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PubMed1988

Patterns of metastatic spread following resection of extremity soft-tissue sarcomas and strategies for treatment.

This study examines recurrence patterns in 255 patients with soft-tissue sarcoma treated with preoperative chemotherapy and radiation, followed by limb-sparing surgery. Eighty-five patients developed metastatic disease: 13 had isolated local recurrence, 43 had isolated pulmonary metastases, 11 had metastases to lung and elsewhere, and 18 had metastases to multiple sites. Of the patients with isolated pulmonary metastases, 19/43 had resection of the metastases, and 9 are disease free. All 13 patients with local recurrences had resection of the recurrence, and 9 remain disease-free. Patients with multiple sites of recurrence had a 2-year survival of less than 10%. Resection of metastases is beneficial to a small number of patients who develop metastatic disease.

Actuarial Analysis↗

PubMed1979

Ganglioside patterns of metastatic and non-metastatic transplantable hepatocellular carcinomas of the rat.

In previous investigations, we correlated levels of sialic acid, gangliosides, and ganglioside glycosyltransferases with tumorigenesis over a 24-week continuum of growth of hepatocellular neoplasms of the rat induced by the carcinogen N-2-fluorenylacetamide. However, metastatic tumors developed only rarely and were not analyzed. To investigate surface changes associated with metastasis, well-differentiated and poorly differentiated hepatocellular carcinomas were transplanted to syngeneic recipient rats. From those, several metastatic and nonmetastatic isolates were obtained and compared. Both total and ganglioside sialic acid amounts in transplantable hepatomas were elevated above control liver values but were significantly lower for metastatic lines than for nonmetastatic lines. The nonmetastatic lines were characterized by ganglioside patterns depleted in the precursor ganglioside GM3 (sialic acid-galactose-glucose-ceramide) and elevated in the products of the monosialoganglioside pathway. In contrast, metastatic isolates exhibited a restoration of GM3 and nearer normal amounts of other gangliosides. The findings point to differences in sialic acid-containing glycolipids, comparing metastatic and nonmetastatic hepatocellular carcinomas, and further extend the concept that ganglioside alterations do not cause tumorigenesis but are the end result of a cascade of events which apparently continue beyond the onset of metastasis.

2-Acetylaminofluorene↗

PubMed1984

Identification of a surface antigen, common to murine lung and Lewis lung carcinoma, by monoclonal antibody.

Lewis lung carcinoma (3LL) is a spontaneous murine lung carcinoma which preferentially metastasizes into the lung. Monoclonal antibodies (MAb) against 3LL cells were prepared by fusing spleen cells from rats immunized with 3LL and the P3-NSI/I-Ag4 (NSI) plasmacytoma. Two hybridomas were selected which secreted antibodies capable of preferential binding to 3LL cells and not to other malignant cells. Immunohistochemical staining of sections prepared from various mouse organs with one of the MAbs (22.2), revealed exclusive staining of the lung tissue. The data suggest that a lung-specific, 3 LL-associated antigen, is detected by the 22.2 MAb on 3LL cells. The 22.2 antigen is a surface molecule, and is stable following trypsin treatment and fixation by glutaraldehyde or picric acid. Cells that were prepared from a subcutaneous tumor or from lung metastases express high amounts of 22.2 antigen compared to cells of the culture 3LL line (3LLC). Upon reinoculation of 3LLC cells into mice there was a gradual increase in 22.2 antigen expression. It was possible to select from the heterogeneous 3LLC cell population several clones which express high amounts of antigen. These clones differed also in their metastatic patterns. However, the metastatic capacity of these clones did not correlate with expression of the 22.2 antigen. Thus, it appears that expression of the 22.2 antigen is not a necessary condition for formation of lung metastases by 3LL.

Animals↗

PubMed2005

Injection of colorectal cancer cells in mesenteric and antimesenteric sides of the colon results in different patterns of metastatic diffusion: an experimental study in rats.

BACKGROUND: This experimental study was designed to investigate the differences in pattern of local growth and diffusion of colorectal cancer cells injected into either mesenteric (M) or antimesenteric (AM) sides of the colon. METHODS: A total of 1 x 10(6) colonic adenocarcinoma cells (line DHD/K12-TRb) were injected into the cecal wall of BDIX syngeneic male rats at an M or AM site of the colon. At six weeks after injection, all animals were sacrificed and the presence or absence of tumor in the cecum as well as regional metastasis and peritoneal carcinomatosis were determined. RESULTS: Six weeks after injection, macroscopic tumor growth was observed in 27/37 (72%) animals in group M and 21/32 (65%) in group AM (P = 0.98). In group AM, diffuse peritoneal carcinomatosis was present in 19/21 rats (90.4%) versus 3/27 rats (11%) in group M; this difference was statistically significant (P = 0.025). Regional mesenteric lymph nodes were the only location in which tumor was detected in 23/27 rats (85%) in group M versus 2/21 (9.5%) in group AM; this difference too was statistically significant (P = 0.031) CONCLUSION: The patterns of diffusion of tumors implanted in mesenteric and antimesenteric sites of the colon appear to be different, although the reason for this is not clear.

Journal Article↗

PubMed2005

Chemokine receptors 6 and 7 identify a metastatic expression pattern in squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck (HNSCC) metastasizes predictably to locoregional, cervical lymph nodes. Tumor cells can express various receptors that facilitate metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCRs), normally expressed on lymphocytes, control immune and inflammatory cell migration, providing a link between innate and adaptive immunity. CCR expression was evaluated in HNSCC, and we showed a consistent pattern of CCR6 downregulation and upregulation of CCR7 in metastatic cells and tissues. Functional assays indicate that these surface receptors were functional on metastatic tumor cells. CCR6 downregulation is consistent with its decreased expression in cells emigrating from peripheral mucosal sites, while CCR7, important for homing of immune cells to secondary lymphoid organs, was significantly upregulated. Thus, CCR6, CCR7 and their ligands, normally important in controlling immune cell trafficking in response to inflammatory stimuli, may have an important role in determining the metastasis of HNSCC cells in vivo. Our data indicate that inhibition of CCR signaling may provide a targeted molecular therapy to prevent HNSCC metastasis.

Biomarkers, Tumor↗

PubMed1991

Cytokeratin expression patterns in metastatic transitional cell carcinoma of the urinary tract. An immunohistochemical study comparing local tumor and autologous metastases.

The cytokeratin (CK) expression patterns of local, ie, primary or recurrent, high-grade-malignant transitional cell carcinomas (TCCs) of the human urinary tract and autologous lymphogenic and hematogenic metastases (n = 33) were compared. Special attention was paid to CK expression in the tumor invasion front and other areas where tumor-stroma interaction occurred to visualize cell populations with a metastatic phenotype. For this purpose, polypeptide-specific monoclonal antibodies to CKs 4, 7, 8, 10, 13, 14, 16, 17, 18, and 19 were used, employing the immunoperoxidase method. Results show that: 1) An increased expression of CK8 and CK18 is seen in the TCC tumor cells at the interface with peritumoral stroma in the tumor invasion front and with intratumoral stroma ('interface phenomenon'). Other than reflecting a quantitative change, this phenomenon might be explained by unmasking of CK8 and CK18 epitopes occurring in these regions. 2) Although in general the expression of CK13 in local TCC is decreased with increase of histopathologic parameters for progression, ie, grade and stage, an extensive proportion of CK13-positive tumor cells still can be found in some TCCs, even in metastases. 3) Morphologically recognizable types of aberrant differentiation in TCC, i.e., pseudosarcomatous or squamous differentiation and marked loss of differentiation, show altered expression of many of the CKs studied.

Carcinoma, Transitional Cell↗

PubMed1984

Stage IB adenocarcinoma of the cervix: metastatic potential and patterns of dissemination.

The metastatic potential patterns of dissemination have been investigated in 150 patients with Stage 1B adenocarcinoma of the cervix treated during a 20-year period from 1956 to 1977. All cases with the exception of one were treated with a combination of intracavitary radium implants followed by a radical surgical procedure with pelvic lymph node dissection. It was found that the incidence of pelvic metastases and distant recurrences and the survival rates were the same as in previously published reports for squamous cell carcinomas treated in the same manner. In one respect adenocarcinomas showed a significant difference when compared with squamous cell cancers: The incidence of residual tumor in the hysterectomy specimens after intracavitary treatment was much higher (30% versus 11%). This is considered a strong argument for surgical treatment of patients with early stages of adenocarcinoma of the cervix.

Adenocarcinoma↗

PubMed1982

Ultrasound patterns of metastatic tumors in the gallbladder.

Eleven cases of sonographically detected metastatic disease to the gallbladder are reported. This paper represents the first comprehensive review of the ultrasonographic findings in this not infrequently encountered disease process. Four distinctive sonographic diagnostic patterns have evolved and are described. The suspicion of metastatic tumors in the gallbladder should be raised, particularly in the presence of focal gallbladder wall thickening in association with nonshadowing intraluminal soft tissue masses. In contrast to primary carcinomas of the gallbladder, cholelithiasis usually is absent. The differential diagnosis, which includes various benign conditions of the gallbladder, is discussed.

Adult↗

PubMed1991

Patterns of growth and metastases of induced pancreatic cancer in relation to the prognosis and its clinical implications.

To understand high malignancy of pancreatic cancer, the growth and metastatic patterns of pancreatic cancer induced in Syrian hamsters were examined. In this model, induced tumors resemble the human disease morphologically, clinically, biologically, and immunologically. In the current study, primary-induced cancer and transplants of pancreatic cancer cell line (PC-1) into the SC tissue or pancreas of homologous hosts were used. In the primary-induced pancreatic cancer, perineural invasion was the most common path (88%), followed by lymphogenic (31%) or vascular (2%) metastases. Inoculation of PC-1 cells into the pancreas resulted in 100% tumor take within 3 weeks. Of 19 intrapancreatic allografts, all showed peritoneal invasion, 5 (26%) liver metastases, 3 (16%) lymph node metastases, 17 (89%) perineural invasion, and none vascular invasion. Even microscopic tumors were found to metastasize primarily via perineural spaces. It was also demonstrated, for the first time, that cancer cells take this route to reach distant tissues, including the lymph nodes. Intraductal spreading occurred in both primary cancers and intrapancreatic allografts either continuously or discontinuously. The patterns of discontinuous intraductal tumor expansion imitated tumor multicentricity. Although perineural invasion was the most common feature of primary cancer and intrapancreatic allografts, lymphatic, hepatic, and vascular invasion and metastases usually occurred in advanced cases. Environmental factors seem to influence expansion and metastases, as evidenced by differences in growth and in metastatic patterns between SC and intrapancreatic allografts.

Animals↗

PubMedDate not supplied

[Adjuvant chemotherapy following liver metastasis resection in neoplasms of the colorectum].

INTRODUCTION: Adjuvant chemotherapy after hepatic resection of colorectal metastases has been advocated because of the significant risk of tumor recurrence. Data presented in literature show unequivocally that the probability of recurrence and tumor-related death exceeds survival. Although the initial site of disease recurrence varies, both intrahepatic and extrahepatic organs are at risk for tumor progression. PATIENTS AND METHODS: To reduce the risk of tumor progression after hepatic resection of colorectal metastases, multiple chemotherapy approaches have been designed. Treatment approaches have varied by chemotherapeutic agents, route and schedule of administration, and duration. RESULTS: A significant difference in survival between patients treated by resection alone and resection with adjuvant chemotherapy is not evident from these data. DISCUSSION: Metastatic inefficiency is a major driving force in the development of metastatic patterns. Then, the probability of synchronous seeding (from primary colorectal carcinomas) of hematogenous metastases in the liver, lungs, and other organs is less than metachronous seeding, in which only liver metastases are predominantly seeded from the hepatic metastases, and arterial metastases are predominantly seeded from the pulmonary lesions. This sequential development of metastatic patterns creates windows of potential therapeutic opportunity during which metastatic disease is confined to the liver alone. CONCLUSION: The risk of recurrence after hepatic resection of colorectal metastases clearly warrants further prospective study of adjuvant therapy to improve survival. Future trials of adjuvant therapy after hepatic resection of colorectal metastases must address the patterns of tumor recurrence and account for adjuvant chemotherapy given previously, after resection on the primary colorectal carcinoma.

Chemotherapy, Adjuvant↗

PubMed2001

The pattern of metastasis of human melanoma to the central nervous system is not influenced by integrin alpha(v)beta(3) expression.

We investigated the effect of integrin alpha(v)beta(3) expression on the metastatic pattern of human melanoma cells in the central nervous system (CNS). For this purpose, we developed a hematogenous CNS melanoma metastasis model in nude mice using a modified internal carotid artery infusion technique. This protocol revealed 2 different patterns of CNS metastasis. The integrin alpha(v)beta(3)-expressing melanoma lines Mel57 and Zkr nearly exclusively produced metastases in the brain parenchyma, whereas cells of the BLM and MV3 lines, devoid of integrin alpha(v)beta(3) expression, preferentially metastasized to dura mater and leptomeninges. Treatment with hyaluronidase to obtain single BLM cell suspensions did not influence the metastatic pattern, indicating that this was not simply the result of entrapment of tumor cell aggregates in large-sized leptomeningeal vessels. The role of integrin alpha(v)beta(3) expression in the process of metastasis was tested by transfection of BLM, but did not lead to an altered pattern of metastasis. We did observe, however, slower growth of the transfected tumors, although the in vitro growth rate was unaltered, indicating a reduction in tumorigenicity. We conclude from our findings that CNS metastasis of melanoma cells in the mouse xenograft model occurs in at least 2 different but very reproducible patterns. Although it is predicted that adhesion of tumor cells to endothelial cells plays a role in this phenomenon, tumor cell integrin alpha(v)beta(3) expression per se does not explain the difference in metastatic behavior in the CNS. We assume that other, as yet unknown factors, must be involved.

Animals↗

PubMed1999

Unique distribution patterns of metastatic lymph nodes in patients with superficial carcinoma of the thoracic oesophagus.

BACKGROUND: Lymph node metastasis is commonly found in carcinoma of the thoracic oesophagus, even when the tumour invades only the submucosa. Although lymph node status greatly influences the outcome, the pattern of early lymphatic spread has not been investigated, and the role of lymph node dissection is still a matter of controversy. METHODS: A series of 110 patients with superficial carcinoma who underwent systematic extended lymph node dissection was investigated retrospectively. RESULTS: Lymph node involvement was found in 0 per cent (none of nine), 23 per cent (five of 22) and 49 per cent (38 of 78) of tumours that invaded the lamina propria, muscularis mucosa and submucosa respectively. Anatomically distant lymph nodes (recurrent nerve nodes and perigastric nodes) were involved more frequently than other intrathoracic nodes adjacent to the main tumour. Only three patients had involvement limited to the intrathoracic group, and in carcinoma that invaded only the muscularis mucosae, all metastatic nodes were located at the thoracocervical junction or in the abdomen. The 5-year survival rate was 89 per cent in the node-negative group and 54 per cent in the node-positive group (P < 0.0003). CONCLUSION: The recurrent nerve nodes and perigastric nodes are the principal proximal regional lymph nodes involved in superficial carcinoma of the thoracic oesophagus. Systematic lymph node dissection, which included these nodes, yielded an acceptable and favourable outcome in patients with node-positive superficial carcinoma.

Carcinoma, Squamous Cell↗

PubMed1986

Morphologic variations of small cell lung cancer. A histopathologic study of pretreatment and posttreatment specimens in 104 patients.

A consecutive series of 104 autopsies on patients treated in protocol for small cell carcinoma of the lung (SCCL) was studied with respect to metastatic pattern at autopsy in relation to pretreatment WHO 1981 classification, and extent and significance of non-SCCL tumor tissue at autopsy. The only significant difference in the metastatic pattern at autopsy between patients with pretreatment oat cell or intermediate subtype was metastases to the brain. Thus, the frequency of brain metastases was 17/35 (49%) in patients with oat cell type compared to 2/18 (11%) in patients with intermediate type (P less than 0.05). At autopsy 13 of 98 patients (13%) had non-SCCL tumor tissue in at least one site. These patients had a significantly shorter survival (P = 0.020) compared to patients with pure SCCL at autopsy. Furthermore, none of these 13 patients had obtained complete remission. Whether these morphologic variations had been present at the pretreatment stage of the disease or were due to the chemotherapeutic treatment could not be solved in the present study. However, the results might indicate that mixed SCCL/non-SCCL histology is a negative prognostic factor in the treatment of SCCL. Prospective studies including more extensive pretreatment tissue sampling seem to be required.

Adult↗

PubMed2001

The pattern of metastatic lymph node dissemination from adenocarcinoma of the esophagogastric junction.

BACKGROUND: The incidence of adenocarcinoma of the esophagogastric junction is rapidly increasing, and the extent of lymphadenectomy for such tumors remains controversial. The aim of this study was to identify the pattern of dissemination by examination of all lymph nodes retrieved from resected tumors of the esophagogastric junction. METHODS: The endoscopic and pathologic reports of patients who underwent RO resection for adenocarcinoma of the esophagogastric junction between January 1996 and November 1999 were examined. Patients with type 1 tumors (distal esophagus) underwent subtotal esophagectomy with 2-field lymphadenectomy. Patients with type 2 (gastric cardia) tumors underwent transhiatal D2 total gastro-esophagectomy. Lymph node groups were dissected from the main specimens and examined separately. RESULTS: One hundred and four type 1 and 48 type 2 tumors were studied. Median nodal recovery was 23 lymph nodes (type 1, 22 lymph nodes; type 2, 23 lymph nodes). Seventy-eight percent of the type 1 tumors with nodal metastases had dissemination in both the abdomen and mediastinum. The common abdominal sites were the paracardiac and the left gastric stations. Within the mediastinum, paraesophageal, paraaortic and tracheobronchial metastases were more often encountered. Type 2 tumors had positive lymph nodes most frequently in the left and right paracardiac, lesser curve (N1 group), and left gastric (N2 group) territories. Nodal status correlated with increasing depth of tumor invasion (P =.002). CONCLUSIONS: The pattern of nodal dissemination for cardia tumors concurs with that described by other studies. The current definition of nodal fields in the abdomen and mediastinum for esophageal tumors relates to experience with squamous carcinomas. Our results demonstrate a different pattern of dissemination for junctional esophageal adenocarcinomas. The nodal stations to be resected in radical lymphadenectomies for such tumors should be redefined.

Adenocarcinoma↗

PubMed1995

Metastatic behavior of human tumors in congenitally athymic nude mice: intrinsic properties of the tumor cells and host immune reactivity.

Congenitally athymic nude (nu/nu) mice have been used extensively as hosts to study the metastatic properties of xenografted human tumors. It has not been fully explored to what extent the metastatic behavior of human tumor xenografts reflects the intrinsic properties of the tumor cells and to what extent it is influenced artificially by the host. The purpose of the work reported here was to evaluate the potential usefullness of athymic mice for qualitative and quantitative assessment of the intrinsic metastatic properties of human tumor cells. Four human melanoma cell lines (A-07, D-12, R-18, U-25) were included in the study. Quantitative intradermal and intracranial transplantation assays were used to determine the tumorigenicity and immunogenicity of the cell lines. The metastatic behavior of the cell lines was studied by inoculating cells intra-arterially or intravenously (artificial metastases) or intradermally (spontaneous metastases). The influence of the host on the incidence of metastases was assessed by inoculating cells intravenously in immunologically modified athymic mice. Both the intradermal and intracranial tumorigenicity differed substantially between the cell lines. The host immune reactivity against heterotransplantation was significantly lower for D-12 than for A-07, R-18 and U-25 cells. The incidence of metastases was influenced significantly by the host immune reactivity. The cell lines showed organ-specific metastatic patterns in athymic mice. The organs of preference were lungs for A-07 and D-12 cells, lymph nodes for R-18 cells, and brain for U-25 cells. The organ-specific metastatic pattern in athymic mice reflected the pattern of distant metastases in the donor patients. In addition, all cell lines gave rise to metastases in abdominal organ sites, but without organ specificity. The incidence of abdominal metastases was influenced significantly by the tumorigenicity of the cell lines. In conclusion, athymic mice appear to be excellent hosts for assessment of the organ specificity in the metastatic behavior of human tumors. The metastasis frequency of human tumors in athymic mice, however, might be a misleading quantitative measure of the intrinsic metastatic propensity of the tumor cells, owing to the cell-line-dependent host immune reactivity.

Animals↗

PubMed1996

Renal cell carcinoma metastases. Review of unusual clinical metastases, metastatic modes and patterns and comparison between clinical and autopsy metastatic series.

We reviewed all cases of unusual clinical metastases of renal cell carcinoma found in the English literature. The percentages of usual and unusual clinical metastases are compared with data of some large autopsy series. The involvement of various organs is considered and some metastatic modes and patterns are reported. The analysis shows that clinical metastases are obviously underdiagnosed. Correct staging based on careful clinical investigations is paramount for optimal management of metastatic renal cancer.

Autopsy↗

PubMed1989

Unusual CNS and orbital metastases of neuroblastoma.

Although neuroblastoma is a common childhood malignancy with frequent metastatic disease, involvement of the CNS and eye are unusual findings. Recently, we encountered two such cases. One of the patients had undergone bone marrow transplantation. The long term effects of this treatment regarding behavior of the tumor and subsequent metastatic pattern have yet to be determined. The second patient presented with apparent congenital neuroblastoma. Both of these tumors were extremely aggressive in nature, and could represent variations of the usual metastatic pattern of neuroblastoma.

Abdominal Neoplasms↗

PubMed2001

[Cutaneous malignant melanoma in the area of the head and neck with intermediate tumor thickness: does primary site have prognostic relevance?].

BACKGROUND: Tumor thickness and infiltration of malignant melanoma are the main prognostic factors for recurrence and survival. The sentinel lymph node biopsy may provide a step toward a more individual staging and therapy. It was the aim of this study to investigate the prognostic influence of the primary localization of head and neck melanoma subdivided into scalp, ear, neck, and face. To form a basis for routine sentinel lymph node biopsy in case of intermediate tumor thickness metastatic pattern of the different primary sites were analysed. METHOD: Survival rates depending on primary tumor site of 51 patients with cutaneous malignant melanoma of the head and neck were analysed. Metastatic pattern were evaluated with the help of clinical, intraoperative, pathohistologic data. RESULTS: Scalp and ear melanoma were found to be higher risk lesions with a 5-year survival rate of 28% and 59% respectively. Melanoma of the neck and face had a 5-year survival rate of 75% and 78% respectively. In two cases of ear melanoma lymph node metastases could be demonstrated in unusual sites by skipping the first draining basin. In three cases bilateral metastases could be shown histologically as opposed to clinical prediction. CONCLUSIONS: Localization of cutaneous malignant melanoma of the head and neck is a prognostic factor for survival. Because of the discordancy between clinical prediction and lymphatic drainage pattern sentinel lymph node biopsy improves accuracy of diagnostic and therapeutic procedures.

Follow-Up Studies↗