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Biomedical subjects

M K Wallack

Publications and source records attributed to M K Wallack.

At least 55 records · Page 3Linked to original sources

Management of the pregnant patient with carcinoma of the breast.

The diagnosis of carcinoma of the breast during pregnancy poses a challenging dilemma. Although once regarded as incurable, recent reports reveal similar long term survival rates for pregnant and nonpregnant patients who have carcinoma of the breast. When referred to a surgeon, a pregnant woman with a suspicious mammary mass deserves an expedient histologic diagnosis; delay may jeopardize the chances of survival. Once the diagnosis is established, pregnant patients should be treated in a manner similar to nonpregnant patients because there is no evidence that carcinoma of the breast in pregnant women is biologically different than carcinoma of the breast in other premenopausal women. Fears of fetal exposure to radiation should not deter a physician from ordering appropriate preoperative diagnostic tests to stage the patients. Operation may be performed safely when general anesthesia is administered and postoperative adjuvant therapy should be administered when necessary. The involvement of multiple subspecialties in the management of these patients is highly recommended.

Abnormalities, Radiation-Induced↗

Crohn's disease of the appendix.

Crohn's disease limited to the appendix is uncommon. The disease may mimic acute appendicitis with fever, leukocytosis, right lower quadrant pain, and occasionally a palpable mass. When Crohn's disease affects the appendix, it typically has a longer clinical period in which the patient has symptoms than do most cases of acute appendicitis. The most common preoperative diagnoses are acute appendicitis and appendiceal abscess. A review of the literature is presented along with our experience in three additional cases of Crohn's disease limited to the appendix. We suggest that Crohn's disease be included in the preoperative differential diagnosis and that extensive intraoperative examination of the gastrointestinal tract be made in any case of suspected appendicitis that has had a protracted preoperative course.

Adolescent↗

Vaccinia virus-infected C-C36 colon tumor cell lysates stimulate cellular responses in vitro and protect syngeneic Balb/c mice from tumor cell challenge.

Vaccinia virus (VV) was used to infect and lyse the Balb/c colon tumor line C-C36 to prepare oncolysate (VCO) with augmented immunogenicity. Mice treated with VCO and challenged with C-C36 were significantly protected against tumor growth as compared to untreated controls (P less than 0.001) and mice treated with CO (P less than 0.01). Moreover, protection induced by VCO was specific when growth inhibition of C-C36 was compared to that of meth-A (P = 0.027). Splenocytes from mice stimulated with VCO in vitro showed greater proliferation than splenocytes stimulated with CO alone or VV alone, suggesting induction of a unique VCO component. Additional evidence for a specific response was suggested by the observation that splenocytes stimulated with VCO in vitro demonstrated augmented cytolysis of C-C36 but did not show cytolytic activity against unrelated target cells. However, augmented cytolysis of the natural killer (NK)-sensitive YAC-1 by VCO-stimulated splenocytes was also observed. These results suggest that in vivo resistance to tumor challenge induced by VCO treatment may result from stimulation of both specific and nonspecific effector cells.

Adenocarcinoma↗

Improvement in disease-free survival of melanoma patients in conjunction with serologic response in a phase Ia/Ib Southeastern Cancer Study Group trial of vaccinia melanoma oncolysate.

Thirty-nine patients with malignant melanoma who were disease-free after surgery but at high risk for recurrence were treated with vaccinia melanoma oncolysate (VMO) for 12 months. Clinical results, after a mean follow-up of 17 months showed that 25 of 39 patients had no evidence of disease. Comparison of disease-free survival of patients in this study with that of 39 matched controls from other adjuvant trials shows statistically significant advantage of VMO therapy. Evaluation of serological responses of patients undergoing VMO treatment by an enzyme-linked immunosorbant assay (ELISA) showed a positive correlation between IgG antibody binding to cultured melanoma cells and disease-free survival.

Clinical Trials as Topic↗

Melanoma patient antibody responses to melanoma tumor-associated antigens defined by murine monoclonal antibodies.

Sera from melanoma patients undergoing immunization with three distinct immunogens were evaluated for development of IgG antibody specific for the melanoma tumor-associated antigens (TAAs) GD3 and 250-kd glycoprotein (high molecular weight; HMW). Of 99 patients receiving either irradiated allogeneic melanoma cells admixed with bacillus Calmette-Guérin, vaccinia viral oncolysate melanoma cell membranes, or cholesterol hemisuccinate-modified melanoma cells, 12 were determined to have responded against GD3 and 17 against the HMW TAA. This reactivity was measured using both direct binding to purified TAA and specific inhibition of binding of murine monoclonal antibodies R24 and Me-1-14 for GD3 and HMW TAA, respectively. Preimmune sera from these patients did not react with these TAAs, nor did preimmune sera or follow-up sera from melanoma patients electing not to receive immunotherapy. These results suggest that melanoma patients can be immunized against these TAAs as presented on the melanoma cell membrane in an immunotherapy setting and that immunization using purified TAAs might likewise be feasible.

Animals↗

Treatment of murine hepatic metastases with vaccinia colon oncolysates and IL-2.

To evaluate the feasibility and utility of vaccinia colon oncolysates (VCO) and low-dose interleukin-2 (IL-2) immunotherapy for advanced colon cancer, we have developed a murine model and tested the efficacy of combined treatment regimens. We employed intrasplenic injection of cultured colon adenocarcinomas (C-C36) in syngeneic Balb/c mice to produce experimental hepatic metastases. In the first set of experiments, animals were challenged with 5 X 10(5) tumor cells and sacrificed 14 days following tumor challenge. In the second set of experiments, animals were challenged with 2 X 10(5) tumor cells and followed for survival over the ensuing 90 days. In the first set of experiments, animals were treated prophylactically with VCO (40 micrograms, sc, 14 and 7 days prior to challenge) and/or therapeutically with IL-2 (25,000 u, Hoffmann-LaRoche rIL-2, ip BID, on Days 1-3 following challenge). In the second set of experiments, animals were treated with either the identical regimens or therapeutically with VCO (same dose, sc, 2 and 10 days following challenge) and/or IL-2 (same dose, ip BID, on Days 9-11 following challenge). Tumor burden data from sacrificed animals was in agreement with survival data and showed significant tumor burden reduction in the combined treatment group as assessed by liver weight and tumor nodule enumeration. Survival data demonstrated highly significant survival advantage for animals treated with the two biological response modifiers: VCO (P less than 0.0021), and IL-2 (P less than 0.0017). The data presented suggest a synergistic effect for these two agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Cholecystectomy in the elderly.

A 4-year retrospective review of 212 patients over 70 years of age who underwent elective and emergency cholecystectomies was undertaken. Elective procedures were performed in 119 patients (76 women, 43 men) whereas 93 patients (43 women, 50 men) underwent emergency surgery. Complications developed in 25 and 34 patients, respectively. In the elective group, the most common complication involved the cardiovascular system, whereas sepsis with multiple organ failure accounted for all of the deaths in the emergency group. Among the 212 patients studied, there was a 3 percent mortality rate in the elective group and a 10 percent mortality rate in the emergency group, with an overall mortality rate of 6 percent. The results indicated that since the risks of elective cholecystectomy are relatively low in the elderly and the risks of cholecystectomy performed as an emergency are considerably higher (10 percent), symptomatic elderly patients with gallstones should be considered good candidates for early elective cholecystectomy.

Aged↗

Vaccinia colon oncolysate immunotherapy for murine hepatic metastases can be modulated with low-dose interleukin-2. Third place winner: Conrad Jobst Award.

A murine colon cancer hepatic metastases model was developed via intrasplenic injection of C-C36 tumor cells in syngeneic Balb/c mice to determine the potential efficacy of vaccinia colon oncolysate (VCO) immunoprophylaxis and therapy with and without low-dose interleukin-2 (IL-2) immunomodulation. Mice were injected with 40 micrograms VCO subcutaneously, either prophylactically or therapeutically. IL-2 (Hoffman-La Roche, Nutley, NJ) was administered at a dose of 25,000 units intraperitoneally twice daily for three consecutive days, prophylactically, therapeutically immediately after tumor challenge (early), or 9 days after tumor challenge (late). Mice were followed for 50 days after tumor challenge, and mortalities were recorded. Mice receiving VCO alone did not demonstrate better survival than controls. However, mice receiving VCO with IL-2 immunomodulation demonstrated consistently better survival than mice treated with IL-2 alone or controls. The group receiving VCO therapy with late IL-2 modulation (75% survival demonstrated improved survival over controls (0% survival, P less than 0.00001), VCO-treated mice (0% survival, P less than 0.005), and IL-2-treated mice (29% survival, P = 0.07). In vitro assays revealed enhanced NK activity and suggested cytotoxic T-lymphocyte (CTL) induction as possible mechanisms responsible for these biologic effects. Combined VCO and IL-2 immunotherapy may be of potential benefit to patients with metastatic colon cancer, but further research is required to optimize treatment regimens.

Animals↗

Cholecystectomy in the elderly.

A two-year retrospective review of 137 patients over 70 years of age undergoing cholecystectomy, from January 1, 1983 to January 1, 1985, was done at Mount Sinai Medical Center of Miami Beach. This study focused on the clinical presentations, surgical management, and overall morbidity and mortality of this operative procedure in the elderly. There were 81 women and 56 men in the study ranging in age from 70 to 96. Elective procedures were performed in (78/137) 57 per cent of the patients while (59/137) 43 per cent underwent emergency surgery. Elective procedures were performed in (55/81) 68 per cent of the women and (23/56) 41 per cent of the men. Emergency surgery was required in (26/81) 32 per cent of the women and (33/56) 60 per cent of the men. Complications developed in (16/78) 20 per cent of the elective cases and (19/59) 32 per cent of the emergency cases. In the elective group, the most common complication involved the cardiovascular system. Sepsis with multiple organ failure accounted for all the deaths in the emergency group. Among the 137 patients in this series, there was a (3/78) 3.8 per cent mortality in the elective group and a (7/59) 12 per cent mortality in the emergency group with an overall mortality of (10/137) 7.3 per cent. The purpose of this study was to highlight the necessity for aggressive surgical management of biliary tract disease in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Positive relationship of clinical and serologic responses to vaccinia melanoma oncolysate.

In this phase Ia/Ib trial, vaccinia melanoma oncolysate (VMO) is a virus-augmented melanoma cell membrane vaccine that has been shown to be safe and to stimulate the production of antimelanoma antibodies in high-risk melanoma patients treated in a surgical adjuvant setting. One patient with stage I and 38 patients with stage II melanoma were entered in the study between December 1984 and October 1985, with a mean follow-up of approximately 17 months. Each patient received a smallpox booster injection followed one week later by the first of 13 weekly intradermal injections of 2.0 mg of VMO. At the end of 13 weeks, injections were given every other week for 12 months or until recurrence. Clinical results show that 25 of the 39 patients had no evidence of disease as of December 1986. Moreover and more importantly, statistical comparison of patients in this study with 39 matched controls shows a significant increase in disease-free survival for the patients treated with VMO. Serum obtained prior to treatment and at three-month intervals during treatment was tested in a Staphylococcus protein A rosette assay for reactivity with melanoma cell lines. All pretreatment samples (39/39) were negative, and 64% became positive by 12 months after appropriate dosage escalations. Moreover, enzyme-linked immunosorbent assay showed a positive correlation between anti-melanoma IgG antibody titer and disease-free survival.

Adult↗

Serological evaluation of melanoma patients in a phase I/II trial of vaccinia melanoma oncolysate (VMO) immunotherapy.

Vaccinia melanoma oncolysates (VMO) were tested in a Southeastern Cancer Study Group (SECSG)-sponsored phase I/II multiinstitutional trial. Forty-eight patients with stage I or II disease were placed on study at six different dose levels of VMO and two different dose schedules, immediate or delayed. Patients' sera, obtained before treatment and every 3 months following initiation of treatment, were tested for antimelanoma antibodies using a Staphylococcus protein A (SpA) assay. Pretreatment sera were negative in 46 of 47 patients, and only two of 19 patients on delayed treatment developed reactivity by 6 months. However, 13 of 23 on immediate treatment developed reactivity, including eight of eight at the higher doses (1.5 and 2.0 mg). Neither anti-HLA antibody tested by a standard microcytotoxicity assay nor circulating immune complexes measured by both Clq and conglutinin binding assays were produced as a result of the immunization. The demonstration of immunogenicity of VMO at the 2 mg dose and immediate schedule supported the rationale for the use of this dose and schedule for the ongoing second phase Ia/Ib trial and for the future phase III randomized prospective study.

Antigen-Antibody Complex↗

Gastric cancer in the elderly.

The surgical treatment of gastric cancer in the elderly (over 65 years of age) was retrospectively studied in the department of surgery, at the Mount Sinai Medical Center, Miami Beach, Florida. The authors found 22 patients who were operated on for gastric cancer between 1979 and 1982. Ages ranged from 69 to 90 years of age. The male-to-female ratio was 1:1. Twenty of 22 patients were found to have carcinoma. Eleven of 20 had regional spread to the perigastric nodes, transverse colon, omentum, spleen, and liver. Stage of disease was: stage I--four patients, stage II--five patients, stage III--eight patients, and stage IV--three patients. Two of 22 patients had lymphoma. The mean hospital stay was 17.1 days, but decreased to 12.4 days if no complications occurred. Postoperative complications were minimal and included pneumonia, urinary tract infection, wound infection, and dumping syndrome. There were two postoperative deaths (9%) due to sepsis and myocardial infarction, respectively. Six of the remaining 18 patients died within 1 year. Seven of 18 were alive after 2 years, and six patients survived greater than 36 months (33%). Of the six long-term survivors, two had stage III and one had stage IV disease at the initial exploration. The average survival was 23.5 months. The authors conclude that gastric resection should not be withheld in the elderly. The elderly have the same morbidity and mortality from surgery for gastric cancer as patients under age 65.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

A Southeastern Cancer Study Group phase I/II trial with vaccinia melanoma oncolysates.

Vaccinia melanoma oncolysates (VMO) were tested in a Southeastern Cancer Study Group (SECSG) Phase I/II trial. Forty-eight patients with high-risk Stage I or pathologic Stage II disease were placed on study at six different dose levels and two different treatment regimens. Patients were monitored for toxicity to the VMO after each injection. Patients' sera were tested for anti-human melanoma reactivity with the Staphylococcus Protein A (SpA) assay. Toxicity was minimal at all doses tested. In only 2 of 19 patients on delayed treatment did reactivity develop in the SpA assay by 6 months. However, 13 of 23 patients on immediate treatment showed reactivity, including 8 of 8 at the two highest doses. Since the VMO appears to be safe at all of the doses tested, and because of the immunogenicity of the VMO at the higher doses as demonstrated by the SpA assay, the 2-mg dose level, for immediate treatment, was chosen for use in future trials.

Adolescent↗

Gastric epithelioid leiomyoma causing intraperitoneal hemorrhage.

We have presented a rare and interesting case of intraperitoneal hemorrhage due to an epithelioid leiomyoma, the second such case in the literature. Epithelioid leiomyomas are usually clinically insignificant. When hemorrhage occurs, it is usually intraluminal and rarely intraperitoneal. Ultrasonography, upper gastrointestinal series, and computerized tomography are important tools in the diagnosis of complicated gastric tumors. Wedge resection is generally recommended, but subtotal gastrectomy should be considered if malignancy is suspected.

Aged↗

A phase I/II SECSG (Southeastern Cancer Study Group) pilot study of surgical adjuvant immunotherapy with vaccinia melanoma oncolysates (VMO).

Forty-eight patients with nonrecurrent high risk Stage I and II malignant melanoma were treated with Vaccinia Melanoma Oncolysates (VMO). Six different dose levels and two different treatment regimens were tested. Thirty-two out of 48 patients completed the 12 months of therapy. Side effects were mild to moderate. Twenty-eight out of 48 patients remain free from disease with a mean survival of 19 months, while 20/48 patients have recurred with a mean time to recurrence of 6 months.

Adjuvants, Immunologic↗

Survival after malignant melanoma in a black child. A case report and review of the literature.

A malignant melanoma of clinical and pathologic State I but deep microstage that occurred on the lower extremity of a prepubertal black male child, who is free of recurrence 3 years following surgical excision, regional node dissection, and BCG adjuvant immunotherapy, is reported. Previously described cases of malignant melanoma in black children indicate that it is a rare and virulent lesion, since all patients expired due to their tumors within 6 months. The judicious use of principles derived from management of adults with such lesions may prolong survival and disease-free interval in this patient population.

BCG Vaccine↗

Serologic response to human melanoma lines from patients with melanoma undergoing treatment with vaccinia melanoma oncolysates.

Specific active tumor immunotherapy methods offer the possibility of increasing the immunogenicity of tumor cells. One of these methods is viral oncolysis, in which tumor cells are modified by viral infection. We prepared vaccinia melanoma oncolysates (VMO) from human melanoma lines infected with vaccinia virus. In a preliminary trial at Washington University, sera from 12 patients with melanoma with stage I and II disease were obtained before and during treatment with VMO. The reactivity of these sera to melanoma lines was examined with a Staphylococcus protein A assay that detects most human IgGs. Our data demonstrate that, during treatment with VMO, sera from all 12 patients developed reactivity to melanoma lines. Selected sera were also tested in a double blind study by the C3-mixed hemadsorption assay, which detects mostly IgM. Results from this assay were in complete agreement with those obtained by the Staphylococcus protein A assay: Pretreatment sera were generally negative and sera obtained during treatment were positive. The specificity of these responses is presently under investigation. Our findings indicate that, as a consequence of treatment with VMO, a reactivity develops in the patients' sera. This reactivity is probably due to both IgG and IgM antibodies and its directed toward antigens expressed on human melanoma lines.

Adult↗