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M K Wallack

Publications and source records attributed to M K Wallack.

At least 37 records · Page 2Linked to original sources
PubMed1997

Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial.

OBJECTIVE: The efficacy of vaccinia melanoma oncolysate (VMO) vaccine to increase overall survival and disease-free survival of patients with surgically resected International Union Against Cancer (UICC) stage II melanoma was studied in a phase III, randomized, multi-institutional trial. SUMMARY BACKGROUND DATA: Phase I and II trials with VMO showed minimal toxicity and clinical efficacy in patients with melanoma. In a recently completed phase III VMO trial, the first interim analysis performed in April 1994 showed an increasing trend in the survival of patients treated with VMO. The second interim analysis was performed in April 1995. METHODS: Patients with surgically resected stage II (UICC) melanoma were treated with VMO (N = 104) or placebo vaccinia vaccine virus (V) (N = 113) once a week for 13 weeks and then once every 2 weeks for a total of 12 months. Patients' clinical data were collected as of May 1995 and analyzed for survival. RESULTS: In this second interim analysis, the mean follow-up time is 42.28 months. No survival difference was observed between VMO and V treatments. However, in a retrospective subset analysis, a subset of males between the ages of 44 and 57 years and having one to five positive nodes (at 2-, 3-, and 5-year intervals, 13.6%, 15.9%, and 20.3% difference insurvival in favor of VMO [N = 20] when compared to V [N = 18] [p = 0.037]) and another subset of patients with clinical stage I (at 3- and 5-year intervals, 30% and 7% difference in survival in favor of VMO [N = 20] when compared to V [N = 23], [p = 0.05]) showed significant survival advantage with VMO. CONCLUSIONS: Although VMO vaccine therapy in surgical adjuvant setting did not produce a significant survival benefit to all patients with melanoma, patients from the above two subsets had significant survival benefit.

Adult↗
PubMed1997

The role of cholecystectomy in acquired immunodeficiency syndrome.

BACKGROUND: Hepatobiliary disease is a common manifestation of acquired immunodeficiency syndrome, although the role of surgical intervention in the spectrum of therapy is unclear. STUDY DESIGN: A retrospective review was designed to evaluate the characteristics of patients given a diagnosis of human immunodeficiency virus infection or acquired immunodeficiency syndrome and undergoing cholecystectomy between January 1, 1986, and November 1, 1995. RESULTS: The study included 40 patients (35 men, 5 women; mean age, 42 +/- 9 years), 33 (82.5 percent) with acquired immunodeficiency syndrome; their mean preoperative T-helper (CD4) cell count was 163/mL3. Gross pathologic findings included acute (n = 9, 22.5 percent) and chronic (n = 31, 77.5 percent) cholecystitis. Gallbladder specimens were positive for cholelithiasis in 28 (70 percent), Cryptococcus organisms in 5 (12.5 percent), cytomegalovirus in 3 (7.5 percent), and lymphoma in 2 (5 percent). The median follow-up time was 48 months (range, 6 to 63 months). The percentage survival was 92.5 percent (n = 37) at 30 days, and 57.5 percent (n = 23), 37.5 percent (n = 15), and 25 percent (n = 10) at 12, 24, and 36 months, respectively. The mean survival time was 25.1 months. The likelihood of survival was directly linked to the CD4 cell count. The mean survival period was 25 months for patients with CD4 cell counts less than 200/mL3 compared with 48 months for those with CD4 cell counts greater than 200/mL3. CONCLUSIONS: Although the pathologic changes identified in patients with acquired immunodeficiency syndrome may occasionally be atypical, the clinical presentation, indications for operation, and pathologic findings identified are quite common. Patients tolerate cholecystectomy well with good long-term outcome and minimal infectious complications. Even in patients with the most compromised immune status, a 2-year survival after operation is acceptable. Cholecystectomy has a clear role in the spectrum of treatment for biliary disease relative to acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1997

The surgeon's database for AIDS: a collective review.

BACKGROUND: The human immunodeficiency virus infection and acquired immunodeficiency syndrome have had a dramatic effect on the practice of surgery. Critical issues include quantifying the risk encountered by surgeons when operating on infected patients, the benefits of chemoprophylaxis after injury by a health care worker, the likelihood of infected surgeons transmitting human immunodeficiency virus to patients, and the debate over mandatory testing. STUDY DESIGN: Literature review of English-language publications. RESULTS: The incidence of human immunodeficiency virus infection ranges from 1.3 percent of patients hospitalized at sentinel hospitals to 1.5/1,000 patients in lower risk environments. The rate of percutaneous injury during an operation is 5 percent to 6 percent, and human immunodeficiency virus transmission after percutaneous injury with a needle contaminated with the human immunodeficiency virus is 0.3 percent. Here, we review current Public Health Service recommendations for chemoprophylaxis after percutaneous injury and address the debate over mandatory human immunodeficiency virus testing for patients and surgeons in the context of new information regarding the test for the human immunodeficiency virus. CONCLUSIONS: Controversial issues regarding acquired immunodeficiency syndrome and the human immunodeficiency virus infection must be addressed by all surgeons on the basis of objective information.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Appendicitis in patients with acquired immunodeficiency syndrome.

BACKGROUND: Previous reports evaluating appendicitis in patients with human immunodeficiency virus/ acquired immunodeficiency syndrome have detailed unusual pathology, atypical clinical presentations, and poor outcomes. These reports have described small groups of patients and are inconsistent with larger surveys. STUDY DESIGN: A retrospective design was used to evaluate patients diagnosed with human immunodeficiency virus or acquired immunodeficiency syndrome undergoing appendectomy from 1986 to 1995. RESULTS: Fifty-five patients were evaluated (mean age 33.4 +/- 8.2 years, 98 percent male, 90 percent clinical acquired immunodeficiency syndrome, CD4 count 144.45 +/- 34 cells/mL3). Presenting symptoms included right lower quadrant pain (91 percent), nausea and vomiting (41 percent), diarrhea (22 percent), and generalized abdominal pain (24 percent). Significant findings on examination included right lower quadrant tenderness (91 percent), rebound (74 percent), fever (54 percent), abdominal distention (7 percent), and generalized abdominal tenderness (9.3 percent). Computed tomography was performed in 26 percent and findings were suggestive of appendicitis in 93 percent of cases. Operative findings included acute inflammation (83.3 percent), appendiceal rupture (24 percent), gangrene (29 percent), and normal-appearing appendices (5.5 percent). Unusual findings included Mycobacterium tuberculosis (1.8 percent), atypical mycobacterium (1.8 percent), and chronic appendicitis (3.7 percent). Thirty-day survival was 100 percent. Significant postoperative fevers were noted in 33 percent and lasted 4.63 +/- 1.2 days. The presence of prolonged postoperative fever was linked to lower CD4 counts (p = .05). Follow-up (mean time to follow-up, 1,656 +/- 970 days) was complete in 43 percent. Survival at follow-up was noted in 57.1 percent (mean length of survival after surgery, 837 +/- 155 days). CONCLUSIONS: Appendectomy in patients with human immunodeficiency virus/acquired immunodeficiency syndrome is associated with little morbidity or mortality. Atypical pathology is rarely identified. A higher than expected rate of rupture may be linked to delays before hospitalization or to impaired immune status.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Favorable clinical responses in subsets of patients from a randomized, multi-institutional melanoma vaccine trial.

BACKGROUND: A phase III, randomized, double-blind, multi-institutional trial was performed evaluating active specific immunotherapy using vaccinia melanoma oncolysate (VMO) in the surgical adjuvant setting in patients with stage II melanoma (UICC staging). The first interim analysis showed no significant difference in disease-free and overall survival. The data were further analyzed to identify subsets of patients with improved outcome when treated with VMO. METHODS: Patients received either VMO or placebo of live vaccinia vaccine virus (V), once a week for 13 weeks and then once every 2 weeks for an additional 39 weeks or until recurrence. Having stratified patients according to sex, age, number of positive nodes, tumor thickness, and clinical stage, data were analyzed for disease-free survival and overall survival. RESULTS: Male patients showed a 17% difference in overall survival at 4 years when treated with VMO (p = 0.19). A subset of male patients < 57 years of age with one to five positive nodes showed a 30% difference at 4 years with VMO (p = 0.06). Patients with clinical stage I but pathological stage II disease (both male and female), who had undergone prophylactic node dissection, showed a 23% difference in survival at 3 years with VMO (p = 0.11). CONCLUSIONS: This subset analysis shows encouraging survival benefit in certain subsets of patients and an increasing trend in overall survival. Further follow-up of this phase III trial from a second interim analysis will be forthcoming.

Adult↗
PubMed1995

A phase III randomized, double-blind multiinstitutional trial of vaccinia melanoma oncolysate-active specific immunotherapy for patients with stage II melanoma.

BACKGROUND: In a Phase II trial, surgical adjuvant active specific immunotherapy using a live vaccinia virus-augmented allogeneic polyvalent melanoma cell lysate, vaccinia melanoma oncolysate (VMO), produced a significant disease free interval (DFI) in patients with International Union Against Cancer Stage II melanoma with positive lymph nodes. Therefore, a Phase III randomized prospective, double-blind, multiinstitutional, surgical adjuvant VMO trial was performed to determine the efficacy of VMO to increase the DFI and the overall survival in this group of patients with Stage II disease. METHODS: Two hundred and fifty patients with Stage II melanoma were divided into two postsurgical groups. One group received VMO (total protein equals 2 mg/ml) and the other received the placebo of live vaccinia vaccine virus (V) (10(5.4) TCID50/ml), an adjuvant component of the VMO. Patients initially received these biologics once a week for 13 weeks and then once every 2 weeks for an additional 39 weeks or until recurrence. All surviving patients have been followed for at least 30 months. RESULTS: Statistical analysis of survival data (n = 217) for this first interim analysis shows that there is no statistically significant (P = 0.99) increase in DFI of patients treated with VMO (n = 104) when compared with V (n = 113). The median DFI is 38.0 months for patients treated with VMO and 37.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of patients treated with VMO vs. 66 and 36%, respectively, of patients treated with V were free of melanoma. The median overall survival is not available because the patients treated with VMO have not yet reached the 50% mark and the median overall survival is 45.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of VMO-treated patients survived when compared with 66 and 36%, respectively, of patients treated with V. Although the overall survival of patients treated with VMO is not statistically significant (P = 0.88) at this point, there is an increasing trend in the overall survival of patients treated with VMO; a 10% increase at the 4-year time point. Moreover, in the subset analysis, VMO-treated male patients (n = 63) showed a 17% improvement in survival at 4-year time point when compared with male patients treated with V (n = 67) (P = 0.19) at the same time point and male patients (n = 20) between the ages of 44 and 57 having 1-5 positive lymph nodes showed a 37% difference in overall survival at the 4-year time point when compared with those patients treated with V (n = 18) (P = 0.13) at the same time point. CONCLUSION: In this first interim analysis, active specific immunotherapy with VMO vs. V showed no difference in the disease free interval or overall survival. Subset analyses likewise showed no significant differences in outcome but the data suggest a potential difference in immunoreactivity between male and female patients with melanoma that awaits further follow up and may merit further investigation.

Adult↗
PubMed1995

Ligation device assisting low anterior anastomosis.

UNLABELLED: The use of the circular stapler has enabled surgeons to perform very low anterior resections where previously abdominoperineal proctectomy would be performed for carcinoma of the rectum. The use of the roticulator or other linear stapler devices has facilitated these anastomoses and precluded the necessity for pursestring sutures, thereby reducing the incidence of incomplete tissue rings, which should reduce the risk of anastomotic leaks. One significant drawback to the roticulator, especially in the narrow male pelvis, is its application for very low lesions. In many cases the stapler cannot be forced deeply enough into the pelvis to allow for a sufficient margin below the tumor. PURPOSE: The purpose of this article is to report results of a prototype that applies a gasket that automatically fixes the rectum to the rod of the circular stapler. METHOD: To date the device has been used 22 times in 14 patients (8 patients had both limbs attached using the device, whereas 6 patients had only the rectal stump attached in this manner). RESULTS: All anastomoses healed without complication, all patients had complete donuts of tissue, and only two anastomoses had to be reinforced. CONCLUSION: The use of this device may facilitate stapling of very low anastomoses for carcinoma of the rectum.

Anastomosis, Surgical↗
PubMed1995

Surgical management of melanoma.

The incidence of melanoma is rising more rapidly than any other malignancy. More conservative margins of excision have been established and the role of elective node dissection awaits determination by prospective randomized trials. Lymphoscintigraphy has clarified lymphatic drainage from watershed areas. Lymphatic mapping and sentinel node biopsy may lead to acceptance of selective lymphadenectomy, and also allows for more sensitive staging. Further advances in outcome require the development of effective systemic adjuvant therapies. Until such time, surgery continues to play a pivotal role in all stages.

Biopsy↗
PubMed1995

Coronary pseudoaneurysm after angioplasty.

Coronary pseudoaneurysm is a complication of angioplasty occurring in 4-5% of cases. The likely etiology of the pseudoaneurysm is an iatrogenic dissection. Although increasingly identified, they are infrequently reported and no large series has been documented. The case of a 64-year-old patient with a post-PTCA coronary pseudoaneurysm that was treated surgically is presented. A review of the world's literature identifies stenosis as a major cofactor in operative intervention and raises the possibility that aneurysm formation promotes stenosis.

Aneurysm, False↗
PubMed1994

Therapeutic effect of a vaccinia colon oncolysate prepared with interleukin-2-gene encoded vaccinia virus studied in a syngeneic CC-36 murine colon hepatic metastasis model.

Vaccinia CC-36 murine colon oncolysate (VCO) prepared with interleukin-2-gene encoded recombinant vaccinia virus (IL-2VCO) was used in the treatment of a syngeneic murine colon adenocarcinoma (CC-36) hepatic metastasis to test the beneficial effect of the interleukin-2-gene encoded vaccinia virus over a control recombinant vaccinia virus in producing a vaccinia oncolysate tumor cell vaccine. Results suggest that the IL-2VCO treatment significantly reduced the hepatic tumor burden in comparison with the controls that received either IL-2-gene-encoded recombinant vaccinia virus or a plain recombinant vaccinia virus or vaccinia oncolysate prepared with the plain recombinant virus. The survival of mice treated with IL-2VCO was also improved in comparison with mice treated with other preparations. The induction of a cytolytic T lymphocyte response was examined to elucidate the mechanism of the induction of antitumor responses in IL-2VCO-treated mice. Fresh peripheral blood lymphocytes (PBL) isolated from IL-2VCO-treated mice showed a higher cytolytic activity against CC-36 tumor cell target when compared to PBL from the mice of other treatment groups, suggesting that the IL-2VCO induced an antitumor cytolytic T lymphocyte response. These results suggest that a vaccinia oncolysate, prepared with recombinant vaccinia virus encoding an immunomodulating cytokine gene will enhance antitumor responses in the host.

Adenocarcinoma↗
PubMed1994

Immunotherapy of a vaccinia colon oncolysate prepared with interleukin-2 gene-encoded vaccinia virus and interferon-alpha increases the survival of mice bearing syngeneic colon adenocarcinoma.

Therapeutic effect of a vaccinia colon oncolysate prepared with interleukin-2 (IL-2) gene-encoded vaccinia virus (IL-2VCO) in combination with recombinant interferon-alpha (IFN-alpha) was studied in a syngeneic murine CC-36 colon hepatic metastasis model. Treatment with this IL-2VCO+IFN-alpha produced a higher survival rate (90% on day 60 after tumor transplantation) in mice having CC-36 hepatic metastases when compared to treatment with IFN-alpha (0%), VCO+IFN-alpha (0%), or IL-2VCO (11%). The only treatment that produced a survival rate similar to the survival rate of IL-2VCO+IFN-alpha was VCO+IL-2 + IFN-alpha (survival rate was 67%). The cause of the prolonged survival with the IL-2VCO+IFN-alpha treatment was identified as the reduction of CC-36 hepatic metastases (mean liver weight 1.31 g and mean tumor nodules 2). This reduction was significant when compared to IL-2VCO (1.58 g and 11), VCO+IFN-alpha (1.96 g and 53), and IFN-alpha (2.24 g and 91) treatments. The mechanism of the induction of antitumor response by the VCO+IL-2+IFN-alpha treatment was analyzed by measuring the direct cytotoxic activity of IFN-alpha on CC-36 tumor cells and by measuring the induction of cytolytic T-cell activity against CC-36 tumor cells. Results suggest that IFN-alpha produced minimal direct cytotoxic activity against CC-36 cells; however, the IL-2VCO+IFN-alpha combination therapy induced an enhanced cytolytic T-cell activity against CC-36 tumor cells (85.1% at E:T 100:1) when compared to other treatments (IL-2VCO 26.3%, VCO+IFN-alpha 13.4%, and IFN-alpha alone 6.3%). In addition, the role of T-cell subsets for the induction of antitumor immune response was analyzed in a survival study that used CD8-positive T cell-depleted mice. It was found that the survival rate was affected in mice depleted with CD8-positive T cells and treated with IL-2VCO+IFN-alpha when compared to control mice which had no T-cell depletion and were treated with IL-2VCO+IFN-alpha. This study suggests that the addition of IFN-alpha along with IL-2VCO increased the survival rate of mice having CC-36 hepatic metastases through the induction of CD8-positive T cells. Furthermore, this study confirms that IL-2VV can be used as a substitute for recombinant IL-2 in cytokine-augmented active specific immunotherapy.

Adenocarcinoma↗
PubMed1992

Active specific adjuvant immunotherapy with vaccinia melanoma oncolysate.

Vaccinia melanoma oncolysate is an investigative agent for active specific adjuvant immunotherapy. Viral oncolysate work in animals has led to application of this treatment in humans. Success of initial trials in treatment of melanoma has led to a phase III randomized, prospective, double-blind, multi-institutional trial, which is currently under way.

Adjuvants, Immunologic↗
PubMed1992

Prospects for gene therapy and lymphokine therapy for metastatic melanoma.

Conventional treatment of cancer, especially for patients with metastatic melanoma tumor, is often ineffective. Immunotherapy and recently introduced gene therapy have revolutionized the treatments of patients with metastatic melanoma tumor. Use of biological response modifiers, such as interleukins and interferons, have been found to enhance therapeutic benefits to patients with malignant melanoma. Initial studies with a high-dose interleukin-2 (IL-2) therapy have proved effective in patients with melanoma tumor, although a variety of systemic toxicities were observed. A low-dose IL-2 continuous infusion has shown a similar response in patients with melanoma tumor, but produced lesser toxicity. The low-dose IL-2 therapy has been studied with an adoptive transfer combined with either autologous lymphokine activated killer cells or autologous tumor infiltrating lymphocytes (TIL). IL-2 in combination with chemotherapeutic agents such as flavone acetic acid, dacarbazine, and cyclophosphamide have also been studied in patients with metastatic melanoma. Results have shown a moderate response in patients with metastatic melanoma. TIL therapy, however, has been shown to result in higher objective regression due to potent tumor-specific killing and tumor-specific targeting characters of the TIL. The tumor targeting nature of the TIL creates the possibility of using TIL as a vehicle to deliver gene product specifically to tumor tissue. Safety and toxicity of gene-transduced TIL were addressed by the use of neomycin-resistant, gene-transduced TIL in patients with metastatic melanoma. We also investigated the use of vaccinia oncolysate therapy by using the viral oncolysate prepared with IL-2 gene encoded vaccinia virus. Preliminary studies with murine hepatic metastases colon model have shown encouraging results.

Animals↗
PubMed1992

Active specific immunotherapy with vaccinia melanoma oncolysate.

Based on antitumor effects observed with vaccinia virus infected tumor cell lysate in animal models, adjuvant immunotherapeutic clinical trials were undertaken in patients with melanoma using vaccinia virus infected melanoma oncolysate (VMO). Preliminary clinical trials showed that the VMO is safe except minimal side effects such as mild fever, pain, and tenderness at the site of VMO injection, and mild lymphadenopathy. The effective dose of VMO was investigated in a following trial using 0.05 to 2.0 mg doses of VMO. Clinical responses and laboratory monitoring of melanoma-specific antibody responses decided the 2 mg dose of VMO is optimal for future trials. In all the clinical trials, patients showed moderate responses and their postimmune sera contained melanoma-specific antibodies. In a Phase II clinical trial completed August 1985 19 of 39 stage II patients had a disease-free mean survival time of 24.6 months, statistically significant compared with historical controls. Because of compelling evidence of significant clinical responses in patients treated with VMO adjuvant immunotherapy in the Phase II trial, a prospective randomized multi-institutional double-blind Phase III adjuvant VMO immunotherapeutic trial using adjuvant therapy of vaccinia virus alone as control, was recently initiated. Results of this trial are anxiously anticipated.

Humans↗
PubMed1990

Active specific immunotherapy with vaccinia colon oncolysate enhances the immunomodulatory and antitumor effects of interleukin-2 and interferon alpha in a murine hepatic metastasis model.

The role of cytokines as primary or adjuvant antineoplastic agents has been well established. Interleukin-2 (IL-2) and the interferons have, particularly, proven to be effective antitumor agents when given alone, and seem to act synergistically on the eradication of metastases from immunogenic tumors. Active specific immunotherapy, in the form of viral oncolysates, has also shown effectiveness in cancer therapy. Bearing this in mind, we decided to combine these agents in an adjuvant triple regimen and compare their effectiveness to other treatments in terms of tumor burden and survival in a murine colon cancer hepatic metastases model. BALB/c mice were injected with CC-36, a weakly immunogenic murine colon adenocarcinoma, intrasplenically, to produce artificial liver metastases. The animals were divided into one control group and seven treatment groups receiving either vaccinia colon oncolysate (VCO), IL-2, interferon-alpha (IFN alpha) alone, or combinations of these agents. Half the animals were followed for survival and the other half were sacrificed at the end of the experiment for quantification of tumor burden. The blood of the sacrificed animals was utilized in a series of immunological tests in order to demonstrate the cytolytic potential of the peripheral blood lymphocytes (PBL) in each treatment group, as well as to characterize phenotypically the cells acting as effectors. The triple-adjuvant regimen group was by far the most effective treatment group, demonstrating 100% survival and a significant reduction in tumor burden when compared to other groups. Furthermore, the PBL from the animals in this group showed 69.4% lysis of the CC-36 target cells in vitro. These effector lymphocytes were characterized as ASMG1-/Lyt2.2+ cytolytic lymphocytes. We conclude that these lymphocytes were stimulated by the administration of VCO and further augmented by the immunomodulation of the cytokines given in the triple regimen, and that such a regimen might prove beneficial in the treatment of established hepatic metastases from weakly immunogenic tumors.

Adjuvants, Immunologic↗
PubMed1990

The use of state-of-the-art mammography in the detection of nonpalpable breast carcinoma.

Between November 4, 1984, and September 1, 1988, a total of 16,439 patients were evaluated at the Comprehensive Breast Center at Mount Sinai Medical Center (MSMC) of Miami Beach with clinical examination, state-of-the-art mammography, and, when indicated, complimentary ultrasound mammography. As a result of this, 547 patients had open surgical biopsy, 207 carcinomas were detected in 207 patients, 183 carcinomas (80% of total malignancies) were clinically occult and detected only with breast imaging. Since 207 malignancies were found out of 547 areas examined, our rate was 1 carcinoma in every 2.6 biopsies. One hundred seventy-nine malignant lesions had preoperative needle localization and specimen radiography. Eighty-seven (47%) clinically occult carcinomas were identified because of microcalcifications by mammography alone. Two hundred twenty-six (98%) of the carcinomas were called malignant or suspicious for malignancy with only three (2.4%) false negatives. Twenty-two (10%) patients had axillary lymph-node metastasis. While recent large series report a 15 to 30 per cent rate of carcinoma for nonpalpable, mammographically detected breast biopsy specimens, it is our experience at MSMC with the use of physical exam and mammography, complemented by ultrasound when indicated, that rates of detection of carcinoma are more significantly improved than what the recent literature suggests; therefore, our approach to achieve this better detection will be discussed.

Adult↗