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1.
Eur J Surg Oncol ; 43(7): 1273-1281, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28215733

ABSTRACT

OBJECTIVES: To evaluate outcomes of our breast frozen section (FS) practice in its first 5 years, including our specialized FS of margins (FSM) procedure for breast conserving therapy (BCT) patients. METHODS: One thousand two hundred and forty eight patients undergoing 1303 breast FSM and/or sentinel lymph node (SLN) FS were included. Clinicopathologic features were assessed by chart review. RESULTS: Use of SLN FS declined, from 43.5% of FS cases before to 19.2% of FS cases after 2012. FSM patients had a decline in overall reexcision to 12.3% in 2013-2014 (p = 0.063). There was also decline in reexcision for focally close margins (p < 0.0001) but no change in reexcision for extensively close margins. Reexcision was significantly associated with lobular subtype, multifocality and larger (≥T2) size. False negative FSM cases were most often influenced by extensively close or positive final (reexcised) margins sent for permanent section only (96/148; 64.9%). CONCLUSIONS: Despite changing surgical practices, FSM remains a valuable service that reduces reexcision in BCT patients.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Lobular/pathology , Frozen Sections/statistics & numerical data , Margins of Excision , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Breast Neoplasms, Male/pathology , Breast Neoplasms, Male/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Lobular/surgery , Female , Frozen Sections/trends , Humans , Intraoperative Period , Male , Mastectomy, Segmental/methods , Middle Aged , Reoperation , Sentinel Lymph Node/pathology , Sentinel Lymph Node Biopsy/methods , Surgicenters , Tumor Burden , Young Adult
2.
Br J Dermatol ; 162(1): 129-36, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19709103

ABSTRACT

Background Animal-type melanoma is a rare distinct melanoma subtype, characterized by proliferation of heavily pigmented epithelioid and spindled melanocytes that resembles the heavily pigmented melanomas seen in grey horses. While animal-type melanoma is generally considered to be more indolent than conventional melanoma, only a limited number of cases have been reported and, as such, the clinical characteristics of animal-type melanoma are incompletely understood. Objectives To characterize the clinical and histopathological features of animal-type melanoma, and determine any features that may predict outcome. Patients/Methods Data was extracted from a prospectively collected melanoma database (1994-2008), and a retrospective pathology database (1991-2008) for all patients with a diagnosis of both equivocal (8) and unequivocal (14) malignant animal-type melanoma. We reviewed the clinical and histopathological features, including the sentinel lymph node biopsy (SLNB) status. Results A total of 22 patients were identified, with a median age of 35 years. The median Breslow depth was 2.22 mm. A SLNB was performed in 17 patients, eight (47%) were positive. Younger age was associated with: (i) animal-type melanoma with features equivocal for malignancy (median age of 7 vs. 48 years, P = 0.01), and (ii) a negative SLNB (median age 12 vs. 53 years, P = 0.03). Four patients with unequivocal animal-type melanoma developed recurrent metastatic disease, with one patient death. No patient with an equivocal animal-type melanoma or negative SLNB developed recurrent disease; however, this did not reach statistical significance (P = 0.13 and P = 0.09, respectively). Conclusions Animal-type melanoma has a propensity for regional lymphatic metastasis and is rarely capable of disseminated metastatic disease and death. Animal-type melanoma appears to exhibit a spectrum of biological behaviour, with young patient age associated with more indolent disease.


Subject(s)
Melanoma/pathology , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Animals , Child , Child, Preschool , Female , Humans , Lymphatic Metastasis/pathology , Male , Melanoma/mortality , Middle Aged , Retrospective Studies , Skin Neoplasms/mortality , Survival Analysis , Young Adult
3.
Minerva Chir ; 61(2): 141-54, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16871145

ABSTRACT

While multimodality therapy has become the standard for most solid tumors, the mainstay of therapy for melanoma remains surgical. This includes not only early stage disease, but advanced melanoma as well. The surgical approach to melanoma has changed dramatically, with a trend towards less aggressive resection of the primary tumor, and towards a more aggressive approach to regional and metastatic disease. Melanoma surgery has been altered by our knowledge of the biology of the disease, and the results of well-designed, prospective randomized trials. Conversely, new surgical approaches have expanded our understanding of melanoma biology, and new randomized trials are needed to further define the optimal surgical approach. This article will review the evolution of melanoma surgery and the evidence behind today's recommendations.


Subject(s)
Melanoma/surgery , Skin Neoplasms/surgery , Humans , Lymph Node Excision , Lymphatic Metastasis , Melanoma/pathology , Melanoma/secondary , Neoplasm Staging , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathology
4.
Clin Exp Med ; 4(2): 65-77, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15672943

ABSTRACT

The incidence of malignant melanoma has been rising steadily for the last 30 years. Through physician and patient education, surveillance of high-risk individuals, and biopsy of any suspicious lesions, more lesions are being diagnosed earlier, where there is a high cure rate. Unfortunately many patients will still present with thicker lesions or nodal involvement, which carries a significantly worse prognosis. Over the past decade, there have been several changes in the management of primary cutaneous melanoma. These have stemmed from novel surgical approaches, a new understanding of melanoma biology, and randomized clinical trials designed to improve outcome and decrease the morbidity of therapy. This article will review the clinical evidence behind the current treatment recommendations for primary cutaneous melanoma as well as some of the emerging data on innovative immunologic-approaches to melanoma treatment.


Subject(s)
Melanoma/therapy , Skin Neoplasms/therapy , Adjuvants, Immunologic/therapeutic use , Cancer Vaccines/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/therapeutic use , Humans , Interferon alpha-2 , Interferon-alpha/therapeutic use , Lymphatic Metastasis , Melanoma/secondary , Recombinant Proteins , Skin Neoplasms/pathology
5.
Surgery ; 130(3): 470-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11562672

ABSTRACT

BACKGROUND: We previously demonstrated that the intratumoral injection of biodegradable polylactic acid microspheres that were loaded with interleukin (IL)-12 can induce a systemic antitumor immunity. We sought to investigate the clinical potential as neoadjuvant therapy. METHODS: Mice were inoculated with 5 x 10(7) Line-1 cells subcutaneously. Six days later, a single intratumoral injection of IL-12- or BSA-loaded microspheres were given; 14 days later, autopsy was performed to document metastases. Mice were inoculated with 5 x 10(7) Line-1 cells and 10 days later either treated with IL-12- or BSA-loaded microspheres or resected. Treated tumors were resected 6 days after treatment. Mice were observed 45 days for local recurrence before autopsy. RESULTS: Intratumoral injection of IL-12 microspheres resulted in significant suppression of tumor growth compared with controls (599 +/- 255 mm(3) vs 1591 +/- 372 mm(3); P =.001) and pulmonary metastases (0.4 vs 3.8 nodules per mouse; P =.003). Given before the operation, IL-12-loaded microspheres both decreased the local recurrence rate (100% to 40%) and pulmonary metastases (5.2 vs 0.6 nodules per mouse; P =.06). Earlier resection did not improve local recurrence or distant metastases. CONCLUSIONS: Intratumoral injection of IL-12-loaded polylactic acid microspheres promotes the development of systemic antitumor immunity that can eradicate micrometastases. As a neoadjuvant therapy, this can result in decreased local and distant recurrence.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/prevention & control , Adjuvants, Immunologic/administration & dosage , Interleukin-12/administration & dosage , Neoadjuvant Therapy , Skin Neoplasms/drug therapy , Adenocarcinoma/immunology , Adenocarcinoma/secondary , Adjuvants, Immunologic/therapeutic use , Animals , Immunity/drug effects , Injections, Intralesional , Interleukin-12/therapeutic use , Lactic Acid , Mice , Mice, Inbred BALB C , Microspheres , Neoplasm Recurrence, Local/prevention & control , Polyesters , Polymers , Skin Neoplasms/immunology , Tumor Cells, Cultured
6.
Am J Clin Oncol ; 24(4): 425-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11474280

ABSTRACT

Doxorubicin-based chemotherapy in the adjuvant treatment of breast cancer has become standard. Use of doxorubicin is limited by cardiac dysfunction; however, the incidence is dramatically reduced by limiting the dose to less than 550 mg/m(2). Although the cumulative dose in breast cancer is typically 240 mg/m(2), multiple gated acquisition (MUGA) scans are still recommended for determining cardiac functional status in these patients. To examine the need for this practice, we reviewed 296 patients who underwent surgery for breast cancer at Roswell Park Cancer Institute between July 1997 and December 1998. Fifty-nine of 95 (62%) patients receiving doxorubicin-based regimens, and 3 of 39 (7%) receiving nondoxorubicin regimens had pretreatment MUGA scans. The MUGA scans showed normal results in 58 patients and low-normal in 4 (6.5%), with no wall motion abnormalities encountered. There were no cases where doxorubicin was not used because of an abnormal MUGA scan. There were no cardiac complications in the 59 women who received doxorubicin-based chemotherapy. MUGA will screen out few, if any, women under consideration for doxorubicin-based adjuvant therapy; the decision to avoid doxorubicin can be made based on age and preexisting comorbidity. Guidelines recommending routine use of MUGA before the administration of doxorubicin for adjuvant therapy for breast cancer should be reconsidered.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/therapy , Doxorubicin/adverse effects , Gated Blood-Pool Imaging , Heart Diseases/chemically induced , Heart Diseases/diagnostic imaging , Adult , Aged , Chemotherapy, Adjuvant , Doxorubicin/administration & dosage , Female , Humans , Middle Aged , Risk Factors
7.
J Surg Oncol ; 77(4): 243-6, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11473372

ABSTRACT

BACKGROUND AND OBJECTIVES: While sentinel lymph node biopsy is considered by many to have replaced axillary node dissection in the management of breast cancer, concerns remain regarding false-negative results. METHODS: To investigate the accuracy of sentinel node biopsy, we reexamined all sentinel and nonsentinel nodes with multilevel sectioning and immunohistochemical staining in 42 consecutive cases of breast cancer in which sentinel node biopsy was performed and followed by axillary dissection. RESULTS: By routine hematoxylin and eosin (H&E) staining, 34% of patients were found to be node positive, with no cases of false-negative sentinel node biopsy. Reevaluation of 775 negative sentinel and nonsentinel nodes with an additional two levels and immunohistochemistry identified three "node-negative" patients who had micrometastases in the sentinel node, increasing detection in 8% of cases. More important, is the fact however, that there were no cases where additional sections and immunohistochemistry identified metastases in nonsentinel nodes that had bypassed the sentinel node. The accuracy of the sentinel node in predicting the nodal status was 100%. CONCLUSIONS: Cytokeratin immunohistochemistry will identify more patients with nodal micrometastases; however, it was unable to identify any cases where micrometastases were present in nonsentinel nodes when the sentinel node was negative. The status of the sentinel node accurately identifies the status of the axillary basin.


Subject(s)
Breast Neoplasms/pathology , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy/standards , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Keratins/analysis , Lymph Node Excision , Middle Aged
8.
Breast Dis ; 12: 131-40, 2001.
Article in English | MEDLINE | ID: mdl-15687613

ABSTRACT

Recent trends in the management of early breast cancer have moved toward breast conservation, without a loss in disease-free intervals or overall survival. The in situ ablation of breast tumors without the need for lumpectomy is the next logical extension of this trend. Advances in stereotactic guided localization, ultrasound and magnetic resonance imaging (MRI) technology has markedly improved our ability to visualize, biopsy and possibly treat breast tumors. With these technologies, probes for delivery of energy for ablating tumors and for monitoring the effect can be placed precisely within breast tumors. Several methods are available to destroy tumors in situ, based on thermal destruction of tumor with either heat or cold. Cryoablation is performed using a liquid-nitrogen cooled needle. Heating techniques include delivery of the heat through probes placed in the lesion to conduct radiofrequency irradiation or laser light energy. Two techniques, focused ultrasound and focused microwave thermotherapy, are truly non-invasive in that they do not involve any skin puncture. In addition to the incentive of eliminating lumpectomy from the treatment paradigm for early stage breast cancer, and the potential cosmetic advantages, in situ ablation may also provide an immunological benefit by providing a source of antigens for the development of a systemic anti-tumor immune response. The augmentation of this response may provide an advantage to in situ ablation in terms of recurrence and survival rates.

9.
Sarcoma ; 5(3): 133-7, 2001.
Article in English | MEDLINE | ID: mdl-18521439

ABSTRACT

A report of alveolar soft part sarcoma metastatic to the small bowel is presented. Hematogenous metastases to the small bowel from primary tumors outside the abdominal cavity are uncommon, and most remain asymptomatic and are not discovered until autopsy. However, small bowel metastases can lead to intestinal obstruction, intussuseption or even perforation. While metastases to the small bowel have been described for other tumor types, including melanoma and lung cancer, this is extremely uncommon for sarcoma, especially alveolar soft part sarcoma. We describe a 42-year-old male with a long history of alveolar soft part sarcoma, metastatic to the lung and brain, who developed an intussuseption from metastases to the small bowel.

10.
Surgery ; 128(4): 556-63, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11015088

ABSTRACT

BACKGROUND: Sentinel lymph node biopsy (SLNB) has rapidly evolved into the standard of care for clinically node-negative melanoma. Since adopting sentinel lymph node (SLN) technology in 1993, we have periodically reviewed our institution's results and made several modifications. METHODS: From January 1993 to December 1998, 182 patients with clinically node-negative primary cutaneous melanoma underwent SLNB. Charts were retrospectively reviewed and assessed for the technique for the identification of the SLN, the pathologic analysis, and the use of intraoperative frozen section. RESULTS: The accuracy of SLN identification improved from 91% to 100% with the combination of isosulfan blue dye and radiolabeled colloid over isosulfan blue dye alone. Routine versus selective lymphoscintigraphy identified 7 in-transit SLNs and increased detection of dual nodal basin drainage (15%-27%). Identification of micrometastases in the SLN increased from 14% to 24% after a modification of pathologic evaluation. The positive SLN was the only involved node in most patients (80%). Intraoperative frozen section had a sensitivity of 58% and was of benefit in only 13 of 124 patients (10%). CONCLUSIONS: Several modifications to the identification of the SLNs and the detection of metastatic melanoma have improved our outcome with SLNB. A careful, periodic review of results to identify areas for improvement at each institution is crucial to the success of SLNB for melanoma.


Subject(s)
Melanoma/secondary , Sentinel Lymph Node Biopsy/methods , Skin Neoplasms/pathology , Adult , Aged , Cancer Care Facilities , Female , Frozen Sections , Humans , Intraoperative Period , Lymphatic Metastasis , Male , Melanoma/epidemiology , Melanoma/surgery , Middle Aged , New York , Pepsinogen C , Risk Factors , Rosaniline Dyes , Sensitivity and Specificity , Sentinel Lymph Node Biopsy/standards , Skin Neoplasms/epidemiology , Skin Neoplasms/surgery
11.
Cancer Res ; 60(14): 3832-7, 2000 Jul 15.
Article in English | MEDLINE | ID: mdl-10919657

ABSTRACT

An alternative technology for the local and sustained delivery of cytokines to tumors for cancer immunotherapy was evaluated and shown here to induce tumor regression, suppression of metastasis, and development of systemic antitumor immunity. Treatment of tumor-bearing BALB/c mice with a single intratumoral injection of biodegradable polylactic acid microspheres loaded with recombinant interleukin-12 (IL-12) promoted complete regression of the primary tumor and prevented the metastatic spread to the lung. Mice that experienced tumor regression after being treated rejected a subsequent challenge with live tumor cells, which indicated the development of systemic antitumor immunity. In situ tumor vaccination, ie., injection of IL-12 microspheres into existing tumors, was superior to vaccination of mice with mixtures of tumor cells (live or irradiated) and IL-12 microspheres in inducing systemic antitumor immunity. The sustained release of IL-12 from the microspheres was superior to bolus injection of free IL-12, and intratumoral delivery of microspheres was more effective than other routes of administration. These studies establish the utility of biodegradable polymer microspheres as a clinically feasible alternative to systemic cytokine therapy and cytokine gene-modified cell vaccines for the treatment of neoplastic disease.


Subject(s)
Cancer Vaccines , Interleukin-12/administration & dosage , Microspheres , Neoplasms, Experimental/therapy , Absorbable Implants , Animals , Female , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Humans , Interleukin-12/genetics , Interleukin-2/genetics , Killer Cells, Natural/metabolism , Male , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Neoplasms, Experimental/immunology , Phospholipases A/metabolism , Polyethylene Glycols/metabolism , Recombinant Proteins/administration & dosage , Time Factors , Tumor Cells, Cultured
12.
Arch Surg ; 135(7): 831-5; discussion 836, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10896378

ABSTRACT

HYPOTHESIS: Previous studies have demonstrated an improved prognosis in patients with Barrett adenocarcinoma as compared with esophageal adenocarcinoma without Barrett. It has been suggested that an earlier presentation due to gastroesophageal reflux disease (GERD) may lead to detection of adenocarcinoma at an earlier stage. DESIGN: The records of 178 patients with esophageal adenocarcinoma presenting to Roswell Park Cancer Institute (Buffalo, NY) between 1991 and 1996 were reviewed. MAIN OUTCOME MEASURES: The clinical presentation, work-up, therapy, and outcome were compared between patients with Barrett esophagus (n = 66) and those without endoscopic or pathologic evidence of Barrett esophagus (n = 112). RESULTS: There were several favorable prognostic signs in the Barrett group, including smaller tumors, lower grade, and earlier stage. More patients in the Barrett group had surgically resectable tumors, resulting in an improved overall survival. However, there were no differences in the type or duration of symptoms. Overall, very few patients presented because of GERD, and only slightly more in the Barrett group (14% vs 4%). While survival greatly improved in patients diagnosed with Barrett due to GERD, this did not account for the difference in prognosis. CONCLUSIONS: Improved prognosis and survival for the Barrett group is not due to earlier presentation due to symptoms of GERD. It is more likely that all esophageal adenocarcinoma arises from Barrett esophagus, and that it is obscured by larger tumors. Reviews limited to resected patients greatly overestimate the number of adenocarcinoma cases diagnosed due to GERD. Increased efforts to identify high-risk patients and initiate screening are necessary to diagnose adenocarcinoma at an earlier stage.


Subject(s)
Adenocarcinoma/diagnosis , Barrett Esophagus/diagnosis , Esophageal Neoplasms/diagnosis , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Barrett Esophagus/mortality , Barrett Esophagus/pathology , Barrett Esophagus/surgery , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Female , Gastroesophageal Reflux/diagnosis , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Risk Factors , Treatment Outcome
13.
J Immunother ; 23(3): 362-8, 2000.
Article in English | MEDLINE | ID: mdl-10838665

ABSTRACT

A monoclonal antibody specific for the human analog of the murine T-cell activation molecule 4-1BB was generated and is shown here to react selectively with activated human CD4+ and CD8+ T lymphocytes. Treatment of these T cells in a one-way mixed lymphocyte culture with the anti-h4-1BB antibody enhanced the cell proliferation of the allostimulated lymphocytes. Previous studies in the mouse have shown that treatment of tumor-bearing mice with antibodies to 4-1BB augments anti-tumor immunity that is mediated by both CD4+ and CD8+ T cells. The authors consider the possibility that a similar approach may be efficacious for human cancer immunotherapy. This question was addressed by evaluating the effect of an anti-h4-1BB monoclonal antibody on human lymphocyte-mediated suppression of a human tumor xenograft in SCID mice. Mice treated with a control antibody and co-injected with the tumor and peripheral blood lymphocytes exhibited a lymphocyte dose-dependent suppression of tumor growth. In mice treated with the anti-h4-1BB antibody, the lymphocyte-mediated tumor suppression was completely eliminated and tumors grew progressively (as was observed in mice inoculated with tumors without lymphocytes). This monoclonal antibody specific for anti-h4-1BB, which augments the proliferation of allostimulated cells in vitro, blocks T-cell anti-tumor activity in vivo. These results suggest that although 4-1BB plays a role in the human peripheral blood lymphocyte-mediated suppression of tumor growth, antibodies to this molecule on human cells fail to stimulate anti-tumor activity, as was observed in tumor-bearing mice treated with an antibody to murine 4-1BB.


Subject(s)
Lung Neoplasms/immunology , Lymphocytes/immunology , Receptors, Nerve Growth Factor/immunology , Receptors, Tumor Necrosis Factor/immunology , Severe Combined Immunodeficiency/immunology , Animals , Antibodies, Monoclonal/pharmacology , Antigens, CD , CD4 Antigens/immunology , CD8 Antigens/immunology , Dendritic Cells/immunology , Humans , Isoantigens/immunology , Lymphocyte Activation , Lymphocyte Culture Test, Mixed , Mice , Neoplasm Transplantation , Transplantation, Heterologous , Tumor Cells, Cultured , Tumor Necrosis Factor Receptor Superfamily, Member 9
14.
Cancer Immunol Immunother ; 49(2): 101-8, 2000 May.
Article in English | MEDLINE | ID: mdl-10823420

ABSTRACT

PURPOSE: The poor prognosis associated with lung cancer is related to the high incidence of regional and distant metastasis. There is a crucial need to identify parameters that can predict a tendancy to metastatic spread to allow better prognostic evaluation and therapeutic approach. METHODS: Using flow cytometry we evaluated 18 human lung cancer cell lines for the expression of different surface markers on lung cancers suggested to be possible prognostic parameters, including epidermal growth factor receptor (EGFR), intercellular adhesion molecule 1 (ICAM-1), Fas and CD40. RESULTS: No correlation was found between tumor prognosis and EGFR, ICAM-1 or Fas. However, a statistically significant correlation was found between the surface expression of CD40 and the metastatic spread of the tumor. In this study, 14 of 18 lung cancer cell lines (78%) expressed CD40 on their surface. All of the 4 tumors that were CD40-negative, were stage I tumors, without any evidence of regional or distant metastasis. Of the 14 tumors that expressed CD40, all but 1 (93%) had either nodal or systemic metastasis at the time of diagnosis. Patients whose tumors were CD40-negative showed a significantly better N stage, overall stage at presentation and survival than those patients with CD40-positive patients. No significant differences between the two groups were observed in tumor size, gender, age, histology, differentiation or preoperative therapy. CONCLUSIONS: These results suggest that CD40 expression on lung cancer may play a role in metastatic spread, and also may serve as a prognostic marker and an indicator of advanced disease.


Subject(s)
CD40 Antigens/analysis , Lung Neoplasms/chemistry , Neoplasm Metastasis , ErbB Receptors/analysis , Humans , Intercellular Adhesion Molecule-1/analysis , Lung Neoplasms/pathology , Prognosis , Tumor Cells, Cultured
15.
J Immunol Methods ; 233(1-2): 57-65, 2000 Jan 13.
Article in English | MEDLINE | ID: mdl-10648856

ABSTRACT

The accurate measurement of the response of a tumor to a given treatment is critical to evaluating novel therapeutic modalities. An experimental design is reported here that can be generally applied to monitoring human tumor xenografts growing in immunodeficient mice. A human non-small cell lung tumor cell line was transfected with a mammalian expression vector containing the gene encoding human prostate specific antigen (PSA) and has been shown to grow progressively following the subcutaneous, intraperitoneal and intravenous inoculation of the tumor into severe combined immunodeficient (SCID) mice. The transfected human tumor cells produce PSA that accumulates in the sera of all tumor inoculated SCID mice. An enzyme-linked immunoassay using a rabbit polyclonal and a mouse monoclonal antibody specific for PSA was designed and tested for the detection and quantification of serum PSA in tumor-bearing mice. Over a 5-week period, the serum levels of PSA of mice inoculated subcutaneously with the tumor increased progressively, and the estimated tumor volumes correlated with the amount of PSA detected in the serum. Serum PSA levels correlated even better with total tumor mass following the intraperitoneal inoculation of tumor cells into SCID mice. Serum PSA levels fell rapidly following the surgical debulking of tumor xenograft, reaching background levels of PSA in the serum 1 week after tumor removal. Serum PSA levels were also observed in SCID mice inoculated intravenously with a PSA transfected human lung tumor cell line adapted to grow orthotopically in the lung. The transfection of human tumors with a tumor marker and the use of an immunoassay to detect this marker establish an experimental design that provides a reliable, non-invasive, accurate and simple approach to monitor and quantify the growth of human tumor xenografts in SCID mice.


Subject(s)
Biomarkers, Tumor/blood , Enzyme-Linked Immunosorbent Assay/methods , Neoplasms, Experimental/blood , Animals , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/surgery , Genetic Vectors , Humans , Lung Neoplasms/blood , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Male , Mice , Mice, SCID , Neoplasm Transplantation , Neoplasms, Experimental/genetics , Neoplasms, Experimental/surgery , Prostate-Specific Antigen/blood , Prostate-Specific Antigen/genetics , Rabbits , Transfection , Transplantation, Heterologous , Tumor Cells, Cultured
16.
Am Surg ; 64(8): 738-41; discussion 741-2, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9697903

ABSTRACT

Fine-needle aspiration biopsy (FNAB) of thyroid nodules has resulted in fewer patients needing thyroidectomy. Nondiagnostic FNAB specimens may require surgery for diagnosis. Ultrasound can help decrease nondiagnostic biopsies by visualizing lesions and guiding biopsy needles. Between 1996 and 1997, 76 patients had ultrasound-guided needle biopsies of thyroid nodules. Sixteen patients had clearly palpable nodules, whereas 19 were described as difficult to palpate. There were 32 patients who presented with either prominent thyroids or enlarged lobes. Six patients presented only with nonspecific symptoms, and 3 had nodules discovered incidentally on imaging studies. Biopsies were diagnostic in 73 of 76 (96%) patients. This varied with the size of the nodule, with the rate of nondiagnostic biopsies being 13 per cent in lesions <1.0 cm and 3 per cent in lesions >2.0 cm. Fifteen patients had surgery based on the FNAB, with a surgical yield of malignancy of 47 per cent. Ultrasound-guided FNAB is extremely useful in evaluating thyroid lesions that are difficult to palpate or nonpalpable, as well as the remainder of the gland and surrounding structures. The use of ultrasound guidance in performing FNAB results in a low rate of nondiagnostic biopsies, which may decrease the number of unnecessary thyroidectomies performed to rule out malignancy.


Subject(s)
Biopsy, Needle , Thyroid Nodule/diagnosis , Ultrasonography, Interventional , Biopsy, Needle/methods , Humans , Retrospective Studies , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgery , Thyroid Nodule/surgery
17.
Am Surg ; 63(7): 660-3; discussion 663-4, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9202544

ABSTRACT

Solitary, palpable thyroid nodules are common, but only a small percentage are malignant. It is important to evaluate these nodules in a cost-efficient manner that avoids missing a cancer. Historically, radioisotope imaging has played a major role in the workup of thyroid nodules; however, with the advent of fine needle aspiration biopsy (FNAB), this role has become less clear. From 1974 to 1994, 770 patients with a solitary nodule underwent thyroidectomy. Preoperatively, 471 had thyroid scans, and 149 had FNAB. The incidence of carcinoma in nodules excised on the basis of thyroid scan was 23 per cent, whereas the incidence of carcinoma was 37 per cent when FNAB was used (P = 0.003). Fine needle aspiration was a significantly better predictor of malignancy than thyroid scan and resulted in a smaller proportion of excisions for benign nodules. Thyroid scan provided little additional information in those patients who underwent FNAB. Because thyroid scans add little in determining which nodules require surgical excision, they should no longer be a routine part of the evaluation of a solitary thyroid nodule.


Subject(s)
Thyroid Gland/diagnostic imaging , Thyroid Nodule/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy, Needle , Child , Evaluation Studies as Topic , Female , Humans , Male , Middle Aged , Radionuclide Imaging , Retrospective Studies , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/surgery , Thyroid Nodule/pathology , Thyroid Nodule/surgery , Thyroidectomy
18.
Arch Surg ; 132(1): 28-33; discussion 34, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9006549

ABSTRACT

OBJECTIVE: To determine the feasibility and efficacy of cryosurgery of breast cancer. DESIGN: In phase 1, carcinogen-induced mammary adenocarcinomas in 13 Sprague-Dawley rats were treated by cryosurgery and were then examined for histopathologic change. In phase 2, transplantable mammary adenocarcinomas in 50 DBA/IJ mice were treated by cryosurgery to determine the effect of varying tumor temperatures, and duration and number of freeze-thaw cycles on tumor viability. In phase 3, 2- to 3-cm ultrasound-monitored cryolesions were formed in the breasts of 4 dogs and 4 sheep. These animals were followed up for procedure-related complications; the histopathologic necrosis of the cryolesions were correlated with the ultrasound images. Based on the results of these experiments, ultrasound-guided cryosurgery of breast cancer was initiated in a human clinical trial. RESULTS: In phase 1, a single, short-term (< 7 minutes) freeze killed only tumors smaller than 1.5 cm in diameter, despite an apparent decrease to -40 degrees C at the periphery of each tumor. In phase 2, varying the peripheral tumor temperature to as low as -70 degrees C, using a single, short-term (< 7 minutes) freeze did not alter the results from phase 1. If the ice ball fully encompassed the tumor, however, maintaining it for at least 15 minutes achieved 100% tumor kill independent of tumor size. In phase 3, creation of a reproducible ultrasound-monitored cryolesion was facilitated when 2 freeze-thaw cycles were performed. No procedure-related complications were noted. In the human trial, 2 invasive lobular carcinomas from 1 patient were treated by cryosurgery and were negative for persistent tumor by core needle biopsy performed 4 and 12 weeks after a well-tolerated procedure. CONCLUSIONS: In situ breast cryosurgery has been proved to be feasible and efficacious in small and large animal studies and has been successfully performed in 1 patient with breast cancer. The results of this study suggest that ultrasound-guided cryosurgery of breast cancer warrants further investigation.


Subject(s)
Adenocarcinoma/surgery , Breast Neoplasms/surgery , Cryosurgery , Mammary Neoplasms, Animal/surgery , Adenocarcinoma/diagnostic imaging , Aged , Animals , Breast Neoplasms/diagnostic imaging , Cryosurgery/methods , Dogs , Feasibility Studies , Female , Humans , Mammary Neoplasms, Animal/diagnostic imaging , Mice , Mice, Inbred DBA , Rats , Rats, Sprague-Dawley , Sheep , Ultrasonography
19.
Surgery ; 122(6): 1021-6; discussion 1026-7, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9426415

ABSTRACT

BACKGROUND: This study evaluates the indication for frozen section (FSx) in the management of the solitary thyroid nodule given the increasing use of fine-needle aspiration biopsy (FNAB). METHODS: The charts of 561 patients who underwent thyroidectomy for a solitary nodule were reviewed. Each patient underwent either FNAB, FSx, or both. Results were compared to the final diagnosis to evaluate their effectiveness in predicting malignancy. RESULTS: The sensitivity and specificity for FNAB alone (162 patients) were 86% and 91%, respectively, and for FSx (494 patients) 79% and 99%, respectively. The routine use of FSx with diagnostic FNABs did not improve the accuracy over either test alone. Sensitivity, specificity, and accuracy were essentially unchanged when the use of FSx was limited to just atypical FNAB but dropped significantly when FSx was not used. CONCLUSIONS: When results of FNAB and FSx are interpreted as benign or malignant, both are highly accurate predictors of malignancy. Routine use of FSx and FNAB does not improve the sensitivity or specificity in the detection of malignancy over that of either examination alone. FSx proved useful in determining the extent of operation only when results of the FNAB were atypical.


Subject(s)
Thyroid Nodule/pathology , Biopsy, Needle , Frozen Sections , Humans , Sensitivity and Specificity , Thyroid Nodule/surgery
20.
Surg Oncol ; 6(3): 171-7, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9576632

ABSTRACT

At Roswell Park Cancer Institute, we have seen a dramatic increase in the need for long-term venous access. Chronic venous catheters are an indispensible part of the treatment provided to oncology patients. Cancer patients are often at higher risk for complications secondary to their underlying disease and treatments. These risks may be minimized by paying close attention to several important aspects of central line placement. These include matching individual patient needs with the access device most suited to those needs, a thorough preoperative assessment, and the safest and most appropriate operative approach for placement. Likewise, the prompt recognition and treatment of complications when they do occur is crucial to the care of these patients. In order to optimize the care of patients with long-term venous access devices, we have reviewed our experience of over 700 vascular access consultations and offer the following recommendations.


Subject(s)
Bacterial Infections/prevention & control , Catheterization, Central Venous/methods , Infection Control/methods , Neoplasms/therapy , Bacterial Infections/etiology , Cancer Care Facilities , Catheterization, Central Venous/adverse effects , Catheters, Indwelling/adverse effects , Female , Humans , Male , New York
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