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S D Nathanson

Publications and source records attributed to S D Nathanson.

At least 19 recordsLinked to original sources

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells.

Numerous immunohistochemical stains have been employed to detect metastatic melanoma in sentinel lymph node (SLN) biopsies. HMB-45 is considered by some as a specific tool to detect early metastatic melanoma (1). Occasionally, one or two isolated HMB-45-positive cells may cause complications in diagnostic interpretation. The goal of this study was to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare its staining with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining was performed on (Group A) 15 histologically negative SLNs excised from patients with malignant melanoma (MM) and on (Group B) 15 histologically negative SLNs excised from patients with breast carcinoma (BC). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all Group B SLNs after blocking endogenous biotins. Electron-microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in 6 of 15 SLNs removed for MM; 8 of 15 for BC; and 3 of 5 cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in 6 of 8 positive SLNs from Group B. Anti-Melan A antibody was negative in all SLNs of group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for the detection of micro-metastasis of MM and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.

Antigens, Neoplasm↗

Pathways of lymphatic drainage from the breast.

BACKGROUND: The current standard for obtaining accurate sentinel lymph node (SLN) mapping is intraparenchymal lymphophilic dye/radiocolloid injection close to the breast tumor. We hypothesized that common lymphatic trunks drain both a large volume of breast parenchyma and skin and that intradermal or intraparenchymal routes flow to the same axillary node. METHODS: 99mTc-labeled filtered sulfur colloid was injected intradermally directly over the breast tumor in 119 patients. Blue dye was injected intraparenchymally in the same quadrant as the primary tumor (concordant quadrant) in 66 and in a discordant quadrant in 53 patients. During axillary exploration, both blue and gamma-emitting (hot) nodes were found. End points were SLNs that were hot and blue, either the same node or different nodes. RESULTS: In 62 (93.9%) of 66 of concordant quadrant and in 49 (92.5%) of 53 of discordant quadrant patients, the same SLN was both hot and blue (P = .99; Fisher's exact test). In eight cases in which two distinct nodes were blue and not hot and hot but not blue, the lymph nodes were very close to each other. CONCLUSIONS: The dermal and parenchymal lymphatics of the breast seemed to drain to the same axillary lymph nodes. Lymph from the entire breast seemed to drain through a small number of lymphatic trunks to one or two lymph nodes.

Aged↗

Microvessels that predict axillary lymph node metastases in patients with breast cancer.

HYPOTHESIS: The density of vasoactive endothelial growth factor receptor 3-immunostained microvessels in primary breast cancers correlates with the incidence of axillary lymph node metastasis. DESIGN: Breast cancer microvessel clusters ("hot spots") were sequentially immunostained for factor VIII, type IV collagen, and vasoactive endothelial growth factor receptor 3. Microvessels were counted under light microscopy at a magnification of x 200. Axillary lymph nodes were evaluated for metastases by light microscopy. SETTING: A multidisciplinary breast cancer clinic and laboratory. PATIENTS: Sixty patients with T2 breast cancers treated by lumpectomy (or mastectomy) and axillary lymphadenectomy. MAIN OUTCOME MEASURES: Putative lymphatic microvessel density compared with axillary metastases. RESULTS: There were 16% (SE, 1.4%) vs 4% (SE, 0.8%) vasoactive endothelial growth factor receptor 3-immunostained microvessels (P<.001), 38% (SE, 3.9%) vs 65% (SE, 3.1%) type IV collagen-immunostained microvessels (P<.001), and 46% (SE, 4.1%) vs 31% (SE, 3.2%) unstained microvessels (P = .004) in node-positive vs node-negative patients, respectively. A fitted logistic model based on the relative percentage of putative lymphatic microvessels to blood microvessels correctly predicted that 23 (96%) of 24 patients would have a low risk and that 26 (96%) of 27 patients would have a high risk of lymph node metastases. Six (67%) of 9 patients predicted to have an intermediate risk had lymph node metastases. CONCLUSION: The odds of a patient with breast cancer having axillary lymph node metastasis increased substantially as the proportion of putative lymphatic microvessels increased and the relative proportion of blood microvessels in angiogenic hot spots decreased (log likelihood = 14.6; chi2 = 53.4; P<.001; area under the receiver operation characteristic curve = 0.97).

Breast Neoplasms↗

Comparison of mammographically guided breast biopsy techniques.

OBJECTIVE: To determine which mammographically guided breast biopsy technique is the most efficient in making a diagnosis in women with suspicious mammograms. SUMMARY BACKGROUND DATA: Mammographically guided biopsy techniques include stereotactic 14-gauge core-needle biopsy (SC bx), stereotactic 11-gauge suction-assisted core biopsy (Mammotome [Mbx]), stereotactic coring excisional biopsy (Advanced Breast Biopsy Instrument [ABBI]), and wire-localized biopsy (WL bx). Controversy exists over which technique is best. METHODS: All patients undergoing any one of these biopsy methods over a 15-month period were reviewed, totaling 245 SC bx, 107 Mbx, 104 ABBI, and 520 WL bx. Information obtained included technical success, pathology, discordant pathology, and need for open biopsy. RESULTS: Technical success was achieved in 94.3% of SC bx, 96.4% of Mbx, 92.5% of ABBI, and 98.7% of WL bx. The sensitivity and specificity were 87.5% and 98.6% for SC bx, 87.5% and 100% for Mbx, and 100% and 100% for ABBI. Discordant results or need for a repeat biopsy occurred in 25.7% of SC bx, 23.2% of Mbx, and 7.5% of ABBI biopsies. In 63.6% of ABBI and 50.9% of WL bx, positive margins required reexcision; of the cases with positive margins, 71.4% of ABBI and 70.4% of WL bx had residual tumor in the definitive treatment specimen. CONCLUSION: Although sensitivities and specificities of SC bx and Mbx are good, 20% to 25% of patients will require an open biopsy because a definitive diagnosis could not be reached. This does not occur with the ABBI excisional biopsy specimen. The positive margin rates and residual tumor rates are comparable between the ABBI and WL bx. The ABBI avoids operating room and reexcision costs; therefore, in appropriately selected patients, this appears to be the most efficient method of biopsy.

Biopsy↗

Racial differences in the presentation and surgical management of breast cancer.

BACKGROUND: African American women are seen with more advanced breast cancers, are less likely to be treated with breast-conserving surgery, and generally have poorer prognoses than white women. There are a myriad of potential causes for these phenomena. The purpose of this study was to measure racial differences in the surgical treatment of breast cancer among women with comparable health care access and delivery. METHODS: The Breast Cancer Registry of the Department of Surgery at Henry Ford Hospital was accessed for all patients between January 1, 1990, and December 31, 1997 for whom data on race, tumor characteristics, stage, and treatment specifics were available. Socioeconomic information was collected with use of 1990 census block data. Proportions of women who received each treatment were compared for African Americans and whites with use of the relative risk (RR) and 95% confidence intervals (CI). We used multiple logistic regression to obtain estimates of the relative risk, controlling for potential confounding factors. RESULTS: Of the 1699 patients in the database, 1250 had sufficient information for analysis. A total of 8.7% of African American women were diagnosed with late-stage disease (i.e., stage III or IV) compared with 7.9% of whites. Nevertheless, African American women had a lower frequency of stage I disease (30.5% vs 36.2%) and a higher frequency of stage II disease (36.8% vs 31.4%). Overall and adjusted risk estimates for age, tumor stage, marital status, median income, and type of insurance revealed no substantive or statistically significant differences between African American and white patients. The adjusted RR for local excision was 1.39 (95% CI 0.78 to 2.49), for lumpectomy and axillary dissection RR 0.92 (95% CI 0.66 to 1.29), for simple mastectomy RR 0.84 (95% CI 0.41 to 1.72), and for modified radical mastectomy RR 1.00 (95% CI 0.73 to 1.36). CONCLUSIONS: In this setting of equal access to health care, African American women still have higher frequencies of stage II disease, although the frequencies for late-stage disease are similar. Nevertheless, no surgical differences were found in this population, even after the effects of socioeconomic indicators and stage at diagnosis were controlled for Survival differences between African American and white women are unlikely to be explained by differences in treatment.

Aged↗

A new BRCA1 mutation in a Filipino woman with a family history of breast and ovarian cancer.

Mutation of the BRCA1 gene in well-defined breast cancer families has been associated with an 87% lifetime risk for breast cancer and a 44% risk for ovarian cancer. Recent data indicate that the risk associated with these mutations is considerably lower, although still far greater than the risk for disease in the rest of the population. Approximately 81% of the mutations that have been identified have been frameshift (71%) or nonsense (10%) mutations, and either may result in a truncated protein. The protein truncation test (PTT) is often used to screen patients at high risk, because sequencing of this large (100 kb) gene with its 22 coding exons is an arduous task. The PTT was used to analyze genomic DNA and RNA from the peripheral blood of a 31-year-old Filipino woman with a poorly differentiated, stage 2A breast carcinoma and a family history of breast-ovarian cancer. PTT identified the wild-type protein fragment and an additional truncated protein fragment in the patient's sample. Subsequent direct sequencing of the appropriate coding region revealed a point mutation in exon 11 at nucleotide 2178, resulting in a C > T transition that caused a termination (stop codon) in amino acid 687. To our knowledge, this is the first report of mutation of the BRCA1 gene in a Filipino family, and this in-frame stop-codon mutation has not been reported previously.

Adult↗

Multidisciplinary breast cancer clinics. Do they work?

BACKGROUND: In an attempt to improve the care they provide for their patients with breast cancer, the authors' institution developed a multidisciplinary breast cancer clinic (MDBCC) to offer "one-stop shopping" consultation and support for newly diagnosed breast cancer patients. METHODS: One hundred sixty-two patients, the control group for this study, were evaluated at Henry Ford Hospital during the year prior to the opening of the MDBCC. These patients, who were referred in the traditional sequential consultation manner, were compared with the first 177 patients seen during the first year of the clinic's operation. Retrospective chart reviews were conducted to assess treatment timeliness, and anonymous questionnaires were used to assess patient satisfaction. RESULTS: The authors found that the MDBCC increased patient satisfaction by encouraging involvement of patients' families and friends and by helping patients make treatment decisions (P < 0.001). The time between diagnosis and the initiation of treatment was also significantly decreased (42.2 days vs. 29.6 days; P < 0.0008). CONCLUSIONS: Although planning and operating a multidisciplinary clinic is not a new venture, to the best of the authors' knowledge, they have provided the first report demonstrating the benefits described above.

Breast Neoplasms↗

Lymphatic diameters and radionuclide clearance in a murine melanoma model.

OBJECTIVES: To determine the clearance of a radionuclide from various sizes of footpad melanomas via lymphatics and to measure the diameters of these vessels. DESIGN: Nonrandomized animal study. SETTING: A hospital research laboratory. SUBJECTS: C57BL/6 mice. INTERVENTIONS: Female mice were injected in the right rear footpad with B16 F10 cells that were allowed to grow to either 1, 2, 3, 4, or 5 mm in anteroposterior diameter. Clearance from feet with or without tumors of injected technetium Tc 99m human serum albumin (99mTcHSA) was assessed for 200 minutes. Calf lymphatic diameters were measured using aniline blue dye. RESULTS: The clearance of the injected 99mTcHSA from mouse footpads without tumors was 1.26 +/- 0.18 x 10(-4) mL/min x cm3 of tissue. Clearance increased 2.24-fold to 2.82 +/- 0.12 x 10(-4) mL/min x cm3 of tissue from 1-mm tumors and to 6.20 +/- 0.08, 6.11 +/- 0.13, 6.91 +/- 0.58, and 7.23 +/- 0.48 x 10(-4) mL/min x cm3 of tissue from 2-, 3-, 4-, and 5-mm tumors, respectively (P < .05). Calf lymphatic diameters increased from 75.41 +/- 9.72 microns in naive nontumor-bearing mice to 93.51 +/- 7.12, 111.61 +/- 27.07, 126.69 +/- 25.20, 124.43 +/- 24.75, and 127.44 +/- 25.35 microns in mice bearing 1-, 2-, 3-, 4-, and 5-mm tumors, respectively (P < .01). CONCLUSIONS: There was a size-dependent, direct correlation between increasing tumor size in the footpad and increasing diameter of lymphatics draining the footpad. Clearance of injected 99mTcHSA from these tumors also exhibited a similar positive correlation with tumor size.

Animals↗

Sentinel lymph node uptake of two different technetium-labeled radiocolloids,.

BACKGROUND: The study was designed to compare the uptake of technetium-99m-labeled human serum albumin ([99mTc]HSA) and 99mtechnetium-labeled sulfur colloid ([99mTc]SC) in the sentinel lymph nodes (SLNs). METHODS: Radiocolloid levels in the SLN, femoral lymph node (FLN), ischial lymph node (ILN), spleen (SP), and right rear footpad (RRF) were quantitated over a period of 240 min after injection of [99mTc]SC or [99mTc]HSA into the rear footpad of C57 BL/6 mice. RESULTS: There was a significantly greater (p < 0.001) radioactive count in SLNs after [99mTc]SC (mean cpm 211,084.8) compared to [99mTc]HSA (mean cpm 115,640.8). In contrast, the counts in the FLNs were higher after [99mTc]HSA (mean cpm 11,333.4) than after [99mTc]SC injection (mean cpm 5,065.5). The percent uptake in the SP was higher after [99mTc]HSA than after [99mTc]SC injection. CONCLUSIONS: [99mTc]SC is rapidly and efficiently taken up by lymphatics at the primary injection site, is significantly retained in the SLN, and flows slowly to the next echelon node (FLN or ILN) and to the systemic circulation (SP). [99mTc]HSA tends to accumulate less efficiently in the SLN and to disperse more rapidly to the next echelon nodes and to the systemic circulation. By extrapolation, [99mTc]SC is likely to be a better radiocolloid for the intraoperative detection of SLNs.

Animals↗

Sentinel lymph node metastasis in experimental melanoma: relationships among primary tumor size, lymphatic vessel diameter and 99mTc-labeled human serum albumin clearance.

BACKGROUND: This study was designed to investigate the relationships among primary tumor size, lymphatic vessel diameters, the incidence of sentinel lymph node (SLN) metastasis and lymphatic clearance from murine footpad melanomas. METHODS: Lymphatic clearance (LC) of [99mTc]HSA from the middle of the footpad of syngeneic C57BL/6 mice, with or without primary melanomas (sizes varying from 1 to 5 mm in anteroposterior diameter), was quantitated using a gamma scintillation detection system. Lymphatic vessel diameters (LD) were measured after injection of aniline blue dye into footpad tumors. The incidence of SLN, femoral lymph node (FLN), and lung metastases was recorded. RESULTS: Metastasis to SLNs increased as tumor growth progressed (r = 0.976, p = 0.001), and there was a correlation between tumor size and both FLN (p = 0.041) and lung (p = 0.055) metastases. There was also a correlation between lymph node metastasis and LC (r = 0.83, p = 0.04) and LD (r = 0.84, p = 0.04). CONCLUSIONS: These studies support the hypothesis that lymph flow and LD is increased in experimental murine melanomas and this relates to both primary tumor size and to lymphatic and hematogenous metastasis.

Aniline Compounds↗

Rates of flow of technetium 99m--labeled human serum albumin from peripheral injection sites to sentinel lymph nodes.

BACKGROUND: The new technique of sentinel lymphadenectomy for cutaneous melanoma provided us with a unique opportunity to quantitate the rates of lymphatic flow in afferent lymphatics. METHODS: Seventeen melanoma patients underwent preoperative lymphoscintigraphy with technetium 99m-human serum albumin (HSA). The time and distance between the injection site and the sentinel lymph node (LN) were recorded. By comparison, lymphatic flow rates between footpad, popliteal LN, femoral LN, and systemic blood were measured in 60 female mice (C57BL/6) after footpad injection of 99mTc-HSA. RESULTS: The rate of lymphatic flow to 14 axillary, four inguinal, one popliteal, and one parotid sentinel LNs averaged 10.4 +/- 7.3 cm/min. In contrast, the lymphatic flow rate between the footpad and the popliteal LN in mice (analogous to the sentinel LN in human beings) averaged 1.33 +/- 0.52 cm/min. There was a marked delay in the passage of radionuclide through the popliteal LN with consequent slowing of the rate of flow between the popliteal and femoral LNs to 0.22 cm/min. CONCLUSION: Lymphatic flow to the sentinel LN occurs rapidly from both human skin and murine footpads. This information might be helpful in planning the timing of the incision after vital blue dye injection for identifying the sentinel LN.

Animals↗

Lack of correlation between flow cytometric and immunohistologic proliferation measurements of tumors.

We compared different means of assaying tumor proliferative activity by either flow cytometric or immunohistologic methods in formalin-fixed, paraffin-embedded blocks. A series of 84 Dukes' stage B colorectal carcinomas were examined to identify high-risk patients who may potentially benefit from adjuvant therapy. Flow cytometric analysis was performed by a modified Hedley method with a combined S+G2/M phase proliferative fraction calculated by means of a rectangular model after debris subtraction. Immunohistologic tumor proliferative activity was analyzed by means of serial step sections from the same blocks used for flow cytometric examination with antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1). Mean with standard deviation and (range) tumor proliferative activity measurements were: flow cytometric analysis: proliferative fraction = 14.8% +/- 5.3 (5-27%), PCNA = 43.2% +/- 21.2 (4-90%), and MIB-1 = 16.2% +/- 10.8 (2-47%). No correlation was found between flow cytometric proliferative fraction and immunohistologic tumor proliferation measurement or between PCNA and MIB-1 staining indices. Lack of correlation between flow cytometric and immunohistologic findings may be related to the use of archival formalin-fixed paraffin-embedded tissue for flow cytometric evaluation, with resultant increased debris and decreased accuracy of cell cycle calculations. Discordance between PCNA and MIB-1 may reflect inherent problems with anti-PCNA antibody staining of formalin-fixed tissues whereby anti-PCNA clone PC-10 detects non-replicon associated PCNA in formalin-fixed tissues. Prospective studies using fresh tissue with two-color multiparameter flow cytometric analysis and histogram-dependent background fitting may help to clarify the relationship between findings of tumor proliferation as analyzed by flow cytometric and by immunohistologic techniques.

Adenocarcinoma↗

Relationship among p53, stage, and prognosis of large bowel cancer.

PURPOSE: We designed a study to determine whether increases in p53 protein in primary carcinomas of the colon or rectum correlate with overall survival. Mutations of the tumor suppressor gene p53 are detectable by immunocytochemical methods in colorectal cancers because of accumulation of nuclear p53 protein. METHODS: IgG1 monoclonal antibody to human p53 protein (PAb 1801) was used to detect p53 in formalin-fixed, paraffin-embedded archival tumors resected from 84 patients with tumor limited to the bowel wall. A multivariate analysis was performed using five prognostic pathobiologic variables compared with the level of staining of the p53 product. RESULTS: Nuclear p53 protein was observed in 52 (62 percent) of 84 colorectal cancer patients with Stage T2 or T3, N0, M0 disease. Patients with strong expression (3+ and 4+) of p53 appeared to die from their disease sooner than those with weak expression (1+ and 2+), although this was not statistically significant (P > 0.59). Thirty-two patients did not express nuclear p53 by immunocytochemical methods. When these patients were analyzed in combination with the strong p53 expressors, the trend toward decreased survival increased (P > 0.15). CONCLUSIONS: This data suggest that lack of p53 expression may also predict an adverse outcome in colorectal cancer. However, before the immunocytochemical method can be used clinically as a prognostic indicator, the colorectal cancer patients with zero expression should be studied further to clarify the functional status of p53 in their tumors.

Adenocarcinoma↗

Interstitial fluid pressure in breast cancer, benign breast conditions, and breast parenchyma.

BACKGROUND: Interstitial fluid pressure (IFP) in rodent malignant tumors is reportedly much higher than in surrounding normal tissue. We hypothesized the same may be true in human invasive breast tumors. METHODS: We measured IFP in the operating room in 25 patients undergoing excision breast biopsy under local anesthetic for diagnostic purposes. RESULTS: In patients with invasive ductal carcinomas IFP was 29 +/- 3 (SE) mm Hg, compared with -0.3 +/- 0.1 mm Hg in those with normal breast parenchyma (p < 0.001), 3.6 +/- 0.8 mm Hg in those with benign tumors (p < 0.003), -0.3 +/- 0.2 mm Hg in those with noninvasive carcinomas (p = 0.034), and 0.4 +/- 0.4 mm Hg in those with other benign breast conditions (p = 0.002). There was a direct correlation between IFP and tumor size (R2 = 0.3977; p = 0.021). No correlation was found between IFP and nuclear grade, angiolymphatic invasion, systemic blood pressure, metastasis to lymph nodes, or estrogen and progesterone receptors. CONCLUSIONS: IFP measurements may facilitate radiographic or ultrasound localization of small or nonpalpable malignant tumors in those patients undergoing needle aspiration cytology or stereotactic core needle biopsy.

Adult↗

Hematomas following excisional breast biopsies for invasive breast carcinoma: the influence of deep suture approximation of breast parenchyma.

The controversy over whether breast parenchyma should be approximated by suture after excisional biopsy is largely unresolved. The major debate is whether suture closure will decrease the incidence of hematomas and perhaps adversely alter the contour of the breast. To focus on the first question, we analyzed 162 patients undergoing mastectomy for breast cancer at Henry Ford Hospital between July 1988 and August 1992. All patients had previous excisional biopsies of breast lumps for diagnostic purposes. The cases were divided into two major groups depending on the placement or lack thereof of deep sutures in breast parenchyma. Of the total number of patients, 105 had deep suture approximation of breast parenchyma, whereas 57 did not. The biopsies were performed by 17 surgeons, although 72 per cent were done by four surgeons. Most of the surgeons varied their technique sporadically, but the number of cases most handled individually were too small for statistical analysis. Macroscopic and microscopic evaluation of the mastectomy specimen by the pathologist was used for definitive diagnosis of hematoma. The majority of these hematomas were of no clinical consequence and were usually not noted by the clinician. None of the hematomas required surgical drainage. Hematomas were determined pathologically in 64/162 patients (39.5%). Hematomas developed in 33/105 patients (31.4%) with deep wound approximation of breast parenchyma by suture compared to the higher rate seen in 31/57 patients (54.4%) without deep wound approximation (P = 0.004). This study supports the use of deep suture approximation after excisional biopsy for breast cancer.

Biopsy↗

Irrigation does not dislodge or destroy tumor cells adherent to the tumor bed.

Local recurrences in the surgical bed after tumor resection may be due to residual tumor cells "dropping" into the wound. Irrigation with water is often used to remove these cells. We designed experiments to determine whether irrigation would prevent tumor recurrence. Surgical wounds of uniform size in C57BL/6 mice were seeded with 5 x 10(2), 5 x 10(3), 5 x 10(4), 5 x 10(5), or 5 x 10(6) viable syngeneic B16-F10 melanoma cells to test the hypothesis that irrigation with water would decrease local tumor recurrence. The tumor-contaminated wounds were irrigated with distilled water or with saline (0.9% NaCl) immediately or 5, 30, 60, 120, or 240 min after seeding. Control wounds were seeded but not irrigated. The technique of irrigation was altered in a second group of experiments such that the amount of time the tumor cells were exposed to the water or saline was 5, 10, or 15 min. To determine the rapidity and durability of tumor cell attachment to host tissue, 1 x 10(4) viable B16-F10 tumor cells were seeded in vitro onto freshly cut disks of syngeneic mouse dermis. The tissue was irrigated with saline or distilled water 0, 2, 5, 10, 15, 30, 60, 120, or 240 min later. Tumor growth was observed in all the mice and neither the mechanical action of irrigation nor the hypotonic effect of distilled water changed the rate of growth. Scanning electron microscopy (SEM) demonstrated stable and firm attachment to mouse tissue within seconds of seeding with no noticeable dislodgement or cytotoxicity by either saline or water irrigation. The data suggest that the commonly used technique of irrigating the bed of the resected tumor may not be of value in preventing local recurrences.

Animals↗

A spontaneous subcutaneous tumor in C57BL/6 mice that metastasizes to the liver.

A malignant tumor that arose spontaneously in the subcutaneous tissue of the back of a C57BL/6 female mouse was found to metastasize spontaneously to the liver. The primary and metastatic tumors, SML (spontaneous metastasis to the liver) 1 and SML 2, were established in vitro in long-term cell suspension culture and were passaged 10 times in vivo for 18 months. When 100,000 cells were injected subcutaneously in the orthotopic position, tumor growth appeared in 60% of the SML 1 mice and 100% of the SML 2 mice. SML 1 did not grow when injected in the footpad, while SML 2 did. The median survival was 47 days for SML 1 and 48.5 days for SML 2 (P = 0.013). The pattern of metastasis was similar for both tumor cell lines, irrespective of intravenous or subcutaneous injection routes. Spontaneous metastasis of the SML 2 line occurred from both the orthotopic and heterotopic sites, while the SML 1 metastasized spontaneously from the orthotopic site only. Liver metastasis appeared in > 90% of the mice for both SML 1 and SML 2. Metastasis to the spleen occurred in about half the mice. Other sites of metastasis were the ovaries (36% and 52%, respectively, for SML 1 and SML 2), the kidneys (approximately 15%) and the small bowel (very rarely). Metastasis to the lungs did not occur except very rarely in the later passages of the SML 2 line. Histologic, immunohistochemical and electron microscopic studies showed a histiocytic tumor with macrophage characteristics. The cells exhibited chemotaxis toward liver extracellular matrix and reduced motility toward collagen IV, laminin and fibronectin compared to the B16-F10 melanoma line. This spontaneously occurring tumor should prove useful for the study of organ-specific metastasis to the liver.

Animals↗

Metachronous second primary malignant fibrous histiocytoma in two skeletal muscles.

The first recorded case of a metachronous second primary malignant fibrous histiocytoma (MFH) of soft tissue is presented. The patient, who has been followed every two months since the treatment of his buttock sarcoma by neoadjuvant therapy, is free of disease 24 months later. The clinical presentations, different histologies, and DNA contents of these two MFHs are consistent with metachronous primary sarcomas. The literature on second primary neoplasms is discussed.

Aged↗