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PubMed1975

Increased incidence of cerebral metastases in sarcoma patients with prolonged survival from chemotherapy. Report of cases of leiomysarcoma and chondrosarcoma.

Soft tissue and bony sarcomas rarely metastasize to the central nervous system, particularly to the cerebral hemispheres. In 456 patients with metastatic sarcoma, only 6 (1.3%) had cerebral metastases documented by brain scan at the time of referral for chemotherapy. Adriamycin-containing combination chemotherapeutic regimens have led to a significant increase in the median survival of patients from the start of chemotherapy (18 + months for responders compared, to 7 months in nonresponders). Of 14 patients relapsing after a response or stabilization of disease of 6 months or greater, the cause of relapse was the development of cerebral metastases in 5 (36%). Two of these cases, one a patient with leiomyosarcoma and one with chondrosarcoma, were documented by autopsy and are reported in detail because of their rarity in the medical literature. Although the numbers are small, the increased incidence of cerebral metastases in the group relapsing after a lengthy response suggests that improved chemotherapy for sarcomas resulting in improved survival may be chaning the pattern of metastatic disease, and may require new the;apeutic approaches.

Adult↗

PubMed1982

Altered organization of cell-substrate contacts and membrane-associated cytoskeleton in tumor cell variants exhibiting different metastatic capabilities.

The pattern of cell-substrate attachment and the organization of actin-containing microfilament bundles were analyzed in tumor cell variants of the K-1735 melanoma and UV-2237 fibrosarcoma series exhibiting distinct metastatic phenotypes. In both tumors, the low-metastatic cells were relatively flat, with well-developed focal contacts. Visualization of the cellular organization of actin and vinculin by fluorescence microscopy indicated that the low-metastatic cells contained prominent stress fibers which terminated in large vinculin-containing focal contacts. The high-metastatic cells were characterized by poor organization of vinculin and adhesion plaques as well as by low number and disarray of actin bundles. These results are compatible with the notion that cytoskeletal organization may be involved in cytodynamic processes related to tumor cell dissemination and implantation.

Animals↗

PubMed1994

Leptomeningeal tissue: a barrier against brain tumor cell invasion.

BACKGROUND: Primary brain tumors are characterized by an extensive infiltrative growth into the surrounding brain tissue. This process is confined to the central nervous system, and tumor cell metastasis to other organs is rare. However, other tumors of non-neural origin may frequently metastasize to the central nervous system. PURPOSE: The purpose of the present study was to examine the invasive behavior of different glioma cells into tissues of neural (brain aggregates) as well as non-neural origin (leptomeningeal tissue). Using the same target tissues, the invasive characteristics of two neural metastatic tumors (one malignant melanoma and one small-cell lung carcinoma) were also studied. This direct comparison of the invasive behavior between tumors of neural and non-neural origin provides valuable information regarding the mechanisms of glioma cell dissemination in the central nervous system. METHODS: The in vitro invasive behavior of human tumors of the central nervous system into human leptomeningeal tissue as well as into normal rat brain tissue was studied. For this purpose, a co-culture system consisting of tumor biopsy specimens, human leptomeningeal cell aggregates, and brain cell aggregates was established. Three glioblastomas, one oligodendroglioma, one meningioma, one small-cell lung carcinoma, and one malignant melanoma were studied. RESULTS: In co-cultures of gliomas and leptomeningeal cell aggregates, a well-defined border between the two tissues was observed. The brain cell aggregates, in contrast, were consistently invaded by the glioma cells. The brain metastases showed a different invasion pattern. The metastatic cells invaded and progressively destroyed leptomeningeal cell aggregates, whereas they did not invade the brain cell aggregates. Upon confrontation of the leptomeningeal tissue with the meningioma, a fusion of the two tissues was observed. Immunostaining of the leptomeningeal tissue showed a strong expression of the basement membrane components fibronectin, collagen type IV, and laminin with no expression of glial fibrillary acidic protein, neuron-specific enolase, or S-100 protein. CONCLUSIONS: The present study indicates that there may be important biologic differences between the invasive behavior of gliomas and non-neuroepithelial tumors. Our co-culture experiments suggest that leptomeningeal cells and associated acellular components may constitute a barrier against glioma cell invasion. However, this barrier may not be functional for metastatic tumors to the brain. The presence of glioma cells within the leptomeninges should not necessarily be taken as evidence of aggressive growth or as an indicator of malignancy.

Animals↗

PubMed2003

Breast cancer metastatic to abdomen and pelvis: role of surgical resection.

OBJECTIVE: The purpose of this study was to describe the characteristics and outcome of women with metastatic breast cancer to the abdomen and pelvis, and to assess the role of surgical resection of abdominal and pelvic metastasis in this disease. METHODS: We retrospectively reviewed the medical records of 59 women with documented metastatic breast cancer to the abdomen or pelvis who had exploratory surgery by the Gynecology Service between 1986 and 2001. RESULTS: Exploratory surgery was performed a median of 5 years (range, 0-25 years) after initial diagnosis of breast cancer. Median survival from diagnosis of abdominal disease was 23 months, and 5-year survival was 24%. Survival was 36 months for optimally debulked patients (<2 cm of residual disease) and 20 months for suboptimally debulked patients (P = 0.07). Patients diagnosed 5 or more years after initial breast cancer diagnosis had a median survival of 36 months versus 17 months if diagnosed earlier (P < 0.01). On multivariate analysis the time to recurrence of breast cancer in the abdomen and optimal debulking were both significant variables. Hazard ratio for dying of disease if recurring before 5 years was 2.7 (CI 1.45-5.03) [P < 0.01]. Hazard ratio for dying of disease if suboptimal debulking was achieved was 2.14 (CI 1.13-4.02) [P = 0.02]. CONCLUSIONS: The disease pattern of metastatic breast carcinoma to the abdomen and pelvis does not appear to effect survival. Survival in patients where optimal debulking is achieved and in those recurring late is improved. Surgical resection of metachronous metastatic breast cancer to the abdomen and pelvis may be an important component of the management of this disease and should be considered in candidate patients.

Abdominal Neoplasms↗

PubMed1987

Villin: a cytoskeletal protein and a differentiation marker expressed in some human adenocarcinomas.

We studied the expression of villin, a microfilament-associated, actin-binding protein typical of brush-border microvilli, in a variety of human carcinomas by applying immunofluorescence microscopy to frozen sections and immunoblotting methods to tissue extracts using a rabbit antiserum and a monoclonal antibody specific for villin. All of the 24 primary and metastatic colorectal adenocarcinomas tested were uniformly and strongly positive for villin, with the immunocytochemical labeling concentrated at the luminal cell margin. In poorly differentiated tumor areas, rudimentary tubules were stained. All of the six tubular adenocarcinomas of the stomach studied as well as two adenocarcinomas of the gall bladder and a hepatocellular carcinoma were also villin-positive. Villin was detectable in 12 of 14 adenocarcinomas of the pancreas; in some of these cases, its distribution was heterogeneous. Among 21 renal cell carcinomas investigated, positivity for villin was seen in nine of 13 clear cell tumors (especially those of grade II), and in all four chromophilic cell tumors; however, all four chromophobe cell tumors studied were negative. Four of 11 endometrial but none of nine ovarian carcinomas were (uniformly or focally) villin positive. Of 18 adenocarcinomas of the lung studied, one was uniformly and four focally positive for villin, while the remainder were negative. All of the other epithelial tumors studied, including 12 adenocarcinomas of the breast and seven epithelial or biphasic pleural mesotheliomas, were villin negative. Our results show that the expression of villin in intestinal epithelial cells is consistently maintained in their corresponding carcinomas, even when the organized brush-border structure has been lost. The presence of villin in some endometrial and pulmonary adenocarcinomas--in contrast to its absence in the respective normal epithelia--suggests that this protein is newly expressed during hyperplasia, dysplasia, or carcinogenesis. Determining the presence or absence of villin and its immunocytochemical staining pattern in metastatic adenocarcinomas may be of some help in determining the type and site of the primary tumor.

Adenocarcinoma↗

PubMed1999

Axillary nodal metastases in head and neck cancer.

BACKGROUND: Axillary node metastasis is an uncommon occurrence in squamous carcinoma of the upper aerodigestive tract. METHODS: The tumor registry of The Johns Hopkins University Department of Otolaryngology-Head and Neck Surgery contained four cases of metastasis to the axilla from head and neck primary sites. A retrospective review of these cases was performed. RESULTS: Each patient had been initially treated for cancer years earlier including surgery and radiation to the neck. A recurrent cancer or a new primary then developed in the upper aerodigestive tract prior to the development of the axillary metastases. CONCLUSIONS: The common course of disease in these patients suggests that alteration of the lymphatic anatomy by previous treatment may have caused a new pattern of metastatic spread upon reseeding from the mucosa, resulting in the axillary metastases. Routine surveillance of the axillae by physical examination and/or computerized imaging in at risk patients may permit the early diagnosis of axillary metastases.

Aged↗

PubMed2000

Bilateral radical neck dissection: results in 193 cases.

BACKGROUND AND OBJECTIVES: Indications of simultaneous bilateral radical neck dissection remains controversial. The main objectives of this analysis were to study: a) the frequency of postoperative complications, b) the patterns of metastatic lymph nodes in the surgical specimen, c) the predictive factors of neck recurrences, d) the prognostic factors related to overall survival. METHODS: A retrospective review of results in 193 consecutive patients submitted to a simultaneous bilateral radical neck dissection from 1960-1990. RESULTS: Postoperative complications occurred in 60.8% of the cases. The most frequent ones were: fistula, wound infection, flap dehiscence and necrosis. There were four postoperative deaths (2.7%). The lymph nodes most frequently involved were of the upper jugular and upper accessory groups. Only patients with lip and paranasal sinus tumors never presented metastatic nodes at Levels IV and V. Tumor recurrences were more common at the ipsilateral neck (13.5%) or at distant sites (12.4%). The predictive factors of neck recurrences were: age, N stage, ipsilateral metastasis at Level II, and contralateral metastasis at Levels II and IV. The overall 5-year survival rates for the two age groups, that is, younger than 40 and older than 40 years of age, were respectively, of 8.5% and 35.6% (P = 0.0296). There were no survivals among the group of patients with neck lymph nodes staged as N3 or Nx. The overall 5-year survival rates were significantly influenced by contralateral metastatic lymph nodes at any level. The results of multivariate analysis using the Cox regression technique, showed that Level II ipsilateral metastatic lymph nodes, Levels II and IV contralateral metastatic lymph nodes, and age were the independent predictors of the risk of death. CONCLUSIONS: This study demonstrates that simultaneous bilateral neck dissection has a high morbidity and should be contraindicated as an elective procedure. Further studies with selective neck dissections are warranted.

Adult↗

PubMed1976

Predictors of radiation response in lung cancer. A clinico-pathobiological analysis.

From February 1972 to July 1975, 200 lung cancer patients were seen at the University of Rochester Cancer Center's Division of Radiation Oncology; 40% had squamous cell tumors and 87.5% had advanced disease localized to the thorax. Of the 160 patients who completed treatment, 101 were treated with continuous therapy schedules, and 59 were treated with split-course schedules, and 59 were treated with split-course schedules; 40 patients did not complete treatment because of early metastatic disease or death. Radiation therapy was very effective in local tumor ablation. To assess local tumor response, doubling times were obtained in measurable lesions prior to treatment. The doubling times (DT) were 25 days for small cell cancers and 192 days for adenocarcinoma. More than 50% tumor shadow regression was a good prognosticator of local tumor response; this increased as the mean DT decreased. The order of kinetic increase in tumor ablation per histology was the opposite of the one-year survival results because of the metastatic spread patterns of the different tumors. Survival rates in lung cancer emerge as simplistic and inadequate to explain local radiation effectiveness. Survival is conditioned by stage, histology, and modality of treatment, total dose delivered, and local tumor response. Although the most effective treatment dose seems to be over 6000 rads, the most efficient schedules were split-course delivering lower tumor doses. This modality of treatment is proposed as the optimal schedule to be combined with other forms of therapy with the goal of achieving better survival.

Adenocarcinoma↗

PubMed1986

Involvement of the central nervous system by ovarian carcinoma.

Ovarian carcinoma rarely metastasizes to the central nervous system (CNS). Of 110 patients with epithelial ovarian carcinoma treated at the Northern Israel Oncology Center between the years 1979 and 1985, only five (4.5%) had CNS involvement. The median age of the patients with 54.5 years. All of them had treatment with cisplatin and Adriamycin (doxorubicin). The median duration from diagnosis to the development of brain involvement was 17 months. The median survival time was 28 months from diagnosis of carcinoma and 2 months from diagnosis of CNS disease. The increased incidence of this kind of metastasis in patients achieving local control of their advanced disease suggests that a change in the pattern of metastatic spread or the prolonged survival permits occult CNS metastases to become apparent. A routine computerized axial tomography (CAT) scan of the brain should therefore be performed on patients with ovarian carcinoma with prolonged survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Adjuvant radiotherapy versus combined sequential chemotherapy followed by radiotherapy in the treatment of resected nonsmall cell lung carcinoma. A randomized trial of 267 patients. GETCB (Groupe d'Etude et de Traitement des Cancers Bronchiques).

BACKGROUND: The effect of adjuvant chemotherapy after resection of nonsmall cell lung cancer (NSCLC) remains an unresolved question. METHODS: From October, 1982, to November, 1986, 267 patients with resected NSCLC were included in a randomized trial. The adjuvant allocated treatments were either postoperative radiotherapy, 60 Gy in 6 weeks (radiotherapy group = 129 patients), or three courses of postoperative COPAC (cyclophosphamide, doxorubicin, cisplatin, vincristine, lomustine) chemotherapy followed by a similar radiotherapy schedule (chemotherapy/radiotherapy group = 138 patients). RESULTS: The sex ratio (M:F) was 19/1; mean age was 57 +/- 9 years. According to postoperative staging, 8 patients were Stage I, 70 were Stage II, and 189 were Stage III. The histologic type was squamous cell carcinoma in 175 patients, adenocarcinoma in 57, and large cell carcinoma in 35. The minimum follow-up was 6 years. Four patients were lost to follow-up. Death was recorded in 233 patients. No significant difference was observed in terms of disease free interval (P = 0.47, log-rank test), or overall survival (P = 0.68, log-rank test). With respect to the first site of relapse, distant metastasis occurred more frequently in the radiotherapy group (P = 0.09, log-rank test) whereas local relapse occurred similarly in both groups (P = 0.27). An interaction was observed between lymph node involvement and treatment in terms of overall survival. CONCLUSIONS: The COPAC chemotherapy as postoperative treatment failed to improve overall survival in patients with resected NSCLC receiving postoperative radiotherapy but decreased the pattern of metastatic progression, mainly in the N2 patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Functional anatomy of the lymphatic drainage system of the upper aerodigestive tract and its role in metastasis of squamous cell carcinoma.

BACKGROUND: Although there is a significant understanding of the vascular anatomy of the upper aerodigestive tract (UADT), there is less detailed knowledge of the architecture and drainage patterns of the lymphatic system. Detailed knowledge of the lymphatic system is critical for understanding the role of sentinal node identification in the management of different cancers. METHODS: We have combined microscopic techniques with in vivo and in vitro lymphographic studies to survey the architecture and drainage patterns of the lymphatic system of the UADT in 850 organ specimens. RESULTS: These studies show an interaction of superficial and deep lymphatic networks that vary in density but have a constant distribution characterized by predictable patterns of lymph drainage into the regional lymph nodes. CONCLUSIONS: Detailed knowledge of the lymphatic system of the UADT contributes to a better understanding of the patterns of metastatic spread of carcinomas of the UADT and provides a strong rationale for the practice of sentinel node identification in the management of these tumors.

Carcinoma, Squamous Cell↗

PubMed2001

Do nodal metastases from cutaneous melanoma of the head and neck follow a clinically predictable pattern?

BACKGROUND: Potential lymphatic drainage patterns from cutaneous melanomas of the head and neck are said to be variable and frequently unpredictable. The aim of this article is to correlate the anatomic distribution of pathologically involved lymph nodes with primary melanoma sites and to compare these findings with clinically predicted patterns of metastatic spread. METHODS: A prospectively documented series of 169 patients with pathologically proven metastatic melanoma was reviewed by analyzing the clinical, operative, and pathologic records. Clinically, it was predicted that melanomas of the anterior scalp, forehead, and face could metastasize to the parotid and neck levels I-III; the coronal scalp, ear, and neck to the parotid and levels I-V; the posterior scalp to occipital nodes and levels II-V; and the lower neck to levels III-V. Minimum follow up was 2 years. RESULTS: There were 141 therapeutic (97 comprehensive, 44 selective) and 28 elective lymphadenectomies (4 comprehensive dissections, 21 selective neck dissections, and 3 cases in which parotidectomy alone was performed). Overall, there were 112 parotidectomies, 44 of which were therapeutic and 68 elective. Pathologically positive nodes involved clinically predicted nodal groups in 156 of 169 cases (92.3%). The incidence of postauricular node involvement was only 1.5% (3 cases). No patient was initially seen with contralateral metastatic disease; however, 5 patients (2.9%) failed in the contralateral neck after therapeutic dissection. In 68% of patients, metastatic disease involved the nearest nodal group, and in 59% only a single node was involved. CONCLUSIONS: Cutaneous malignant melanomas of the head and neck metastasized to clinically predicted nodal groups in 92% of patients in this series. Postauricular and contralateral metastatic node involvement was uncommon.

Head and Neck Neoplasms↗

PubMedDate not supplied

Nasal septal melanoma.

The controversial issues on management of nasal septal melanoma center around the extent of pretreatment evaluation. Probably the minimum required is a chest radiograph, CBC, and liver function test (Dr. Westbrook). The use of bone scan and CT scans of brain, lungs, and abdomen (Drs. Suen and Medina) is controversial and of little yield. Aside from distant metastasis to the lung, liver, and brain, the regional metastatic spread pattern includes the nodal groups of the buccal, submental, and submandibular areas, with the possibility of bilateral involvement. All consultants agreed that the primary tumor should be treated with a wide local excision; however, there is no agreement as to the extent of nodal groups included in the nodal dissection. No consultant recommended primary septal reconstruction. The use of postoperative radiotherapy in high-dose fractions remains experimental, in the protocol research stage.

Combined Modality Therapy↗

PubMed1978

Meningeal seeding from rhabdomyosarcoma of the head and neck with base of the skull invasion: recognition of the clinical evolution and suggestions for management.

Rhabdomyosarcomas of the head and neck may spread by diffuse local invasion, resulting in erosion of the base of the skull with possible extension to the leptomeninges, brain, and cranial nerves, as well as invasion of the ventricular system with possible intradural, extramedullary metastases anywhere along the neuraxis. Meningeal spread of tumor is difficult to eradicate, and nearly all patients reviewed died soon after meningeal disease was evident. Patients with erosion of the base of the skull or abnormal cranial nerve findings seem to have a risk of seeding the meninges with tumor. The clinical evolution of this pattern of metastatic spread is reviewed, diagnostic studies are recommended, and therapeutic considerations are discussed. Tentative treatment guidelines are also offered.

Ataxia↗

PubMed1984

Protocols based on steroid receptors: Great Britain.

Steroid receptors appear to have prognostic significance in operable and disseminated breast cancer, but not in primary locally advanced disease. Information on receptor status gives some indication of the pattern of metastatic disease. Absence of ER and PgR detect effectively patients who will not benefit from endocrine therapy and the presence of both receptors indicates the patients most likely to respond. Patients wih ER+ PgR- or ER- PgR+ tumours have an intermediate frequency of response to endocrine treatment. Receptor status is not a determinant of response to cytotoxic treatment.

Breast Neoplasms↗

PubMed1988

Late intensification with high-dose melphalan and autologous bone marrow support in breast cancer patients responding to conventional chemotherapy.

Fifteen patients with advanced breast cancer who had achieved either a good partial or a complete response to conventional chemotherapy were selected to receive intensification treatment with high-dose melphalan 140-200 mg/m2 (HDM). All patients received autologous bone marrow rescue. All patients experienced marked haematological toxicity, and most experienced moderate or mild gastrointestinal side effects. There were three treatment-related deaths. Of twelve assessable patients eleven have relapsed; median time to relapse after HDM is 7 months. Nine of these eleven have died from recurrent breast cancer. Of the three patients remaining alive, only one is disease-free, at 18 months after HDM. Analysis of the pattern of metastatic relapse suggests that recurrence was due to failure of HDM to eradicate residual disease in the patient, rather than reinfusion of viable tumour cells. Treatment intensification with HDM has not succeeded in prolonging survival in patients already in good remission.

Adolescent↗

PubMed1988

Cellular DNA content and metastasis pattern in colorectal carcinomas.

Tissue samples from primary tumours and metastases obtained from surgical specimens and autopsies were investigated by flow cytometry for their DNA content. Of the 149 cases investigated, 124 autopsy cases of colorectal carcinoma were suitable for study. The pattern of metastatic spread in each individual case was analysed with reference to the autopsy records. A subgroup of euploid primary tumours was observed which should be considered separately with regard to its biological behavior, tumour location and extent of metastases. In these tumours, the liver was the first and final organ of haematogenic metastatic spread at an above-random frequency and a grossly metastatic liver with less than 15% of residual normal parenchyma was present at the same time. Furthermore, we observed stem-lines deviating in ploidy from the primary tumour in the metastases of nine cases. This indicates the chromosomal heterogeneity of colorectal carcinomas.

Aged↗

PubMed1996

Intra-abdominal patterns of disease dissemination in colorectal cancer identified using radioimmunoguided surgery.

PURPOSE: Patterns of metastatic spread are difficult to determine with routine postoperative follow-up. This study was undertaken to evaluate two selected populations of colorectal cancer patients injected and screened with anti-tumor antibody. METHODS: Eighty-six evaluable patients with colorectal cancer underwent exploratory laparotomy with both traditional surgical exploration and radioimmunoguided surgery (RIGS) following injection of 125I-labeled CC49 monoclonal antibody. RIGS-positive tissue detectable with a handheld gamma-detecting probe was defined as tissue involved with the disease process. Comparisons were made between extent of disease using traditional exploration and extent using RIGS. RESULTS: In 41 patients with primary disease, traditional exploration detected 45 sites of disease (1.1 sites/patient) compared with 153 RIGS-positive sites (3.7 sites/patient). In 45 patients with recurrent disease, traditional exploration found 116 sites (2.6 sites/patient) vs. 184 RIGS-positive sites (4.1 sites/patient). Involvement by selected anatomic sites is shown below [Table: see text]. CONCLUSION: RIGS detected more tissue involved in disease process for all sites in both primary and recurrent disease except liver metastases. Areas with highest proportion of RIGS-positive tissue, the gastrohepatic ligament and celiac nodes, are rarely resected and are not pathologically examined. Positive RIGS localization of tumor antigen in these areas suggests more extensive dissemination of disease process.

Abdominal Neoplasms↗