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Biomedical subjects

W R Panje

Publications and source records attributed to W R Panje.

At least 73 records · Page 4Linked to original sources

Free omental flap reconstruction of complicated head and neck wounds.

Complicated wounds of the head and neck involve a severe deficiency of tissue in a contaminated or irradiated area that is predisposed to infection and necrosis. Reconstruction of these wound areas frequently requires multiple operations and prolonged hospitalization. We have successfully reconstructed complicated head and neck wounds in thirteen patients by means of a single-stage microvascular tissue transfer of the greater omentum with or without an attached segment of the stomach wall. There were 11 complete successes, two partial failures, and no complete failures. We describe four cases to illustrate the basic fundamentals of this reconstructive technique.

Adult↗

Hydroxyurea, fluorouracil, and concomitant radiotherapy in poor-prognosis head and neck cancer: a phase I-II study.

Hydroxyurea and fluorouracil (5-FU) are active cytotoxic drugs in head and neck cancer and have shown synergistic activity in vitro. Both drugs also act as radiosensitizers. Therefore, we administered radiotherapy at daily fractions of 180 to 200 cGy with simultaneous continuous infusion 5-FU at 800 mg/m2/d and escalating daily doses of hydroxyurea for five days. Cycles were repeated every other week until completion of radiotherapy. Thirty-nine inoperable patients were treated at six dose levels of hydroxyurea ranging from 500 mg to 3,000 mg orally daily. Little effect of hydroxyurea on the WBC or platelet count was noted in patients receiving less than 2,000 mg daily, whereas both parameters decreased progressively in patients receiving 2,000 mg daily or more. Mucositis occurred at all dose levels, requiring frequent dose reduction of 5-FU; however, in patients receiving a daily hydroxyurea dose of 2,000 mg or less, the median weekly 5-FU dose administered was 1,725 mg/m2 (86% of the intended 5-FU dose), whereas at daily hydroxyurea doses exceeding 2,000 mg, the median weekly 5-FU dose decreased to 1,133 mg/m2 (57%) (P = .001). Of 15 evaluable patients with recurrent disease after prior local therapy only one failed to respond; six had a complete response (CR), and eight a partial response (PR). Of 17 evaluable patients without prior local therapy, 12 had a CR, with no patient developing recurrence in the irradiated field to date; five patients had a PR. We conclude that the recommended dose of hydroxyurea in this regimen is 2,000 mg daily. That dose will cause mild to moderate myelosuppression and will allow for delivery of greater than 80% of the intended 5-FU dose. The activity of this regimen in poor-prognosis head and neck cancer exceeds 90%; its further investigation in previously untreated patients is warranted.

Adult↗

Neoadjuvant and adjuvant methotrexate, cisplatin, and fluorouracil in multimodal therapy of head and neck cancer.

To increase the complete response (CR) rate of patients with locally advanced head and neck cancer after three cycles of neoadjuvant chemotherapy, we added sequential methotrexate to the combination of cisplatin and continuous infusion fluorouracil (5-FU). We also evaluated the feasibility of administering three additional cycles of the same regimen as adjuvant chemotherapy. Thirty-eight patients were treated; the median age was 53 years and 36 patients had stage IV disease. Chemotherapy consisted of methotrexate 120 mg/m2 followed 24 hours later by cisplatin 100 mg/m2 and a five-day continuous infusion of 5-FU at 1,000 mg/m2/d. Of 34 patients evaluable for response to neoadjuvant chemotherapy, nine had a CR, 21 a partial response (PR), two a minimal response (MR), and one patient each stable disease (SD) and no response (NR). Of 31 patients who received local therapy, 15 were treated with surgery and radiotherapy and 16 with radiotherapy alone. Of 25 patients eligible to receive adjuvant chemotherapy only ten received all three intended cycles, while 15 received less or no adjuvant chemotherapy because of patient refusal, cumulative toxicity, or early disease progression. With a median follow-up time of 39 months, the median survival is estimated to be 20 months. Of eight patients with nasopharyngeal or paranasal sinus cancer, none has had disease recurrence. Patients with good initial performance status and low N-stage also had a significant survival advantage. Chemotherapy-related toxicities consisted mainly of mucositis, requiring 5-FU dose reduction in the majority of patients; similar toxicities were exacerbated in the adjuvant setting. The addition of methotrexate did not increase the CR rate over what has been reported for the combination of cisplatin and 5-FU alone. Certain subsets of patients appear to have a good prognosis when treated in this fashion. The administration of adequate adjuvant chemotherapy in patients with head and neck cancer remains difficult due to toxicity and poor patient compliance.

Adolescent↗

Facial reanimation by XI-VII anastomosis without shoulder paralysis.

Transposition of the spinal accessory (XI) and facial (VII) nerves has been used successfully in reanimation of facial paralysis, but because of the severity of symptoms associated with denervation of the trapezius muscle, this technique has largely been abandoned. Hypoglossal-facial (XII-VII) nerve anastomosis has now become a more favored procedure; however, the resultant hemiglossal atrophy carries some morbidity. Transposition of the sternocleidomastoid (SCM) branch of the accessory nerve as a way to avoid shoulder paralysis was reported more than 20 years ago with initially excellent results, yet few follow-up studies have been done. Twenty-one fresh cadaver dissections of the accessory nerve-SCM branch and facial nerve were performed to determine if adequate numbers of fascicle groups and sufficient proximal nerve length are available for an adequate end-to-end anastomosis without nerve interposition grafting. This paper presents our anatomic and histologic findings to support the use of proximal SCM nerve anastomosis to distal facial nerve in facial reanimation. When feasible, the use of this technique to correct facial paralysis is encouraged rather than hypoglossal-to-facial nerve anastomotic repair.

Accessory Nerve↗

Murine subrenal capsule assay: prediction of chemoresponsiveness in head and neck cancer.

If chemotherapy is to be used with the greatest efficacy in head and neck cancer, a predictive test that will indicate tumor sensitivity or resistance in individual patients may be desirable. This report demonstrates that the in vivo murine subrenal capsule assay was an efficient, sensitive method for retrospectively predicting the clinical response of squamous cell carcinomas of the head and neck to chemotherapy. Twenty-five courses of chemotherapy in 22 patients were compared to responses in the in vivo assay. The assay correctly identified sensitivity to chemotherapy in 86% of clinically responding patients. The specificity of the assay was 78%. A 60% efficiency for predicting clinical response and a 93% efficiency for predicting clinical resistance were demonstrated. Eighty percent of the results were correctly classified. The murine subrenal capsule assay has potential in planning of chemotherapy for selected patients.

Adult↗

A porcine model for multiple musculocutaneous flaps.

The purpose of this study was to develop and describe in detail a reproducible porcine model for musculocutaneous flap study. The model was required to demonstrate the following: 1. consistent, easily identifiable anatomical landmarks for muscles and muscular vascular pedicles; 2. flap survival, consistent with the musculocutaneous perforator arrangement of blood supply; 3. ease of islanded- or free-flap formation; 4. arrangement of flaps on each animal, allowing paired studies of control and experimental flaps; and 5. a maximum number of flaps per animal, without undue morbidity or mortality. Pilot dissections were made of the pectoralis, trapezius, latissimus dorsi, gracilis, biceps femoris, and tensor fasciae latae muscles and their major vascular pedicles. After establishing the anatomical landmarks, we formed musculocutaneous flaps at each site to verify the above five requirements. A total of 72 muscle/vessel pedicle dissections were performed, incorporating formation of 61 island musculocutaneous flaps. The skin component overlying an islanded muscle block survived in 60 instances, confirming the reliability of the flap model. We concluded that five pairs of musculocutaneous flaps could be fashioned on one pig, using the bilateral control/experimental paradigm if desired. The pectoralis, latissimus dorsi, trapezius, gracilis, and biceps femoris muscles were used. The ventral muscle group (pectoralis, gracilis) was raised in one operating session, and the lateral muscles (trapezius, latissimus dorsi, biceps femoris) were raised in one further session per side. Three new porcine flaps are described--the pectoralis, biceps femoris, and trapezius. Morbidity was confined to mild splinting of the limbs for one day. This is also the first example of the use of ten musculocutaneous island flaps on one pig, and represents an opportunity for performing physiological, pathological, or pharmacological experiments on the musculocutaneous flap.

Animals↗

Concomitant hydroxyurea, 5-fluorouracil, and radiation therapy for recurrent head and neck cancer: early results.

We tested the combination of hydroxyurea (HU), 5-fluorouracil (5-FU), and concomitant radiotherapy (XRT) in a group of patients with advanced or recurrent head and neck cancer. Both drugs are effective single agents, have shown synergistic activity in vitro, and can act as radiation sensitizers. A 5-day course of radiotherapy, with simultaneous HU and continuous infusion 5-FU, was followed by a 9-day rest period; cycles were repeated until completion of XRT. Sixteen patients have completed their therapy. Eleven patients had recurrent disease after previous therapy with surgery (11 patients), radiotherapy (9 patients), and combination chemotherapy (4 patients). Five patients had not received previous local therapy. These patients had persistent disease after induction chemotherapy and/or were inoperable because of poor general medical condition. Of 15 patients evaluable for response, 9 had complete response, including 5 patients who had earlier local therapy; 5 had partial response; and 1 failed to respond. Toxicities included mild myelosuppression and mucositis. No unusual complication related to previous radiotherapy was observed. This regimen has shown impressive activity in a cohort of patients who are not usually responsive to other types of currently available therapy. We are continuing our investigation to further define efficacy, toxicity, and maximally tolerated doses of this regimen.

Aged↗

Implantable venous access device: use in patients with advanced head and neck cancer.

As a result of prolonged hospitalizations and the frequent administration of sclerosing antibiotics and/or chemotherapeutic agents, vascular access frequently becomes difficult in patients with advanced head and neck carcinoma. Eighty-six totally implantable venous access devices were placed in 83 patients with advanced head and neck cancer to facilitate the administration of continuous intravenous infusion chemotherapy. Complications relating to surgical placement or usage of the device occurred in 29 of 86 ports (34%), leading to the removal of eight devices (9%). The implantation of two devices required revision. There were no serious sequelae from any of the complications. The port facilitated the administration of home chemotherapy in 11 patients. Because of our favorable experience, we now routinely recommend placement of these devices to all patients with advanced head and neck cancer at our institution.

Catheterization, Central Venous↗

Cisplatin, fluorouracil, and high-dose leucovorin for recurrent or metastatic head and neck cancer.

We added high-dose oral leucovorin to the combination of cisplatin and fluorouracil (5-FU) to assess the efficacy of this regimen in the treatment of patients with head and neck cancer. Cisplatin, 100 mg/m2, was followed by a 5-FU continuous infusion at 600 mg/m2/d for five days. Leucovorin, 50 mg/m2, was administered at the start of cisplatin and every six hours throughout the duration of the 5-FU infusion. The dose of 5-FU was escalated to 800 mg/m2 and 1,000 mg/m2 according to observed toxicity. In a second phase of the study, the dose of leucovorin was escalated to 50 mg/m2 every four hours. A total of 25 patients were registered: 23 had recurrent disease after extensive prior treatment; and two had newly diagnosed metastatic disease. The maximally tolerated dose of 5-FU was 800 mg/m2/d with leucovorin administered every six hours. Toxicities at that level included mild to moderate myelosuppression and dose-limiting mucositis in the previously irradiated field. Identical toxicities were observed when administering 800 mg/m2/d of 5-FU with leucovorin every four hours. Eighteen patients were evaluated for response: one had a pathologic complete response; nine had a partial response (including four who received prior cisplatin and 5-FU as induction chemotherapy); and eight patients failed to respond. The mean peak and trough plasma leucovorin concentrations were 2.61 (+/- 1.07) mumol/L and 2.46 (+/- 0.95) mumol/L with administration of the drug every six hours, and 2.75 (+/- 2.15) mumol/L and 2.52 (+/- 1.48) mumol/L with administration every four hours. We conclude that the combination of cisplatin, 5-FU, and leucovorin has activity in the treatment of recurrent head and neck cancer. The maximally tolerated dose of 5-FU in this study was 800 mg/m2/d, with mucositis in previously irradiated sites being dose-limiting. Plasma leucovorin concentrations exceeding 1 mumol/L are achieved following oral administration of this drug.

Adult↗

Osteochondroma presenting as a neck mass: a case report.

Osteochondromas are benign bone tumors which rarely present as neck masses. This report reviews the literature and presents the case of a 10-year-old girl with a neck mass and hoarseness due to an osteochondroma of the cervical spine. An extensive diagnostic evaluation and partial surgical excision were necessary. Although rare, osteochondromas should be considered in the differential diagnosis of a firm neck mass. Surgical excision of these lesions is recommended.

Cervical Vertebrae↗

Radiotherapy of the resected mandible following stainless steel plate fixation.

There is general concern among otolaryngologists that irradiation of a stainless steel prosthesis used in mandibular reconstruction may cause irradiation overdosage to adjacent tissues. A tissue-equivalent plastic/steel model, simulating the characteristics of a stainless steel, reconstructed mandible, was irradiated and measurements were made with a parallel plate ionization chamber. The results of our measurements show that irradiation of an implanted steel plate results in an overdosage (120%) "in front" and an underdosage (80%) "behind" the steel plate. The regions of overdosage and underdosage are 2 to 3 mm thick. The overall dose modification is greatly reduced when two opposing fields are used. We conclude that irradiation of a stainless steel, reconstructed mandible with a 6-mV photon beam through opposing fields does not significantly alter the amount of radiation delivered to surrounding tissues.

Bone Plates↗

Sequential administration of methotrexate, cisplatin, and 5-fluorouracil in multimodal therapy for locally advanced head and neck cancer.

Thirty-eight previously untreated patients with locally advanced head and neck cancer received three cycles of induction chemotherapy with methotrexate (120 mg/m2) followed by cisplatin (100 mg/m2) and a 5-day continuous infusion of 5-fluorouracil (1,000 mg/m2 per day). The response rate in 34 evaluable patients was 94%, with a complete response rate of 26%. Thirty-one patients underwent local therapy following induction chemotherapy, and 25 (81%) were rendered free of disease: 14 of 15 treated with surgery and radiotherapy and 11 of 16 treated with radiotherapy alone. At a median follow-up of 11 months, 8 patients have relapsed while the remaining 17 patients continue free of disease. The dose-limiting toxicity of chemotherapy was mucositis resulting in reduction of the 5-fluorouracil dose in 28 patients. This regimen is highly effective in inducing responses in patients with locally advanced head and neck cancer; 81% of the patients who complete local therapy are rendered free of disease with this multimodal approach. Due to short follow-up, the relapse rate, overall survival, and disease-free survival cannot yet be determined.

Adolescent↗

The trapezius myocutaneous flap. Dependability and limitations.

Many reports of the trapezius myocutaneous flap have centered on a single form of the flap. However, three distinct myocutaneous segments, the superior, the lateral island, and the extended island flaps, can be harvested from the trapezius muscle and its overlying skin. Fifty-five patients underwent reconstruction for head and neck defects using 56 trapezius myocutaneous flaps consisting of 28 superior, 24 lateral island, and four extended island flaps. The four vascular supplies of the trapezius muscle are discussed, with emphasis on the variable nature of the transverse cervical and dorsal scapular arteries. Major complications developed in two of 28 superior, five of 24 lateral island, and one of four extended island flaps. The superior flap, although the most dependable, has the most limited range of application. Both the lateral and extended island flaps have a broader range of clinical application, but their usefulness may be limited by previous neck surgery or occult neoplasm in the neck, as well as by the variable vascular supply. Due to the above limitations, 30% of our attempts to utilize the lateral island flap had to be aborted at the time of surgery and an alternate means of reconstruction used. The trapezius myocutaneous flaps are excellent reconstructive tools for selected defects.

Female↗

The free greater omental flap for treatment of mandibular osteoradionecrosis.

Osteoradionecrosis can involve the mandible following radical irradiation for treatment of oral cavity cancer. The radionecrosis of the mandible is often associated with severe intractable pain, local or extensive deformity, including pathologic fracture, orocutaneous fistula formation, and frequent loss of function. Treatment has ranged from analgesia and antibiotics to hyperbaric oxygen treatments to local or extensive sequestrectomies with partial or total mandibulectomy and restoration of tissue losses with unirradiated tissue. To our knowledge, this is the first report of the successful use of a free greater omental flap for immediate treatment of mandibular osteoradionecrosis and concomitant reconstruction. We found the omentum to be an excellent vascular bed that rapidly resolved the osteoradionecrosis and pain, promoted healing, and restored mandibular function with minimal discomfort to the patient.

Humans↗

Proliferative myositis of the masseter muscle.

The authors present a case of a 33-year-old white man with a 4-month history of a rapidly enlarging, tender, painful, circumscribed facial mass located in the masseter muscle. CT scan and fine needle aspiration cytology, coupled with clinical assessment, suggested the diagnosis of proliferative myositis. Curative intraoral excisional biopsy was done, thereby avoiding a parotidectomy incision and approach to the lesion. The pathology showed proliferative myositis. A review of the literature revealed 36 cases which indicated that proliferative myositis is a relatively rare etiology of a head and neck mass. Careful clinical, radiologic, and pathologic evaluations were required to make this unusual diagnosis and avoid any unnecessary facial mutilation in its treatment.

Adult↗

Use of temporalis muscle flaps in complicated defects of the head and face.

Large defects in the upper two thirds of the face, skull, and skull base pose challenging reconstructive problems. There are a number of applicable reconstructive techniques, all with various advantages and disadvantages, available to otolaryngologists-head and neck surgeons. One method, originally described in the late 1800s, was evaluated by us. Applications of the technique included reconstruction of large defects of the forehead, dura, and anterior skull base, closure of orbital defects, and soft-tissue augmentation of the face. Advantages of this reconstructive technique are the flap's proximity to the defects and its simplicity of execution.

Adult↗

Indomethacin-induced augmentation of lymphoproliferative responses in patients with head and neck cancer.

Augmentation of the phytohemagglutinin (PHA)-induced lymphoproliferation of peripheral blood mononuclear cells by indomethacin, a drug which blocks prostaglandin (PG) synthesis, was assessed in 37 patients with squamous cell carcinoma of the head and neck. Indomethacin enhanced the uptake of 3H-thymidine in stimulated cultures both from patients and normal individuals. However, because lymphoid cells from cancer patients were less reactive than those from normal controls, the proportionate increase in PHA-stimulated 3H-thymidine incorporation caused by indomethacin was greater in this population than in the normal population. The degree of enhancement induced by indomethacin did not correlate with the percent of esterase-positive mononuclear cells in the preparations. The amounts of PGE synthesized at 48 h by patients' or normal cells were similar. Cell populations that exhibited elevated levels of augmentation in the presence of indomethacin were approximately 3 times as sensitive to inhibition by 3 nM PGE2. The degree of augmentation detected in the presence of Ro-20-5720, which also prevents PG synthesis, was related to that produced by indomethacin. These results suggested that: the enhancing effect of indomethacin on lymphoproliferation in vitro was related to its inhibition of PG synthesis; and the sensitivity of lymphoid cells to inhibition by PGE2 was slightly, but significantly, increased in individuals with elevated augmentation values.

Adult↗