Biomedical subjects

R Essner

Publications and source records attributed to R Essner.

At least 37 records · Page 2Linked to original sources

PubMed1999

Sentinel node localization in breast cancer.

The status of the axillary nodes is the strongest known prognostic variable in patients with early breast cancer, and is routinely used in planning postoperative therapy. Conventional axillary lymph node dissection is limited by sampling error and potential morbidity. Sentinel node techniques have revolutionized the management of axillary nodes. Accurate identification and focused histologic evaluation of the sentinel node allow accurate prediction of the tumor status of other axillary nodes, thereby avoiding the morbidity and expense of a complete axillary dissection in node-negative patients. Radiotracer techniques play an important role in the preoperative and intraoperative localization of the sentinel nodes. Optimal localization of the sentinel node requires the use of both preoperative lymphoscintigraphy and intraoperative radiosensitive probes. Lymphoscintigraphy also identifies patients with lymphatic drainage to sites other than the axilla, thereby allowing more appropriate treatment and follow-up in this subset of patients. Procedures for localizing sentinel nodes require an understanding of the kinetics of the radiopharmaceuticals or other tracers used and the detection devices employed in each institution. Both surgical and nuclear medicine personnel should understand these principles, and close cooperation between surgeons, nuclear medicine physicians, and pathologists is essential for the application of sentinel node techniques.

Breast Neoplasms↗

PubMed1999

Lymphatic mapping and sentinel lymphadenectomy after wide local excision of primary melanoma.

BACKGROUND: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) are generally avoided in patients who have already undergone wide local excision (WLE) of a primary melanoma, because of concern that disruption of the cutaneous lymphatics might alter lymphatic flow to the sentinel node. We reviewed carefully chosen patients who had undergone LM/SL after WLE to identify circumstances that might make this approach otherwise safe and clinically accurate. STUDY DESIGN: From our melanoma database of 8,300 patients, of whom 1,015 had undergone LM/SL, we retrospectively identified 47 patients who had previously undergone WLE. Patient and tumor characteristics were collected and compared with followup data from clinic files. RESULTS: Median WLE surgical margins before LM/SL were 2.0 cm and most patients had extremity lesions. Eleven of the 47 patients (23%) had tumor-involved sentinel nodes, and 8 of these patients (73%) had a solitary nodal metastasis. With a median followup period of 36 months, 3 sentinel node-negative patients developed nodal recurrences. Two of these patients had positive sentinel nodes on pathology re-review and were not considered failures of the lymphatic mapping surgical procedure. The third patient developed in-transit metastases and delayed nodal recurrence. An additional patient, who had a primary tumor on the trunk, developed a nodal recurrence in the basin opposite that identified by lymphoscintigraphy. The overall error rate of the technique was 4 in 36 (11%). This included 2 pathology misdiagnoses (5.6%), 1 nodal recurrence associated with in-transit regional metastases (2.8%), and 1 lymphatic mapping error (2.8%). CONCLUSIONS: LM/SL can be cautiously performed in patients who have undergone previous WLE if the primary resection margin was no greater than 2.0 cm and the primary was not in a region of ambiguous drainage. Lymphatic mapping may be inaccurate when melanomas have been resected with large margins, especially if the wound was closed with rotation flaps, and when melanomas are on the head and neck or trunk regions.

Adult↗

PubMed1999

Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group.

OBJECTIVE: To evaluate the multicenter application of intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) for the management of early-stage melanoma. SUMMARY BACKGROUND DATA: The multidisciplinary technique of LM/SL/SCLND has been widely adopted, but not validated in a multicenter trial. The authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT) 5 years ago to evaluate the survival of patients with early-stage primary melanoma after wide excision alone versus wide excision plus LM/SL/SCLND. This study examined the accuracy of LM/SL/SCLND in the MSLT, using the experience of the organizing center (John Wayne Cancer Institute [JWCI]) as a standard for comparison. METHODS: Before entering patients into the randomization phase, each center in the MSLT was required to finish a 30-case learning phase with complete nuclear medicine, pathology, and surgical review. Selection of MSLT patients in the LM/SL/SCLND treatment arm was based on complete pathologic and surgical data. The comparison group of JWCI patients was selected using these criteria: primary cutaneous melanoma having a thickness > or =1 mm with a Clark level > or =III, or a thickness <1 mm with a Clark level > or =IV (MSLT criterion); LM/SL performed between June 1, 1985, and December 30, 1998; and patient not entered in the MSLT. The accuracy of LM/SL/SCLND was determined by comparing the rates of sentinel node (SN) identification and the incidence of SN metastases in the MSLT and JWCI groups. RESULTS: There were 551 patients in the MSLT group and 584 patients in the JWCI group. In both groups, LM performed with blue dye plus a radiocolloid was more successful (99.1 %) than LM performed with blue dye alone (95.2%) (p = 0.014). After a center had completed the 30-case learning phase, the success of SN identification in the MSLT group was independent of the center's case volume or experience in the MSLT. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.

Adolescent↗

PubMed1999

Gamma knife radiosurgery for metastatic melanoma: an analysis of survival, outcome, and complications.

OBJECTIVE: Although the mainstays for treatment of metastatic brain disease have been surgery and/or external beam radiation therapy, an increasing number of patients are being referred for stereotactic radiosurgery as the primary intervention for their intracranial pathological abnormalities. The lack of efficacy and cognitive and behavioral consequences of whole brain irradiation have prompted clinicians to select patients for alternative therapies. This study analyzes the effectiveness of Leksell gamma unit therapy for metastatic melanoma to the brain. METHODS: We present our experience with 59 Leksell gamma unit treatment sessions in 45 consecutive patients who presented with metastatic melanoma to the brain. Five of these procedures were performed as salvage therapy for patients who needed second radiosurgical treatment for new lesions that were remote from the previous targets and were not included in the overall analyses. RESULTS: The population included 78% male patients. The mean patient age was 53 years (age range, 24-80 yr). The mean time from diagnosis of primary melanoma to discovery of brain metastasis was 43 months (median, 27.5 mo; range, 1-180 mo). At the time of diagnosis of brain disease, 35.5% of the patients (16 of 45 patients) had neurological symptoms, 77.7% (35 of 45 patients) had known visceral metastases, and 11.1% (5 of 45 patients) had seizure disorders. Eighty-six percent of the lesions (80 of 93 lesions) were cortical, 12% (11 of 93 lesions) were cerebellar, 1% (1 of 93 lesions) were pontine, and 1% (1 of 93 lesions) were thalamic. Fifty-seven percent of the sessions (31 of 54 sessions) were performed for a single lesion, 24.1% (13 of 54 sessions) for two lesions, 9.2% (5 of 54 sessions) for three lesions, 7.4% (4 of 54 sessions) for four lesions, and 1.8% (1 of 54 sessions) for five lesions. The mean treatment volume was 5.6 cc, with a mean prescription of 21.6 Gy to the 56.0% mean isodose line. The median survival time of the patients in our population, using Kaplan-Meier curves, was 43 months from the time of diagnosis of primary melanoma (range, 3-180 mo) and 8 months (range, 1-20 mo) from the time of gamma knife treatment. Complications included seizures within 24 hours of the procedure in four patients, with transient nausea and vomiting in three patients, transient worsening of preprocedure paresis responsive to steroids in three patients, and increased confusion in one patient. All 45 patients were located for follow-up (mean follow-up duration, 1 yr). After gamma knife treatment, 78% of the patients (35 of 45 patients) experienced either improved or stable neurological symptomatology before death or at the time of the latest follow-up examination. There were 26 deaths (58%). The cause of death was determined to be neurological in only 2 of 45 patients (7.7%). Follow-up magnetic resonance images revealed a 97% local tumor control rate of gamma knife-treated lesions, with 28% radiographic disappearance (9 of 32 cases). Six patients developed new lesions remote from radiosurgical targets and underwent second procedures. CONCLUSION: Although metastatic melanoma to the brain continues to have a foreboding prognosis for long-term survival, gamma knife radiosurgery seems to be a relatively safe, noninvasive, palliative therapy, halting or reversing neurological progression in 77.8% of treated patients (35 of 45 patients). The survival rate matches or exceeds those previously reported for surgery and other forms of radiotherapy. Only 7.7% of the patients in our study population who died as a result of metastatic melanoma (2 of 26 patients) died as a result of neurological disease. The routine use of therapeutic level antiseizure medication is emphasized, considering the findings of our review.

Adult↗

PubMed1999

Stereotactic radiosurgery in the treatment of metastatic disease to the brain.

We review 190 consecutive patients with 434 metastatic tumors treated by gamma knife stereotactic radiosurgery, from August 1994 to February 1999. Median actuarial survival for all patients was 34 weeks. Factors correlated with significantly improved survival included controlled systemic disease and nonmelanoma histology. We found that no significant survival benefit could be discerned from adjuvant whole brain radiotherapy in this patient group. Survival was not statistically different for patients initially presenting with 1-4 metastases at initial treatment.

Brain Neoplasms↗

PubMed1999

Prognostic significance of occult metastases detected by sentinel lymphadenectomy and reverse transcriptase-polymerase chain reaction in early-stage melanoma patients.

PURPOSE: Detection of micrometastases in the regional tumor-draining lymph nodes is critical for accurate staging and prognosis in melanoma patients. We hypothesized that a multiple-mRNA marker (MM) reverse transcriptase-polymerase chain reaction (RT-PCR) assay would improve the detection of occult metastases in the sentinel node (SN), compared with hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC), and that MM expression is predictive of disease relapse. PATIENTS AND METHODS: Seventy-two consecutive patients with clinical early-stage melanoma underwent sentinel lymphadenectomy (SLND). Their SNs were serially sectioned and assessed for MAGE-3, MART-1, and tyrosinase mRNA expression by RT-PCR, in parallel with H&E staining and IHC, for melanoma metastases. MM expression in the SNs was correlated with H&E and IHC assay results, standard prognostic factors, and disease-free survival. RESULTS: In 17 patients with H&E- and/or IHC-positive SNs, 16 (94%) expressed two or more mRNA markers. Twenty (36%) of 55 patients with histopathologically negative SNs expressed two or more mRNA markers. By multivariate analysis, patients at increased risk of metastases to the SN had thicker lesions (P =.03), were 60 years of age or younger (P <.05), and/or were MM-positive (P <.001). Patients with histopathologically melanoma-free SNs who were MM-positive, compared with those who were positive for one or fewer mRNA markers, were at increased risk of recurrence (P =.02). Patients who were MM-positive with histopathologically proven metastases in the SN were at greatest risk of disease relapse (P =. 01). CONCLUSION: H&E staining and IHC underestimate the true incidence of melanoma metastases. MM expression in the SN more accurately reflects melanoma micrometastases and is also a more powerful predictor of disease relapse than are H&E staining and IHC alone.

Adult↗

PubMed1999

Advantages of concurrent biochemotherapy modified by decrescendo interleukin-2, granulocyte colony-stimulating factor, and tamoxifen for patients with metastatic melanoma.

PURPOSE: Concurrent biochemotherapy results in high response rates but also significant toxicity in patients with metastatic melanoma. We attempted to improve its efficacy and decrease its toxicity by using decrescendo dosing of interleukin-2 (IL-2), posttreatment granulocyte colony-stimulating factor (G-CSF), and low-dose tamoxifen. PATIENTS AND METHODS: Forty-five patients with poor prognosis metastatic melanoma were treated at a community hospital inpatient oncology unit affiliated with the John Wayne Cancer Institute (Santa Monica, CA) between July 1995 and September 1997. A 5-day modified concurrent biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo IL-2, interferon alfa-2b, and tamoxifen was repeated at 21-day intervals. G-CSF was administered beginning on day 6 for 7 to 10 days. RESULTS: The overall response rate was 57% (95% confidence interval, 42% to 72%), the complete response rate was 23%, and the partial response rate was 34%. Complete remissions were achieved in an additional 11% of patients by surgical resection of residual disease after biochemotherapy. The median time to progression was 6.3 months and the median duration of survival was 11.4 months. At a maximum follow-up of 36 months (range, 10 to 36 months), 32% of patients are alive and 14% remain free of disease. Decrescendo IL-2 dosing and administration of G-CSF seemed to reduce toxicity, length of hospital stay, and readmission rates. No patient required intensive care unit monitoring, and there were no treatment-related deaths. CONCLUSION: The data from this study indicate that the modified concurrent biochemotherapy regimen reduces the toxicity of concurrent biochemotherapy with no apparent decrease in response rate in patients with poor prognosis metastatic melanoma.

Adult↗

PubMed1999

Function of a minus-end-directed kinesin-like motor protein in mammalian cells.

CHO2 is a mammalian minus-end-directed kinesin-like motor protein present in interphase centrosomes/nuclei and mitotic spindle fibers/poles. Expression of HA- or GFP-tagged subfragments in transfected CHO cells revealed the presence of the nuclear localization site at the N-terminal tail. This domain becomes associated with spindle fibers during mitosis, indicating that the tail is capable of interaction with microtubules in vivo. While the central stalk diffusely distributes in the entire cytoplasm of cells, the motor domain co-localizes with microtubules throughout the cell cycle, which is eliminated by mutation of the ATP-binding consensus motif from GKT to AAA. Overexpression of the full-length CHO2 causes mitotic arrest and spindle abnormality. The effect of protein expression was first seen around the polar region where microtubule tended to be bundled together. A higher level of protein expression induces more elongated spindles which eventually become disorganized by loosing the structural integrity between microtubule bundles. Live cell observation demonstrated that GFP-labeled microtubule bundles underwent continuous changes in their relative position to one another through repeated attachment and detachment at one end; this results in the formation of irregular number of microtubule focal points in mitotic arrested cells. Thus the primary action of CHO2 appears to cross-link microtubules and move toward the minus-end direction to maintain association of the microtubule end at the pole. In contrast to the full-length of CHO2, overexpression of neither truncated nor mutant polypeptides resulted in significant effects on mitosis and mitotic spindles, suggesting that the function of CHO2 in mammalian cells may be redundant with other motor molecules during cell division.

Animals↗

PubMed1998

Prognostic implications of p53 overexpression in cutaneous melanoma from sun-exposed and nonexposed sites.

BACKGROUND: There is increasing evidence that mutations in the p53 tumor suppressor gene are among the most common genetic alterations in human malignancies. Because ultraviolet light can induce specific p53 mutations and is linked to the development of skin cancers, this study was done to determine the significance of p53 protein (p53p) overexpression in melanomas originating at different cutaneous sites varying in frequency of sunlight exposure. METHODS: Sixty-three paraffin embedded primary and metastatic melanoma biopsy specimens from 61 patients were deparaffinized and stained with the mouse monoclonal antibody DO-1 to wild-type and mutant p53p. Twenty-eight specimens were from primary tumors and 35 specimens were from lymph node, subcutaneous, or visceral metastases. The chi-square test was used to assess the significance of p53p overexpression, and the Cox proportional hazards model was used to estimate the impact of p53p overexpression on survival. RESULTS: Of the 61 patients studied, 37 had primary cutaneous melanomas arising on chronically sun-exposed head and neck sites, 12 patients on intermittently exposed extremity sites, and 12 patients on rarely exposed trunk sites. Thirteen of the 63 primary or metastatic specimens (21%) overexpressed p53p. Overexpression of p53p was not related to patient gender or age, anatomic site of the primary tumor, Clark level, or Breslow thickness. However, those patients with p53p positive primary tumors or metastases had significantly better survival than those determined to be negative for p53p overexpression (P = 0.045). The median survival was 152.4 months for p53p positive patients versus 55.7 months for p53p negative patients. The risk ratio of dying from melanoma was 0.32 for patients with tumor specimens overexpressing p53p. CONCLUSIONS: In this study, p53p overexpression was infrequent in paraffin embedded melanoma specimens and independent of the primary melanoma's anatomic site. Although p53p overexpression was not related to other prognostic features of primary or metastatic lesions, it was associated with a significantly improved survival in this group of melanoma patients.

Adult↗

PubMed1998

Kinetics of three lymphoscintigraphic agents in patients with cutaneous melanoma.

UNLABELLED: Although lymphoscintigraphy is commonly used for the preoperative evaluation of patients with cutaneous melanoma and for intraoperative identification of sentinel lymph nodes, there is no consensus regarding the most useful radiopharmaceuticals or imaging times. METHODS: Fifty-one consecutive patients with clinical American Joint Committee on Cancer Stage I or II melanoma were assigned to one of three groups of 17 for lymphoscintigraphy with one of three radiopharmaceuticals: 99mTc-albumin colloid (AC), 99mTc-human serum albumin (HSA) or 99mTc-sulfur colloid (SC). Colloidal agents were filtered through 0.2 microm filters. After injecting 18.5-30 MBq (500-800 microCi) of the radiopharmaceutical, dynamic monitoring over injection sites and node basins was performed to identify draining lymphatic channels and sentinel nodes. In addition, static digital and analog images were acquired from the injection site and draining node basins immediately after injection and at 30 min (early) and 2 to 4 hr (delayed) after injection. Dynamic and static images were analyzed to determine transit times to the sentinel node, the number of nodes visualized in early and delayed images, the quality of lymph node and lymph channel visualization, the sentinel-to-nonsentinel uptake ratios and the washout rates from injection sites. RESULTS: Early images with all three agents provided reliable identification of sentinel lymph nodes. Technetium-99m-HSA demonstrated faster washout rates from injection sites and better definition of lymph channels than either particulate agent, whereas particulate agents were retained longer in nodes and demonstrated more nodes in delayed images than in early images. All agents demonstrated lymph channels better in early images than in delayed images. In general, variations between patients exceeded differences between agents. Sentinel nodes could not be distinguished reliably from nonsentinel nodes in delayed images alone. CONCLUSION: All three agents are acceptable for cutaneous lymphoscintigraphy, but reliable identification of sentinel nodes and their afferent lymph channels requires early imaging. Delayed imaging or localization alone is unreliable and may lead to incorrect identification of the sentinel node.

Female↗

PubMed1997

Endothelial-selectin ligands sialyl Lewis(x) and sialyl Lewis(a) are differentiation antigens immunogenic in human melanoma.

BACKGROUND: Sialyl Lewis(x) (sLe(x)) and sialyl Lewis(a) (sLe(a)), the endothelial-selectin ligands involved in extravasation of neutrophils and carcinomas, have been identified in human melanoma. This study explored the following issue: If these ligands are immunogenic tumor-differentiation antigens, they would be potential targets for immunotherapy because of their putative roles in extravasation and metastasis. METHODS: Using a cell-suspension enzyme-linked immunosorbent assay (ELISA), the expression of sLe(x) and sLe(a) on the surface of normal melanocytes, melanoma cells from biopsies, and cell lines (M10-v, M24, and M101) constituting melanoma cell vaccine (MCV) were quantitated. Melanoma patients were immunized with the MCV expressing these antigens. Sera of normal individuals, sera of patients, and sera that adsorbed to sLe(x) and sLe(a) were titrated for anti-sLe antibodies by ELISA to verify the immunogenicity of the ligands. RESULTS: The normal melanocytes did not express sLe(x) and poorly expressed sLe(a). Melanoma cells from tumor biopsies and MCV lines expressed both sLe(x) and sLe(a). Sialyl Le(x) was associated with glycoprotein(s) in M10-v, and sLe(a) occurred as a glycolipid moiety in M24. MCV recipients developed high titers for immunoglobulin (Ig)M but not IgG to both ligands. IgM titers to these ligands were low in normal subjects. In some of the preimmune sera of patients, the titers were threefold above normal. Six of 13 MCV recipients developed at least a twofold increase in anti-sLe titers above preimmune level after the second or third immunization. Adsorption studies suggested that both ligands were immunogenic. CONCLUSIONS: The melanoma-associated sLe(x) and sLe(a) are immunogenic neoplasm-differentiation antigens and are therefore potential targets for passive and active specific immunotherapy in the treatment of melanoma.

Animals↗

PubMed1997

Intraoperative lymphatic mapping for early-stage melanoma of the head and neck.

BACKGROUND: We previously reported dye-directed intraoperative lymphatic mapping and selective sentinel lymphadenectomy for primary cutaneous melanomas draining to the neck lymph nodes. In this study we determined whether combining the dye with a radiopharmaceutical agent would enhance our rate of sentinel node detection. METHODS: One hundred seventeen patients with primary cutaneous melanomas of the upper chest and head and neck underwent preoperative cutaneous lymphoscintigraphy to confirm lymphatic drainage to neck nodes, followed by intraoperative lymphatic mapping and sentinel lymphadenectomy. In 94 cases, isosulfan blue dye was injected at the primary site; in the remaining 23 cases, a 1:3 mixture of radiopharmaceutical and dye was injected, and a hand-held probe was used to determine the radioactive counts. RESULTS: Preoperative cutaneous lymphoscintigraphy identified 129 drainage basins; 12 patients (10%) had dual-basin drainage. During intraoperative lymphatic mapping and sentinel lymphadenectomy, 183 sentinel nodes were identified and excised from 120 basins (1.5 nodes/basin). The blue dye alone identified sentinel nodes in 93 of 101 basins (92%). The probe identified sentinel nodes in 28 of 28 basins, only one of which failed to reveal blue-staining sentinel nodes; thus, the probe plus dye identified sentinel nodes in 27 of 28 basins (96%). Histopathologic analysis revealed metastasis in sentinel nodes from 11 patients (12%) who underwent sentinel lymphadenectomy with blue dye alone and in 3 patients (13%) who underwent sentinel lymphadenectomy with dye plus probe. There were no same-basin recurrences over a mean follow-up of 46 months (range 1 to 125). CONCLUSIONS: Selective sentinel lymphadenectomy is a highly accurate method of staging the regional nodes in patients with primary tumors of the head and neck. Although we initially demonstrated the utility of this technique with blue dye alone, our results now suggest that the combination of dye and radiopharmaceutical may be a more sensitive method to detect sentinel nodes.

Coloring Agents↗

PubMed1997

Expression of a minus-end-directed motor protein induces Sf9 cells to form axon-like processes with uniform microtubule polarity orientation.

Neurons extend two types of processes with distinct morphologies and patterns of microtubule polarity orientation. Axons are thin cylindrical processes containing microtubules that are uniformly oriented with their plus-ends-distal to the cell body while dendrites are stout tapering processes that contain nonuniformly oriented microtubules. We have proposed that these distinct microtubule patterns are established by molecular motors that transport microtubules into each type of process with the appropriate orientation. To test the feasibility of this proposal, we have embarked on a series of studies involving the expression of vertebrate motors in insect Sf9 cells. We previously focused on a kinesin-related protein termed CHO1/MKLP1, which localizes to the midzone of the mitotic spindle, and which has been shown to have the appropriate properties to transport microtubules of opposite orientation relative to one another. Expression of a fragment of CHO1/MKLP1 containing its motor domain induces Sf9 cells to extend processes with a stout tapering morphology and a nonuniform microtubule polarity pattern similar to dendrites. Here we focus on a minus-end-directed kinesin-related motor protein termed CHO2, which localizes to the non-overlapping regions of the mitotic spindle, and which has been shown to have the appropriate properties to transport microtubules with plus-ends-leading. Sf9 cells induced to express a fragment of CHO2 containing its motor domain extend processes with a long cylindrical morphology and a uniformly plus-end-distal microtubule polarity pattern similar to axons. These results show that motor proteins have the capacity to organize distinct patterns of microtubule polarity orientation during process outgrowth, and that these patterns are intimately related to the unique morphological characteristics of the processes. Moreover, mutation of three amino acids corresponding to the ATP binding site necessary for motor function suppresses the capacity of the CHO2 fragment to induce process formation and microtubule reorganization, indicating that at least in the case of CHO2, the transport properties of the motor are essential for it to elicit these effects.

Animals↗

PubMed1997

The role of lymphoscintigraphy and sentinel node mapping in assessing patient risk in melanoma.

The presence or absence of regional nodal metastases is one of the most important prognostic factors for the survival of patients with primary cutaneous melanoma. The successful outcome of treatment is thus critically dependent on accurate staging of the primary tumor and detection of any occult micrometastases in the regional lymph nodes draining that tumor. Preoperative cutaneous lymphoscintigraphy to identify and visualize the lymphatic drainage patterns from primary tumors and intraoperative lymphatic mapping to identify the first ("sentinel") lymph node in direct communication with the primary tumor are valuable diagnostic tools. These techniques have greatly enhanced the oncologist's ability to identify occult lymph node metastases and to select patients with cutaneous melanoma who may potentially benefit from adjuvant therapy with recombinant interferon alpha-2b.

Algorithms↗

PubMed1996

Interleukin 4 inhibits hepatocyte growth factor-induced invasion and migration of colon carcinomas.

Hepatocyte growth factor (HGF) is known to have a number of biological properties including promoting tumor progression of human carcinomas. Metastasis involves a number of events that are attributed to induction by paracrine factors such as HGF. Identification of natural inhibitors of these events would allow better control of tumor progression. Recently we demonstrated that interleukin 4 (IL-4) can regulate proliferation of various human carcinoma cell lines. In the present study, we used established human colon carcinoma cell lines and primary colon carcinoma cell cultures to determine if IL-4 could regulate HGF-induced cell proliferation and other events of tumor progression such as MMP (matrix metalloproteinases)-1, -2, and -9 production, cell migration and cell-matrix invasive activity. All colon carcinoma cell lines expressed HGF and IL-4 receptors. IL-4 significantly inhibited HGF-induced proliferation of one cell line. Cell-matrix invasion was significantly enhanced by HGF (0.1-10 ng/ml); IL-4 (1-10 U/ml) significantly inhibited HGF-induced invasion in a dose-dependent manner. IL-4 also inhibited HGF-induced cell-matrix invasion of metastatic colon carcinoma cells and HGF-induced cell migration. HGF enhanced MMP-1, -2, and -9 production by cell lines. This effect could be inhibited by IL-4. These findings indicate that IL-4 is a potent inhibitor of HGF-induced invasion and metastasis-related functions of human colon carcinoma cells.

Antigens, CD↗

PubMed1996

Surgical resection for melanoma metastatic to the gastrointestinal tract.

OBJECTIVE: To evaluate the role of surgery in the survival of patients with melanoma metastatic to the gastrointestinal (GI) tract. DESIGN: Retrospective review. SETTING: Tertiary cancer center. PATIENTS: One hundred twenty-four potential surgical candidates with metastatic melanoma in the stomach, small intestine, colon, or rectum. MAIN OUTCOME MEASURES: Operative morbidity and mortality, relief of presenting symptoms, and median and 5-year survival. RESULTS: The median disease-free interval prior to diagnosis of GI tract metastasis was 23.2 months (range, 1-154 months). Patients typically presented with crampy abdominal pain, symptomatic mass, and/or occult GI tract blood loss. Of the 124 patients, 69(55%) underwent surgical exploration of the abdomen, 46 (66%) had curative resection, and 23 (34%) had a palliative procedure. There was only 1 operative death and 1 major operative complication; 67 (97%) of 69 surgical patients experienced postoperative relief of their presenting GI tract symptoms. The median survival in patients undergoing curative resection was 48.9 months, compared with only 5.4 months and 5.7 months in those undergoing palliative procedures and nonsurgical interventions, respectively. By multivariate analysis, the 2 most important prognostic factors for long-term survival were complete resection of GI tract metastases and the GI tract as the initial site of distant metastases. CONCLUSIONS: Almost all patients with melanoma and GI tract metastases can have palliation of symptoms by surgical intervention with minimal morbidity and mortality. The high 5-year survival rate associated with complete surgical resection of GI tract metastases indicates that surgery should be strongly considered for this subgroup of patients with melanoma and distant metastatic disease.

Female↗

PubMed1996

Nonpalpable versus palpable invasive breast tumors treated with breast-conserving surgical management.

Most mammographically detected breast cancers are small, nonpalpable malignancies that should be amenable to cure by definitive breast-conserving therapy (BCT) consisting of tumor excision and postoperative radiation. We examined this hypothesis by retrospectively comparing the incidence of local recurrence and the rate of survival in breast cancer patients undergoing BCT for nonpalpable versus palpable lesions. Between 1982 and 1991, 345 patients at the John Wayne Cancer Institute, a large referral center for breast diseases, underwent BCT for invasive ductal and/or invasive lobular breast carcinomas: 120 (35%) had nonpalpable lesions detected by mammography (MG group), and 225 (65%) had palpable lesions detected by physical exam (PE group). The clinical and pathologic tumor status and the clinical outcome were recorded in each case. Median tumor size was significantly larger in PE than MG patients (2 cm versus 1 cm, P < 0.001). Only 29 percent of MG patients were premenopausal, compared with 51 percent of PE patients (P < 0.05). Axillary node involvement was more frequent in PE than MG patients (46% versus 19%, P < 0.01). Over a median follow-up of 58 months, local recurrence rates were 8 per cent for both MG and PE patients. In both groups, the incidence of local recurrence increased significantly when tumor was found in the margins of the resected breast specimen. In the MG group, the risk of local recurrence was significantly higher in premenopausal patients (P < 0.05). Survival was similar in both groups. The rate of local recurrence after BCT is the same for nonpalpable and palpable breast tumors. However, nonpalpable lesions have a lower rate of regional node metastases, which may improve survival. Both local recurrence and metastases seem to be related to tumor size. Tumor-free operative margins are the best predictor of local control.

Adult↗

PubMed1995

Characterization of a minus end-directed kinesin-like motor protein from cultured mammalian cells.

Using the CHO2 monoclonal antibody raised against CHO spindles (Sellitto, C., M. Kimble, and R. Kuriyama. 1992. Cell Motil. Cytoskeleton. 22:7-24) we identified a 66-kD protein located at the interphase centrosome and mitotic spindle. Isolated cDNAs for the antigen encode a 622-amino acid polypeptide. Sequence analysis revealed the presence of 340-amino acid residues in the COOH terminus, which is homologous to the motor domain conserved among other members of the kinesin superfamily. The protein is composed of a central alpha-helical portion with globular domains at both NH2 and COOH termini, and the epitope to the monoclonal antibody resides in the central alpha-helical stalk. A series of deletion constructs were created for in vitro analysis of microtubule interactions. While the microtubule binding and bundling activities require both the presence of the COOH terminus and the alpha-helical domain, the NH2-terminal half of the antigen lacked the ability to interact with microtubules. The full-length as well as deleted proteins consisting of the COOH-terminal motor and the central alpha-helical stalk supported microtubule gliding, with velocity ranging from 1.0 to 8.4 microns/minute. The speed of microtubule movement decreased with decreasing lengths of the central stalk attached to the COOH-terminal motor. The microtubules moved with their plus end leading, indicating that the antigen is a minus end-directed motor. The CHO2 sequence shows 86% identify to HSET, a gene located at the centromeric end of the human MHC region in chromosome 6 (Ando, A., Y. Y. Kikuti, H. Kawata, N. Okamoto, T. Imai, T. Eki, K. Yokoyama, E. Soeda, T. Ikemura, K. Abe, and H. Inoko. 1994. Immunogenetics. 39:194-200), indicating that HSET might represent a human homologue of the CHO2 antigen.

Amino Acid Sequence↗