller with irregular nuclei and an electron-dense cytoplasm, which contained short segments of dilated rough endoplasmic reticulum and numerous mitochondria. The first group of cells closely resembled osteoblasts, while the second group had some features of osteoclasts or their percursors. The branching processes of the tumor cells were separated by an amorphous ground substance, which contained collagen-like fibrils and hydroxyapatite crystals. Crystal deposition was in some instances in close relation to extracellular membrane-bound vesicles.

Cell Nucleus↗

Decreased risk of radiation-associated second malignant neoplasms in actinomycin-D-treated patients.

One hundred two long-term survivors of childhood cancers with second malignant neoplasms (SMNs) were collected from 10 institutions. Forty-seven cases fulfilling study criteria were studied to determine the risk of developing a SMN in irradiated fields after exposure to various chemotherapeutic agents. The case control method was used. The risk of developing such tumors was decreased by a factor of 7 in patients receiving actinomycin-D (AMD). The "protective" effect of AMD was more pronounced in patients receiving repeated courses of the agent. No change in relative risk was found for children given antifolates, the vinca alkaloids, or alkylating agents. AMD "protection" is an unexpected finding because the agent is an oncogen in animals and an enhancer of radiation, the latter being a known carcinogen. Possible mechanisms, which remain speculative, are discussed. These results indicate the need for careful long-term observation of cancer survivors to gain understanding of the late effects of multimodal treatments.

Child↗

Multiple granulocytic tumors of the skin: report of six cases of myelogenous leukemia with initial manifestations in the skin.

The clinical and pathologic findings in six patients with myelogenous leukemia presenting initially as multiple granulocytic tumors of the skin were reviewed. The skin of the trunk was most commonly involved with multiple, confluent erythematous plaques and soft, tender, non-ulcerated, violaceous nodules. Two patients had been treated for malignant lymphoma eight and nine years prior to the onset of skin lesions (Hodgkin's disease and nodular lymphocytic lymphoma, respectively), and cutaneous granulocytic leukemia developed in sites of irradiated skin. The skin biopsies in all cases were originally misinterpreted by the pathologist as malignant lymphoma and the correct diagnosis of granulocytic leukemia was not established in any of the cases until overt extracutaneous involvement was detected. The interval in the six patients from skin biopsy to definite involvement of blood and bone marrow by acute granulocytic leukemia ranged from three weeks to six months with a mean interval of 3.8 months. The mean duration of survival from the diagnosis of extracutaneous dissemination was 12.7 months (range of three months to two and one-half years). Poorly differentiated myelogenous leukemia was demonstrated at postmortem examination in all cases. Cytochemical stains of formalin-fixed, paraffin-embedded tissues confirmed the granulocytic origin of the neoplasm: leukemic cells in skin biopsies, bone marrow aspirates, and autopsy specimens contained abundant naphthol AS-D chloracetate esterase. The findings indicate that granulocytic leukemia may rarely present with skin tumors as the original manifestation of the disease. Recognition of the distinctive clinical, histopathologic, and enzyme histochemical features of the lesion provide a basis for distinguishing granulocytic sarcoma of the skin from mycosis fungoides and other cutaneous malignant lymphomas.

Acetates↗

Acute and late effects of multimodal therapy on normal tissues.

The increasing use of combined radiation, chemotherapy, and surgery had led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined.

Antineoplastic Agents↗

Patterns of second malignant neoplasms in children.

A search of the records of 10 pediatric oncology centers revealed 102 children with more than one malignant neoplasm. In this group of 102 patients, all pediatric cancers were seen as initial lesions, but Wilms' tumor and retinoblastoma were over-represented and leukemia and brain tumors underrepresented. Survival variation as well as tumor susceptibility may be responsible for this disproportion. Osteosarcomas and chondrosarcomas were the most frequent second malignant neoplasms (SMN). Embryonal tumors were rare as SMN and adult-type tumors (carcinomas) appeared at earlier than expected ages, whether arising after irradiation or not related to that form of therapy. Radiation was associated with 69 SMN, genetic disease accounted for 27 SMN and both conditions were noted in 15 SMN. In the group of 21 patients for whom neither radiation nor a known genetic disorder could be implicated, there were three with colon carcinoma and glioma and five with leukemia or lymphoma and glioma. These combinations may reflect new tissue-specific hereditary cancer syndromes.

Adolescent↗