Biomedical subjects
Publications and source records attributed to R L Fabian.
With the advent of the antibiotic era, the incidence of osteomyelitis has decreased remarkably. However, cases of trauma-induced orbital cellulitis, abscess, fistula formation, and osteomyelitis may still occur. The following case is illustrative of the chronicity of problems (8-year course) caused by retained orbital wooden foreign bodies.
At the Dana-Farber Cancer Institute Head and Neck Cancer Clinic, 114 previously untreated patients with advanced squamous cell carcinoma of the head and neck (17% stage III; 83% stage IV) were managed with induction chemotherapy using cis-platinum, bleomycin, and methotrexate, followed by definitive extirpative surgery and/or radiation therapy. The present report evaluates this group from a surgical and surgical pathology standpoint. The following aspects are evaluated: predictability of, and conversion to, resectability during induction chemotherapy; ease of surgical technique and intraoperative assessment; patterns of pre-op and post-op risks and complications; gross and histopathologic observations of the extent and character of residual primary and nodal disease, particularly after a response to chemotherapy; patterns of locoregional control or failure related to treatment variables. The issues subsequently addressed include: how does chemotherapy affect the operative candidacy and resectability of proposed surgical patients? Could, or should surgery be eliminated in the management of some patients treated with induction chemotherapy? Can less radical surgery be contemplated in patients significantly "downstaged" by prior chemotherapy treatment? Is increased locoregional or distant metastatic control observed in these patients? What is the role of surgery in the responder to chemotherapy?
One hundred consecutive patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with induction combination chemotherapy followed by definitive surgery and/or radiotherapy, and were evaluated for radiotherapy related toxicity. The induction regimen consisted of cisplatin, bleomycin and methotrexate/leucovorin. Acute toxicity consisted predominantly of mucositis and weight loss, and was mild or moderate by degree in 94% of patients. Six percent of patients experienced severe or life threatening acute toxicities. Two acute toxic deaths were noted in this series, one from a combination of mucositis, weight loss and infection and one from hypoglycemia of unknown origin. Thirty-five percent of patients had radiation treatment interrupted briefly because of acute toxicity. Toxicity was greatest in patients who were nonresponders to induction chemotherapy and such may have been related to the continued presence of advanced tumor. Radiotherapy dose, surgical intervention and age did not have an impact on the presence or degree of acute toxicity. Late toxicities included: hypothyroidism in 32% of patients tested: osteoradionecrosis in 5% of patients, associated primarily with a composite resection (4 of 5 cases); and soft tissue ulcerations in 3%. Taken together, these data indicate that induction combination chemotherapy did not significantly increase the toxicity of subsequent radiotherapy with or without surgery.
Between Oct 1, 1979 and Aug 1, 1982, 93 patients with advanced squamous carcinoma of the head and neck were given neoadjuvant treatment with cisplatin, bleomycin sulfate, and methotrexate before standard local treatment. Ninety-three patients were evaluable for response. The response rates were as follows: complete response, 24%; partial response, 64%; and no response, 12%. Differences in primary tumor site, performance status at presentation, histologic grade, and tumor size did not correlate with response to this chemotherapy. For patients achieving notable tumor reduction to 2 cm or less, standard local treatment with either surgery plus radiotherapy or high-dose radiotherapy alone was effective in controlling local disease. For patients with larger tumor masses following neoadjuvant chemotherapy, surgical resectability appeared to improve local control rates. In our series, patients not receiving maximal standard local treatment often had relapse of local disease despite favorable responses to chemotherapy.
The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.
The historical evolution of reconstruction of the cervical esophagus and laryngopharynx over the past 100 years is documented. The impact of these technical achievements is contrasted to the failure to improve the 5-year survival rate of 24%. While the clinician awaits new protocols of treatment to improve survival statistics, the thrust of the surgical oncologist is to develop a reliable method of reconstruction which meets specific minimal criteria. The following objectives should be achieved: Reconstruction should not limit the effectiveness of the ablative technique. Short hospitalization and one stage techniques are superior. Technique mortality and morbidity must be low. A 10-year institutional study using the Montgomery 2-stage technique is presented. In contrast, comparative literature data analysis of all methods of laryngopharyngocervical reconstruction indicates that single stage techniques offer a greater advantage. This study suggests that visceroplasty (stomach), free jejunal transfer, and single stage reconstruction, using the pectoralis myocutaneous flap, approach the previously established criteria more effectively than others. A new technique (1-stage), using partial tubulation of the pectoralis major myocutaneous flap, is recommended for regional reconstruction of the cervical esophagus and pharynx. In order to decrease the pressure and torsion on the vascular pedicle of the pectoralis major myocutaneous flap and increase its predicted length, partial resection of the ipsilateral clavicle is proposed.
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Four cases of primary small cell carcinoma of the larynx are described. Two patients presented with extensive metastatic disease and two with tumor limited to the larynx. All four cases responded (3PR, 1CR) to systemic combination chemotherapy. Long-term remission was achieved in one patient with limited disease who underwent chemotherapy with a complete response followed by definitive radiotherapy. Treatment results are compared with previously reported cases. The importance of early diagnosis through staging, and combined treatment in small cell carcinoma of the larynx is discussed.
Fourteen patients with advanced salivary gland malignancies were treated with combination chemotherapy. Five of 13 patients responded to cyclophosphamide and adriamycin and two patients in the responding groups underwent further potentially curable treatment, rendering them disease-free. Three patients with mucoepidermoid carcinoma failed to respond to this regimen, but two of three patients treated with a combination of cisplatinum, bleomycin and methotrexate responded. The potential role for chemotherapy in the treatment of salivary gland malignancies is discussed.
A combined modality regimen employing induction chemotherapy with cisplatinum, bleomycin and methotrexate followed by surgery and/or radiation therapy was initiated in patients with advanced squamous cell carcinoma of the head and neck. In the first 23 patients treated with this program there was a 90% response rate to induction chemotherapy (9% CR and 81% PR). Toxicity associated with radiotherapy, but not surgery, was increased with 11 of 23 patients (48%) who experienced some toxicity during or immediately after radiotherapy. Mucositis was worse than expected and severe delayed mucositis was seen in 2 patients, one or whom required hospitalization. Late complications, possibly related to therapy included one myocardial infarction and one episode of hypoglycemia, both of which were fatal. One other patient voluntarily failed to take prescribed oral leucovorin, dying of unrescued methotrexate toxicity during adjuvant therapy, a questionable suicide. Further follow-up and analysis of failure will be necessary to determine if the value of a combined modality regimen in producing an increased cure rate and long term survival will out weight increased toxicity.
Optimal therapy for stage III and stage IV squamous carcinoma arising in the head and neck requires a multidisciplinary approach, including chemotherapy. Advances have identified several chemotherapeutic agents and combinations of agents that show substantial antitumor activity in this disease. While antitumor activity can be documented, experience indicates the duration of antitumor effect is short, and the toxicity may limit further therapy. To date, studies have not shown an advantage of combination chemotherapy over single agents. Theoretically, combination chemotherapy should increase patient survival through regression of the primary tumor as well as ablation of distant metastases. An analysis of recent trials with patients who received induction chemotherapy before definitive local treatment suggests that regression of tumor in stage III and stage IV lesions before definitive therapy may increase local treatment for regional disease. Randomized trials are needed to confirm or disprove the efficacy of combination chemotherapy for advanced squamous carcinoma of the head and neck.
A diagnosis of undifferentiated carcinoma by light microscopy in a neck node biopsy is insufficient to come to a conclusive answer as to the type of tumor with which one is dealing. The fact that undifferentiated carcinoma by light microscopy may very well be a histiocytic lymphoma with a different mode of treatment and an increasingly improved cure rate has changed the mode of evaluation in arriving at a diagnosis of the node in the neck with no visible primary in the upper aerodigestive tract.
Myocutaneous flap reconstruction in the head and neck represents a significant surgicall advance. Careful preoperative evaluation, a clear understanding of rehabilitative physiology, and application of the appropriate surgical technique will result in meaningful restoration and consistent success.
Seventy-five percent of carotid-cavernous sinus fistulae result from high velocity head trauma. The most common symptom is a pulse synchronous bruit which usually becomes apparent when the patient regains his sensorium. The objective manifestations of such an arteriovenous fistula are characteristically localized to the ipsilateral orbit. A periorbital bruit and venous engorgement of the palpebral and bulbar conjunctivae are pathognomonic features. Bilateral carotid angiography confirms the diagnosis and determines which of several techniques might be used to obliterate the fistula. Occasionally the classic signs and symptoms may be delayed for days or weeks. Thus, the maxillofacial surgeon must be aware of this clinical entity to avoid untimely repair of facial fractures with potentially disastrous consequences.
A florid case of dermal cylindroma is presented as representative of the natural history and usual clinical findings in a patient afflicted by this tumorous growth. Although histologically and clinically benign, dermal cylindroma can result in considerable disfigurement of the patient. Treatment varies from isolated primary resection to serial resections with subsequent electrocautery or cryosurgery for small recurrences. Total scalping with skin grafting is reserved for only the most severe cases where normal integument has been completely involved by the disease process.
Resection of intermediate-sized (T2 and T3) lesions of the anterior floor of the mouth is often associated with defects in speech, glutition, and cosmesis despite reconstructive efforts. This paper describes the use of the central island myomucosal tongue flap to reconstruct defects of this size. Since this flap possesses the same vascular characteristics as the myocutaneous flap it offers similar advantages. Experience with seven patients in whom this flap was used suggested that this is a dependable method of anterior floor of mouth reconstruction since there was no evidence of nonviability, delayed healing, or wound breakdown. The advantages of this flap are: (a) it is rapidly developed from easily accessible local tissue, (b) it offers the same reliability as myocutaneous flaps, (c) it causes less disability of articulation and deglutition than other tongue flaps, and (d) it results in no cosmetic deformity.
A pulsed ultraviolet excimer laser was used to ablate bone in vitro at 193, 248, 308, and 351 nm and in vivo at 193 nm. Ablation was dependent on sufficient fluence (energy delivered per unit area per pulse) for plasma formation at the target site at all wavelengths. Adjacent tissue damage at various fluences for each wavelength was examined using a light microscope. Damage was minimal at 193 nm (1 to 3 microns) and most extensive at 351 nm (60 to 75 microns). This is in sharp contrast to the 1 to 3 mm of adjacent thermal damage produced when carbon dioxide lasers are used to ablate bone. Differences in the degree and type of damage to adjacent tissues among the wavelengths studied indicated that other ablation mechanisms and tissue interactions are involved in addition to simple plasma vaporization of bone. Bleeding during and after ablation demonstrated that the use of this laser does not cause thermal damage, which would cauterize adjacent vessels. Pre- and post-mortem lesions made at identical power and pulse settings were of equal depth, indicating that bleeding does not affect the ablation rate. The excimer laser has potential as a microsurgical instrument for the precise removal of bone with minimal damage to adjacent structures.
Chemotherapy as initial treatment for advanced squamous carcinoma has received much recent attention. Despite sparse experimental data supporting its usefulness, such chemotherapy is now used for a variety of advanced malignancies. This experience is conceptually reviewed, with special emphasis on squamous carcinoma of the head and neck. Factors which influence treatment results, such as drug dosage, radiation treatment planning, and surgical resection, will require careful analysis in the evolution of the multidisciplinary approach to advanced head and neck cancer.