Early treatment of severe mandibular hypoplasia with distraction mesenchymogenesis and bilateral free fibula flaps.

The technique of distraction has revolutionized the treatment of mandibular hypoplasia; however, presently large mandibular defects still require bone grafts. Microvascular grafting is commonly used in adults. Conversely, in pediatric reconstruction, nonvascularized rib grafts remain standard. Unfortunately, resorption of nonvascularized bone remains a major issue, particularly when soft tissue is hypoplastic. This case study represents a combination of techniques in the treatment of severe mandibular deficiency, and introduces the concept of distraction mesenchymogenesis. The patient was a 2 1/2-year-old boy with severe bilateral Pruzansky class III mandibular hypoplasia. He had a permanent open mouth posture, an overjet of 23 mm, and was unable to move the lower mandibular segment. His oropharyngeal airway diameter was 2.2 mm and he was tracheostomy dependent. The patient was treated with distraction of the lower jaw mesenchyme followed by bilateral functional free fibular microvascular flaps containing reinnervated muscle. This created a well-vascularized body, ramus, and condyle bilaterally within an adequate soft-tissue envelope. Postoperatively, the overjet was reduced to 5 mm. The patient can now actively move his mandible. Airway diameter increased to 10 mm, and the patient is able to tolerate intermittent tracheostomy plugging. This innovative combination of techniques allows early intervention, limits graft resorption, and improves airway control.

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.

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.

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)

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.