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Biomedical subjects

M J Mastrangelo

Publications and source records attributed to M J Mastrangelo.

At least 19 recordsLinked to original sources
PubMed2001

Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases.

A human cancer vaccine composed of autologous tumor cells modified with the hapten dinitrofluorobenzene (DNP) induces cell-mediated immunity to the tumor cells and the development of inflammatory responses within metastatic sites. In this study we determined whether DNP vaccine could induce regression of established metastases. Ninety-seven patients (83 evaluable) with surgically incurable metastatic melanoma were treated with DNP vaccine preceded by low-dose cyclophosphamide. Tumor regression was assessed by standard criteria. The development of cell-mediated immunity to melanoma-associated antigens was measured by delayed-type hypersensitivity (DTH) testing before and after DNP vaccine treatment. Survival analysis was performed by the Kaplan-Meier method. There were 11 antitumor responses: 2 complete, 4 partial and 5 mixed. Both complete responses and 2 of the 4 partial responses occurred in patients with lung metastases. Response durations were as follows: partial responses-5, 6, 8 and 47+ months; and complete responses-12 and 29 months. Tumor regression required at least 4 months to become evident and in 2 cases maximum regression was not observed until 1 year after beginning treatment. Patients who exhibited tumor regression survived longer than those who did not (median survival times: responders, 21.4 months; non-responders, 8.7 months; p = 0.010). DTH to DNP-modified and unmodified autologous melanoma cells was induced in 87% and 42% of patients, respectively. The DTH response to unmodified cells was significantly associated with prolonged survival. Autologous DNP-modified melanoma vaccine can induce clinically meaningful regression of metastases and small lung metastases appear to be unusually sensitive. The development of DTH to unmodified, autologous tumor cells may be an important indicator of the vaccine's efficacy.

Adult↗
PubMed2001

Obesity and laparoscopic repair of ventral hernias.

BACKGROUND: Laparoscopic ventral hernia repair (LVHR) is gaining acceptance and compares favorably with open repair. Patients who are morbidly obese (MO) traditionally have been considered poor surgical candidates for ventral hernia repair because of their associated comorbidities and risk of postoperative wound infection and hernia recurrence. In this study we evaluated our experience with LVHR in patients who are obese and those who are morbidly obese. METHODS: All 64 patients undergoing LVHR at the University of Kentucky between September 1997 and October 2000, representing 66 hernias, were entered prospectively into a database. Data before, during, and after surgery were collected as well as follow-up data. Patients were divided into three groups on the basis of body mass index (BMI): normal to overweight (BMI < or = 29); obese (BMI 30-39), and MO (BMI > or = 40). RESULTS: There were 16 patients in the MO group, most of them women. The mean BMI was 43.9 (range, 40-60), and the mean age was 45.6 years (range, 25-68 years). The location of defects was similar among the groups, as were the number of prior repairs. The operative time and length of stay for the MO group tended to be longer than for the other two groups. Five minor complications occurred in the MO group. During a follow-up period ranging from 1 to 35 months, there were no recurrences. CONCLUSION: Laparoscopic repair of ventral hernias in patients who are morbidly obese is both safe and feasible, and can be performed with minimal morbidity. At this writing, there have been no recurrences, but long-term follow-up evaluation is required.

Adult↗
PubMed2001

Using immersive VR as a tool for preoperative planning for minimally invasive donor nephrectomy.

For surgeons approaching minimally invasive donor nephrectomy it is important to identify variant anatomy preoperatively since this anatomy can vary significantly from patient to patient. The goal of this operation is to preserve the architecture and function of the organ so it can be transplanted and function successfully. The ability of the surgeon to navigate through an individual patient's anatomy in a virtual three-dimensional (3D) immersive environment augments understanding of anatomical relationships particular to that individual patient and facilitates conveying that information to other physicians and students. Utilizing automated 3D reconstruction of high contrast computed tomography (CT) scan files viewed in this way, surgeons reported a better preoperative understanding of the anatomical variations and encountered fewer surprises at the time of surgery.

Humans↗
PubMed2001

Immersive virtual reality used as a platform for perioperative training for surgical residents.

Perioperative preparations such as operating room setup, patient and equipment positioning, and operating port placement are essential to operative success in minimally invasive surgery. We developed an immersive virtual reality-based training system (REMIS) to provide residents (and other health professionals) with training and evaluation in these perioperative skills. Our program uses the qualities of immersive VR that are available today for inclusion in an ongoing training curriculum for surgical residents. The current application consists of a primary platform for patient positioning for a laparoscopic cholecystectomy. Having completed this module we can create many different simulated problems for other procedures. As a part of the simulation, we have devised a computer-driven real-time data collection system to help us in evaluating trainees and providing feedback during the simulation. The REMIS program trains and evaluates surgical residents and obviates the need to use expensive operating room and surgeon time. It also allows residents to train based on their schedule and does not put patients at increased risk. The method is standardized, allows for repetition if needed, evaluates individual performance, provides the possible complications of incorrect choices, provides training in 3-D environment, and has the capability of being used for various scenarios and professions.

Cholecystectomy, Laparoscopic↗
PubMed2001

Laparoscopic dissecting instruments.

The authors provide an overview of laparoscopic dissecting instruments and discuss early development, surgical options, and special features. End effectors of different shapes and functions are described. A comparison of available energy sources for laparoscopic instruments includes discussion of thermal dissection, ultrasonic dissection, and water-jet dissection. The ergonomic risks and challenges inherent in the use of current laparoscopic instruments are outlined, as well as ergonomic issues for the design of future instruments. New directions that laparoscopic instrumentation may take are considered in connection with developing technology in robotics, haptic feedback, and MicroElectroMechanical Systems.

Dissection↗
PubMed2001

Phase i study of intravesical vaccinia virus as a vector for gene therapy of bladder cancer.

PURPOSE: Vaccinia virus is a DNA poxvirus previously used as a vaccine to eradicate smallpox. The virus has a high efficiency of infection, replicates in the cytoplasm without chromosomal integration and can transport a large amount of recombinant DNA without losing infectivity. Therefore, it is an excellent choice as a vector for gene delivery in vivo. Large quantities of vaccinia have been injected into dermal, subcutaneous and peripheral lymph node melanoma metastases without significant side effects, and with efficient infection of the tumor cells and recombinant gene transfection. To determine if vaccinia, when given intravesically, can effectively infect bladder mucosa and tumor with acceptable toxicity, we performed a phase I trial of intravesical vaccinia in patients with muscle invasive transitional cell carcinoma before radical cystectomy. MATERIALS AND METHODS: After documenting immune competence and demonstration of a major reaction after revaccination, patients received 3 increasing doses of intravesical Dryvax vaccinia virus (Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) that was provided by the Centers for Disease Control. Approximately 24 hours after the third dose, cystectomy was performed and the tissue was examined microscopically. RESULTS: There were 4 patients who were treated. The 3 patients who received the highest doses (100 x 106 plaque forming units) had significant mucosal and submucosal inflammatory infiltration by lymphocytes, eosinophils, and plasma cells into tumor and normal tissue. Dendritic cells were recruited to the site after exposure to the vaccinia. Significant mucosal edema and vascular ectasia were seen. Tumor and normal urothelial cells showed evidence of viral infection, including enlarged vacuolated cells with cytoplasmic inclusions. There were no clinical or laboratory manifestations of vaccinia related toxicity except mild dysuria. Of the 4 patients 3 survived and were free of disease at 4-year followup. CONCLUSIONS: Our study demonstrates that vaccinia virus can be administered safely into the bladder with recruitment of lymphocytes and induction of a brisk local inflammatory response. To our knowledge, this is the first report of direct delivery of live virus into the human bladder. The role of wild type vaccinia as immunotherapy for bladder cancer warrants further study. Furthermore, these data support the exploration of recombinant vaccinia as a putative gene therapy vector for intravesical infection and transfection of bladder tumor cells with cytokine or other genes, an approach that our group pioneered and most recently studied in patients with superficial melanoma.

Adult↗
PubMed2000

Protracted survival after resection of metastatic uveal melanoma.

BACKGROUND: The objective of this study was to evaluate the usefulness of resection of metastatic uveal melanoma and to analyze the characteristics of patients who may benefit from surgical intervention. PATIENTS AND METHODS Twelve patients underwent surgical removal of metastasis between 1976 and 1998. Data regarding primary uveal melanoma, systemic metastasis, surgical procedures, and outcomes were reviewed retrospectively. RESULTS: There were seven patients with liver metastases, two with lung metastases, one with brain metastasis, and two patients with metastases in the liver and other organs. Median time to systemic metastasis was 8 years. Seven of 12 patients were asymptomatic when they were found to have metastasis. Ten patients underwent complete resection of metastasis. No significant surgical complications were experienced. Median recurrence free and overall survival periods after complete resection were 19 months (range, 6-78 months) and greater than 27 months (range, 11-86 months), respectively. Recurrence free and overall 5-year survival rates of those patients were 15.6% and 53.3%, respectively. Three of these patients had no further systemic recurrence. All patients whose time to systemic metastasis was within 5 years developed further systemic recurrence within 2 years after surgery. In contrast, in 8 patients whose time to systemic metastases was greater than 5 years, 4 patients either were recurrence free or developed second metastasis more than 4 years after surgery. CONCLUSIONS: Complete surgical removal of metastatic uveal melanoma provided unexpectedly long survival without significant morbidity for the selected patients. These results are encouraging and justify a trial in which patients eligible for resection are randomized between standard treatment and surgery.

Adolescent↗
PubMed2000

Paclitaxel and tamoxifen: An active regimen for patients with metastatic melanoma.

BACKGROUND: In early trials of paclitaxel administered as a 24-hour infusion, an overall response rate of 16% was reported for patients with metastatic melanoma. Paclitaxel is a natural product-based agent and is thus subject to the problem of multidrug resistance (MDR). Tamoxifen is an agent that can abrogate MDR and potentially enhance the effect of paclitaxel. A Phase II trial of the combination was undertaken with previously treated patients. METHODS: Patients with metastatic cutaneous or mucosal melanoma who were previously treated with the Dartmouth chemotherapy regimen (dacarbazine, carmustine, cisplatin, and tamoxifen) were evaluated. Paclitaxel was administered at a dose of 225 mg/m(2) intravenously over 3 hours every 3 weeks. All patients also took tamoxifen 40 mg orally daily. Treatment continued until disease progression. RESULTS: Twenty-one patients completed at least two cycles of paclitaxel and were evaluable for response. Five responses were observed, 1 complete response, and 4 partial responses, for an overall response rate of 24%. The combination was well tolerated. The most common nonhematologic side effects were myalgia and paresthesia. Hematologic toxicity was mild. No patients developed neutropenic fever. CONCLUSIONS: This is the first report of a Phase II trial evaluating paclitaxel as a 3-hour infusion in melanoma patients. The 3-hour infusion is well tolerated and results in little myelosuppression and minimal neurotoxicity. The contribution of tamoxifen is difficult to evaluate because plasma levels were not measured. It is possible that a higher response rate might be observed with larger doses of tamoxifen. Further investigation of paclitaxel in the treatment of patients with metastatic melanoma is warranted.

Administration, Oral↗
PubMed2000

Endoscopic retrograde cholangiopancreatography in the management of choledocholithiasis.

Surgeons today have a wide range of therapeutic options for the management of patients with choledocholithiasis. Endoscopists, interventional radiologists, and surgeons employ a variety of techniques to access and remove common bile duct stones (CBDS) successfully. Although earlier studies have been done to assess the relative merits of laparoscopic and endoscopic management of CBDS, few of them have employed a randomized prospective trial for the comparison. Without recognized parameters for comparison, no definitive conclusions can be drawn. Herein, we examine the role of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) as an important adjunct to laparoscopic cholecystectomy (LC) in the management of CBDS. The three main scenarios in which this modality is employed for CBDS removal are selective preoperative ERCP, intraoperative ERCP, and postoperative ERCP. We conclude that an appropriate balance must be struck to maintain a high yield of positive or therapeutic ERCP, avoid unnecessary ERCP, and not miss CBDS, while ensuring acceptably low rates of morbidity and mortality and controlling costs. As we await the publication of prospective data, we may look for direction from decision analysis in order to develop optimal management strategies and define the "best practice" results that should be expected of operators before new procedures and innovative technology are accepted on a widespread basis.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed2000

Laparoscopic splenectomy: outcomes and lessons learned from over 200 cases.

BACKGROUND: In this study of laparoscopic splenectomy (LS), we evaluate prospectively gathered perioperative patient data and review lessons learned in the evolution of this procedure. METHODS: At 2 university medical centers between November 1993 and March 2000, there were 203 patients (122 female patients and 81 male patients) who underwent LS after preoperative evaluation. RESULTS: LS was successfully completed in 197 patients (97%). The mean operative time was 145.5 minutes and the length of stay averaged 2.7 days with 143 (70.4%) staying less than 48 hours. The most common indication was idiopathic thrombocytopenic purpura (ITP). Six patients required conversion to open splenectomy (OS), with only 2 conversions in the last 163 cases. No deaths were attributed to the procedure. Complications occurred in 19 patients (9.3%). Thirty accessory spleens were identified in 25 patients (12.3%). Seventeen patients (8.4%) underwent concomitant procedures, most commonly cholecystectomy. CONCLUSIONS: LS by the lateral approach is both safe and feasible in patients of all ages.

Adolescent↗
PubMed1999

Immunologic approaches to the treatment of prostate cancer.

The presence of several organ-specific molecules that could serve as immunogens or targets of an immune attack, the nonessential nature of the prostate gland, the substantial failure rate after treatment of the primary tumor, and the lack of effective chemotherapy for metastatic disease make prostate cancer an ideal candidate for immunotherapy. This report reviews the current status of two novel approaches to the treatment of prostate cancer. The first is an effort to induce antitumor immunity by enriching the cytokine environment within the primary cancer by intraprostatic injection of Leukocyte Interleukin (Cel-Sci Corp, Vienna, VA), a mixture of natural cytokines that includes interleukin-1 beta (IL-1beta), IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha). The second approach uses OncoVax-P (Jenner Biotherapies, Inc, San Ramon, CA), a vaccine consisting of liposome-encapsulated recombinant prostate-specific antigen (PSA) and lipid A. When administered as an emulsion or in association with bacillus Calmette-Guérin (BCG)/cyclophosphamide or GM-CSF with or without IL-2/cyclophosphamide, immunologic tolerance is broken as evidenced by the generation of humoral and cellular immunity. Both of these approaches have been shown to be feasible and safe, and are now being tested in patients with less advanced disease to determine if manipulation of the immune system can favorably influence clinical outcome.

Cancer Vaccines↗
PubMed1998

Systemic therapy in melanoma.

The patient with surgically incurable melanoma presents a difficult problem for the medical oncologist. Single chemotherapeutic agents at conventional doses produce bona fide but infrequent remissions. The most active single agent for the treatment of metastatic melanoma is dacarbazine (DTIC). Until recently, combinations of drugs yielded no real improvement over treatment with the individual components. The combination of DTIC + carmustine (BCNU) + cisplatin + tamoxifen (the "Dartmouth regimen") appears to be more effective than DTIC alone, but prospective randomized trials comparing the two are still in progress. The contribution of tamoxifen to the observed results continues to be evaluated. Biological agents, such as interferon and interleukin-2, have lower overall response rates compared to chemotherapy regimens, but response duration appears to be longer. Chemotherapy combined with biotherapy offers the promise of higher response rates and long-term durable remissions. The results from high-dose regimens that use autologous bone marrow or peripheral stem cell support have not been sufficient to justify the added toxicity. Although advanced melanoma often is not curable with systemic therapy, the considered use of currently available regimens can induce clinically significant remissions and, possibly, prolong life in some patients.

Antineoplastic Agents↗
PubMed1998

Immunopotentiation with low-dose cyclophosphamide in the active specific immunotherapy of cancer.

This paper reviews the use of low-dose cyclophosphamide (CY) with active specific immunotherapy in patients with advanced melanoma and other metastatic cancers, and outlines the basic scientific research that supports this use. In various animal models, CY augments delayed-type hypersensitivity responses, increases antibody production, abrogates tolerance, and potentiates antitumor immunity. The mechanism of CY immunopotentiation involves inhibition of a suppressor function, as indicated by extensive work in the MOPC-315 plasmacytoma murine model. Human studies of the immunopotentiating effect of CY have yielded both positive and negative results. Toxicity associated with low-dose CY has been mild in these studies. Results of efficacy have been variable for reasons such as small sample sizes, short follow-up periods, and the weaker immunogenicity of human tumor-associated antigens. Although beneficial clinical outcomes have been observed in historically controlled trials, there are few randomized, controlled trials that evaluate outcome in relation to CY immunopotentiation of active specific immunotherapy. Additional randomized, controlled trials should be done to examine the clinical efficacy of CY immunopotentiation of therapeutic cancer vaccines.

Adjuvants, Immunologic↗
PubMed1998

Surgical removal of solitary hepatic metastasis from choroidal melanoma.

PURPOSE: To report surgical management of solitary hepatic metastasis that occurred 25 years after an enucleation for uveal melanoma. METHODS: A 16-year-old girl, diagnosed with choroidal melanoma and treated with enucleation, was found 25 years later to have liver metastasis affecting the entire left lobe of the liver. RESULTS: She underwent partial hepatectomy with removal of the metastatic melanoma. Four years later, she was found to have a smaller circumscribed nodular melanoma in the remaining right lobe of the liver, also treated with resection. She has remained disease-free for 2 years, with no evidence of systemic disease. CONCLUSION: Surgical excision may be a useful treatment option in selected cases with solitary, circumscribed liver metastasis from uveal melanoma.

Adolescent↗
PubMed1998

Phase I study of R24 in patients with metastatic melanoma including evaluation of immunologic parameters.

R24 is a mouse IgG3 monoclonal antibody with specificity for the disialoganglioside GD3. Most human melanomas have substantial surface GD3; in addition, a significant proportion of T lymphocytes display surface GD3. In a phase I study, we have investigated the toxicity and effect on selected immunological parameters of three dose levels of R24 given intravenously daily for five days (10 mg/m2/d, 30 mg/m2/d and 50 mg/m2/d) to patients with advanced melanoma. R24 administration neither consistently diminished nor augmented expression of delayed type hypersensitivity (DTH) skin reactions to anergy panel antigens or to a contact allergen dinitrofluorobenzene. R24 was infrequently found on tumor cells, or on lymphocytes from DTH biopsies, despite measurable serum levels of R24. The 30 mg/m2/d dose of R24 produced a statistically significant drop in peripheral blood lymphocytes on treatment Day 5. Likewise, on Day 5 there was a modest but statistically significant decrement in the proportion of circulating cells which were R24+. While there was one mixed response, there were no complete or partial tumor regressions in the R24 treated patients; there was no evident clinical benefit from the R24 therapy. The toxicity of the R24 at the higher dose levels can be very substantial. One patient, on the highest dose level, died on the 4th day of R24 treatment; in the absence of a plausible alternative explanation, a relationship of the death to the administered R24 must be considered. A precipitous drop in serum albumin coincident with R24 administration was found in all cases; this effect has not been previously reported with R24.

Animals↗