John F. Carew

Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi-mutated herpes simplex virus type-1 (G207)

G207 is a multi‐mutated, replication‐competent type‐1 herpes simplex virus designed to target, infect, and lyse neurological tumors. This study examines the feasibility of using G207 in the treatment of human colorectal cancer and defines the biological determinants of its antitumor efficacy. This virus was tested on five human colorectal cancer cell lines in vitro to determine efficacy of infection and tumor cell kill. These results were correlated to measures of tumor cell proliferation. In vivo testing was performed through direct injections of G207 into xenografts of human colorectal cancer tumors grown in flanks of athymic rats. To evaluate an alternate method of administration, hepatic portal vein infusion of G207 was performed in a syngeneic model of liver metastases in Buffalo rats. Among the five cell lines tested, infection rates ranged between 10% and 90%, which correlated directly with S‐phase fraction (8.6%–36.6%) and was proportional to response to G207 therapy in vitro (1%–93%). Direct injection of G207 into nude rat flank tumors suppressed tumor growth significantly vs. control (0.58 ± 0.60 cm3 vs. 9.16 ± 3.70 cm3, P<0. 0001). In vivo tumor suppression correlated with in vitro effect. In the syngeneic liver tumor model, portal infusion resulted in significant reduction in number of liver nodules (13 ± 10 nodules in G207‐treated livers vs. 80 ± 30 nodules in control livers, P<0.05). G207 infects and kills human colorectal cancer cells efficiently. In vitro cytotoxicity assay and tumor S‐phase fraction can be used to predict response to treatment in vivo. This antineoplastic agent can be delivered effectively by both direct tumor injection and regional vascular infusion. G207 should be investigated further as therapy for colorectal cancer and liver metastases.—Kooby, D. A., Carew, J. F., Halterman, M. W., Mack, J. E., Bertino, J. R., Blumgart, L. H., Federoff, H. J., Fong, Y. Oncolytic viral therapy for human colorectal cancer and liver metastases using a multi‐mutated herpes simplex virus type‐1 (G207). FASEB J. 13, 1325–1334 (1999)

Selective Infection and Cytolysis of Human Head and Neck Squamous Cell Carcinoma with Sparing of Normal Mucosa by a Cytotoxic Herpes Simplex Virus Type 1 (G207)

This study evaluates inhibition of human squamous cell carcinomas (SCCs) by a replication-competent multimutated herpes simplex virus type 1 (G207). Infectivity and cytotoxicity of the G207 virus were evaluated in vitro in seven human SCC cell lines. In vivo effects of the G207 virus on human tumor xenografts in an athymic rat model were then investigated by injecting established tumors with 1 x 10(7) virus particles and monitoring tumor growth. In addition, oral cavity tumors in immunocompetent hamster were infected with the G207 virus by selective intraarterial perfusion and the tumor response was monitored. In vitro studies demonstrated infection rates, measured 24 hr after exposure, exceeding 40% at an MOI of 2 in five of seven human SCC cell lines. Cytotoxic effects, as measured by percent cell death on day 5, exceeded 90% in five of seven SCC cell lines. In vivo inhibition of tumor growth in an athymic rat model was seen (p < 0.005) and in two of the cell lines a complete clinical response was seen in 12 of 14 tumors. In the hamster model, selective intraarterial perfusion with G207 virus showed selective infection of the tumor cells, with sparing of the adjacent normal mucosa, which leading to significant suppression of tumor growth (p < 0.005). The G207 virus displayed efficient and selective cytotoxicity and tumor growth inhibition against human SCC and may prove useful as a therapeutic agent for head and neck SCC.

Hemangiopericytoma of the head and neck

Objective/Hypothesis: Hemangiopericytomas are uncommon neoplasms of vascular origin that may arise in the head and neck. Their rare occurrence and variable malignant potential have limited attempts to characterize their clinical behavior. This study reviews the experience in treating hemangiopericytomas of the head and neck at a single institution.

Treatment of recurrent pleomorphic adenomas of the parotid gland

Recurrent pleomorphic adenomas (RPAs) of the parotid gland are an uncommon but challenging problem. The records of 31 patients with RPAs were reviewed to assess the clinical presentation and treatment results. More than half of these patients underwent total parotidectomy. Local control was achieved in 94% of patients at 7 years (median follow-up 7.3 years). Patients who had surgery for recurrence after a formal parotidectomy were more likely to have another recurrence (63% local control at 7 years) than patients whose initial procedure was a limited excision (100% local control at 7 years; P < 0.01). Better local control was seen in 11 patients who received postoperative irradiation (100% at 10 years) than in 20 patients who did not (71% at 10 years; P < 0.28). Adequate surgical resection yields an acceptable local control rate in patients with RPAs. Postoperative radiation therapy may improve control in patients at high risk for another recurrence.

Current trends in pediatric tracheotomy

A retrospective analysis was performed on 103 pediatric patients, less than 5 years of age, undergoing tracheotomy at New York Hospital between 1980 and 1990. Charts were reviewed with respect to primary diagnosis, indication for tracheotomy, duration of the tracheotomy, complication rate and mortality rate. Approximately 62% of the tracheotomies were performed in patients less than 12 months of age, with the most common indication being an acquired or congenital airway abnormality. The number of patients receiving tracheotomies for neurological disorders, however, increased more than threefold over the course of this review. Approximately one-third of the patients experienced immediate, early or delayed complications. There was a significant correlation between the complication rate and weight at the time of the tracheotomy as well as the degree of prematurity of the child. Over one half of the infants under 2000 g suffered complications. A mortality rate of 2.9% was noted in our study with mucous plugging of the tracheotomy being the most common etiology of death.

Effects of Scalpel, Electrocautery, and CO2 and KTP Lasers on Wound Healing in Rat Tongues

Objective: Evaluate wound healing of incisions created by the scalpel, electrocautery, CO2 laser, and potassium titanyl phosphate (KTP) laser in the upper aerodigestive tract in an animal model.

Predictive Value of Facial Nerve Electrophysiologic Stimulation Thresholds in Cerebellopontine-Angle Surgery†

The predictive value of intraoperative stimulation thresholds for facial nerve function, using a constant‐current system, was examined in 49 patients undergoing resection of cerebellopontine‐angle tumors. Immediately after surgery, 75% of the 0.1‐mA threshold group, 42% of the 0.2‐mA group, and 18% of the 0.3‐mA or greater group had good (grade I or II) facial nerve function. One year after surgery, 90% of the 0.1‐mA group, 58% of the 0.2‐mA group, and 41% of the 0.3‐mA or greater group had grade I or II function.

Delayed epistaxis resulting from external carotid artery injury requiring embolization: a rare complication of transsphenoidal surgery: case report.

OBJECTIVE AND IMPORTANCE Delayed epistaxis resulting from trauma to branches of the external carotid artery is an infrequent but potentially serious complication of transsphenoidal surgery. We report two cases of severe, delayed epistaxis in patients who had undergone transsphenoidal surgery. In both cases, noninvasive treatment failed, necessitating endovascular intervention. CLINICAL PRESENTATION The first patient, a 52-year-old woman with a prolactinoma, underwent a second transsphenoidal resection 18 months after the first surgery. She was readmitted on postoperative Day 15 with massive epistaxis. The second patient, a 40-year-old woman, had undergone two transsphenoidal surgeries, 14 years apart, for an adrenocorticotropic hormone-secreting adenoma. She was readmitted with massive epistaxis on postoperative Day 17. INTERVENTION Both patients were initially treated with nasal balloon packing but experienced recurrent hemorrhage when the balloon was deflated, necessitating referral to the interventional radiology department for embolization. At arteriography, the first patient was found to have a pseudoaneurysm of the medial branch of the left internal maxillary artery, which was subsequently embolized. Arteriography in the second patient revealed an abnormally dilated midline branch of the right internal maxillary artery in the nasal septum; this vessel was occluded at arteriography. CONCLUSION Delayed massive epistaxis is a rare but significant complication of transsphenoidal surgery. Injury to branches of the external carotid artery, along with injury to the internal carotid artery, should be suspected in patients who present with delayed epistaxis after transsphenoidal surgery. Angiography performed in patients with refractory bleeding should include selective external carotid injections. Epistaxis that is refractory to anterior and posterior nasal packing may be effectively treated with endovascular embolization.

Management options for cerebrospinal fluid leak after vestibular schwannoma surgery and introduction of an innovative treatment.

Objective: To review the management of cerebrospinal fluid leak after vestibular schwannoma removal reported in the literature and to present a novel approach to management of recalcitrant cases. Data Sources: MEDLINE and PubMed literature search using the terms “cerebrospinal fluid leak” or “cerebrospinal fluid fistula” and “acoustic neuroma” or “vestibular schwannoma” covering the period from 1985 to present in English. A review of bibliographies of these studies was also performed. Study Selection: Criteria for inclusion in this meta-analysis consisted of the availability of extractable data from studies presenting a defined group of patients who had undergone primary vestibular schwannoma removal and for whom the presence and absence of cerebrospinal fluid leakage was reported. Studies reporting combined approaches were excluded. No duplications of patient populations were included. Twenty-five studies met the inclusion criteria. Data Extraction: Quality of the studies was determined by the design of each study and the ability to combine the data with the results of other studies. All of the studies were biased by their retrospective, nonrandomized nature. Data Synthesis: Significance (p < 0.05) was determined using the χ2 test. Conclusions: Incisional cerebrospinal fluid leakage responded well to local management and lumbar drainage. Rhinorrhea often necessitated surgical intervention. No specific reoperation techniques correlated exclusively with better reoperation outcomes. The transaural/transnasal approach presents an alternative for surgical management of cerebrospinal fluid rhinorrhea.

Advances in multimodality therapy for laryngeal cancer.

Combined induction chemotherapy and external beam radiation therapy is an effective treatment for selected patients with advanced-stage laryngeal cancer. The larynx can be preserved in two-thirds of patients receiving this treatment. Investigations continue to evaluate the ideal treatment regimen, the delivery of chemotherapy, patient selection, biologic markers predicting response, functional outcome, and the effectiveness of this treatment at other sites.