Treatment of primary CLL cells with bezafibrate and medroxyprogesterone acetate induces apoptosis and represses the pro-proliferative signal of CD40-ligand, in part through increased 15dDelta12,14,PGJ2.

B-cell chronic lymphocytic leukemia (CLL), the most common leukemia in older adults, remains largely incurable and novel treatments are urgently required. We previously reported powerful pro-apoptotic actions of bezafibrate (BEZ) and medroxyprogesterone acetate (MPA) against Burkitts lymphoma cells. Here, we demonstrate that BEZ and MPA individually, and more potently when combined (BEZ+MPA), induce apoptosis of unsorted and CD19(+ve)-selected CLL cells and abrogate the pro-proliferative activity of CD40(L). This action was tumor cell specific, as the drugs had little impact on normal donor cells. The antiproliferative actions of BEZ+MPA were associated with the generation of reactive oxygen species (ROS), and the proapoptotic actions were associated with the generation of both ROS and mitochondrial superoxide (MSO). BEZ increased prostaglandin D(2) (PGD(2)) synthesis by CLL cells, and treatment with PGD(2) and its antineoplastic derivative 15dDelta(12,14,)PGJ(2) recapitulated BEZ-induced antiproliferative and proapoptotic actions. The PGD(2) receptor antagonist, BW868C, did not block BEZ or PGD(2) activity against CLL cells. The potency of BEZ+MPA against CLL cells mirrored that of chlorambucil, and BEZ+MPA combined with chlorambucil was more potent than either treatment alone. Given the known safety profiles of BEZ and MPA, our data warrant further investigation of their potential as novel therapy for CLL.

Flexible esophagoscopy as part of routine panendoscopy in ENT resident and fellowship training.

We conducted a retrospective study to evaluate the use of flexible esophagoscopy as part of routine panendoscopy in an academic setting. We reviewed the results of 378 procedures that were performed over a 4-year period in an academic otolaryngology--head and neck surgery program for residents and fellows. Medical records were reviewed for early and late complications as well as for adequacy of the examination. We found no immediate or long-term complications associated with flexible esophagoscopy. Adequate examination was achieved in all but two cases (99%), both of which involved patients who had significant strictures related to radiation therapy and who were not able to be evaluated by rigid esophagoscopy. We conclude that flexible esophagoscopy is a safe and accurate means of evaluating the esophagus during a panendoscopic evaluation of the upper aerodigestive tract, and that it should be included in the diagnostic armamentarium of every otolaryngology--head and neck surgery resident and fellow.

Sphenoid sinus mucocele: a rare complication of transsphenoidal hypophysectomy.

Only seven cases of a sphenoid mucocele occurring after transsphenoidal hypophysectomy have been previously reported in the world literature. In this article, we report a new case, which occurred in a 67-year-old man. The sphenoid sinus mucocele developed 12 years following transsphenoidal hypophysectomy and adjunctive radiotherapy. The patient was successfully managed with incision and drainage. Although transsphenoidal hypophysectomy is a common operation, this particular complication appears to be rare or at least under-reported. Sphenoid sinus mucocele deserves consideration in the differential diagnosis of a sphenoidal parasellar mass in a patient who has undergone an earlier transsphenoidal hypophysectomy.

The optimum method for reconstruction of complex lateral oromandibular-cutaneous defects.

BACKGROUND: Ablation of large intraoral cancers can create extensive through-and-through defects of the lateral face, resulting in loss of external facial skin, the lateral and anterior mandible, and the lateral mouth. Repair requires reconstruction of the lips, mandible, and full-thickness cheek defects. Ideal reconstruction with vascularized composite free flaps requires adequate bone and sufficiently large, yet versatile, skin flaps capable of resurfacing extensive intraoral and external defects. METHODS: A series of 12 patients with large lateral facial-mandibular defects is reviewed. All patients were treated for squamous cell carcinoma except for 1 patient with osteoblastic sarcoma of the mandible. All patients underwent primary reconstruction with various free flap techniques, including 6 scapular free flaps, 2 iliac crest free flaps, 3 free fibula flaps, and 1 radial forearm flap. Attainment of reconstructive goals, free flap survival, and complication rates were assessed. RESULTS: All defects were successfully reconstructed in the primary setting. No flap failures occurred. One venous occlusion was successfully salvaged. No orocutaneous fistulas or postoperative hematomas were noted. CONCLUSION: The reconstructive options for extensive defects of the lateral face and jaw are reviewed with attention to the complex three-dimensional soft tissue requirements. The superiority of the scapular composite flap is emphasized because this single free flap provides two independent and versatile skin paddles of optimal thickness in addition to adequate bone stock.

Technical modifications of the latissimus dorsi pedicled flap to increase versatility and viability.

OBJECTIVE: Describe the elevation and insetting of the pedicled latissimus dorsi musculocutaneous flap. Review history of this flap's evolution and personal series of 68 consecutive cases since 1984. STUDY DESIGN: Retrospective review. SETTING: Tertiary, referral, academic center. METHODS: Retrospective review of 68 consecutive patient records in which the pedicled latissimus dorsi musculocutaneous flap was used to reconstruct head and neck defects. Overall flap survival and postoperative complications were used as outcome measures. RESULTS: Thirty-one women and 37 men underwent reconstruction with the latissimus dorsi pedicled flap between 1984 to 1998. The mean age was 61 years. Sixty-three cases followed postoncologic ablation and 5 cases addressed traumatic tissue loss. Forty-three patients had prior radiotherapy and 26 patients had undergone prior reconstructive surgery. The overall flap survival rate was 67/68 (98.5%), with one case of complete flap necrosis. Six cases of partial flap necrosis occurred. There were 8 other minor complications including fistula, wound dehiscence, hematoma and cerebrospinal fluid accumulation. Fifty-six donor sites were closed primarily resulting in 2 dehiscences and 17 seromatas. Three of 12 skin grafts to the donor sites were compromised. CONCLUSION: The excellent flap survival rate (98.5%) is the result of proper patient selection and adherence to three technical fundamentals: skin paddle design, pedicle dissection, and pedicle stabilization. The minimal donor site morbidity also demonstrated in this series supports the continued use of the latissimus dorsi pedicled flap for reconstruction of head and neck defects.

Straight midline mandibulotomy revisited.

OBJECTIVE: Describe recent experience with a simplified modification of the traditional mandibulotomy approach. STUDY DESIGN: Retrospective chart review. METHODS: Charts were reviewed retrospectively for 17 consecutive patients who underwent this approach over a 3-year period as a part of treatment for oral and oropharyngeal malignancies. RESULTS: No cases of bony nonunion, plate exposure, or other complications related to the mandibulotomy occurred in the postoperative phase. CONCLUSIONS: The modified straight midline mandibulotomy approach is simple and provides safe access for the treatment of oral and oropharyngeal tumors while minimizing postoperative morbidity.

Lateral thigh free flap for head and neck reconstruction.

OBJECTIVES: To present the technique of lateral thigh free flap reconstruction in the head and neck and review the use of this procedure in 58 head and neck defect reconstructions. STUDY DESIGN: Retrospective review in the setting of a tertiary, referral, and academic center. METHODS: Retrospective review of patient records in cases of lateral thigh free flap reconstruction for head and neck defects. Records were reviewed for patient age, gender, pathologic findings, type of reconstruction (pharyngoesophageal, glossectomy, oropharyngeal, or external soft tissue defects), recipient and donor-site complications, and flap failure. RESULTS: Fifty-eight patients underwent lateral thigh flap reconstruction from 1984 to 1997. Patient age ranged from 10 to 76 years. Thirty-nine patients were men, and 19 were women. Forty-three flaps were used for pharyngoesophageal reconstruction, nine for glossectomy defects, two for oropharyngeal defects, and four for external, soft tissue defects. All resections were for squamous cell carcinoma, except one case of recurrent hemangiopericytoma. One flap failure occurred from venous thrombosis (1.7%). Forty-two of 43 pharyngoesophageal defects were successfully reconstructed (97.6%). Five temporary salivary leaks were noted, but no frank fistulas occurred. One fistula occurred in the oropharyngeal reconstruction group. Four minor donor-site complications were noted (6.9%). CONCLUSION: This series demonstrates the low donor-site morbidity, as well as the reliability and versatility, of the lateral thigh free flap for head and neck reconstruction.

Quality of life assessment in patients undergoing head and neck surgery as evaluated by lay caregivers.

OBJECTIVES/HYPOTHESIS: Rehabilitation following head and neck cancer surgery has steadily moved into the outpatient realm and become dependent on caregivers with no formal medical background (lay caregivers.) Satisfactory rehabilitation and quality of life (QOL) depend on successful relationships between patients and the lay caregivers. This study evaluates the QOL assessments of patients by themselves and their primary lay caregivers before head and neck surgery. STUDY DESIGN: Institutional Review Board-approved study using validated QOL assessment instrument. MATERIALS AND METHODS: The preoperative QOL status in 50 patients undergoing extensive head and neck surgery was evaluated using the self-administered Medical Outcomes Survey Short Form 36 (SF-36). The patient's primary lay caregiver (spouse, child, or friend) completed a similar questionnaire evaluating the patient's status. RESULTS: Thirty-three (66%) questionnaires were returned. Twenty-five (50%) questionnaire sets were successfully completed by both parties and employable for comparison. Sixty percent of the caregivers were within the 90% confidence interval of the patient's assessment for six or more of the eight parameters evaluated by the SF-36. Likewise, caregiver assessments for specific parameters were consistently congruent with patient evaluation, except for the parameters of bodily pain and general health, for which caregivers demonstrated a trend for overrating pain and underestimating general health. Caregivers of the same generation as the patient demonstrated significantly higher congruence (P = .007). Similarly, a trend for higher congruence was noted in patients with recurrent disease. CONCLUSIONS: The importance of the lay caregiver has increased in the era of greater outpatient rehabilitation. This pilot study indicates that QOL assessment by lay caregivers may be examined with existing instruments and highlights QOL parameters critical to both the head and neck surgery patient and his or her primary lay caregiver.

Synovial sarcomas of the head and neck: MR findings.

OBJECTIVE: MR images of six synovial sarcomas of the head and neck were evaluated to determine their characteristic sites of origin, size, extent, intensity, and contrast enhancement. It was hoped that specific MR characteristics could be defined to suggest this entity. CONCLUSION: A nonmucosal head and neck mass that is isointense to gray matter on T1-weighted images and is well defined yet heterogeneous, with septations, hemorrhage, cysts, calcification, or multilocularity, should raise suspicion of a synovial sarcoma. Because the appearance of synovial sarcomas varies and other masses may appear similar, no specific imaging characteristics define the entity.

Heterotopic brain in the pterygopalatine fossa.

Heterotopic brain outside the cranial vault is uncommon. It occurs most frequently in the nasal region, although rests elsewhere in the aerodigestive tract have been reported. We describe a case of heterotopic brain in the pterygopalatine fossa.

Oxygenation and blood volume changes in flaps according to near-infrared spectrophotometry.

OBJECTIVE: To test the ability of near-infrared spectrophotometry (NIRS) to predict vascular compromise in flaps postoperatively. DESIGN: Pilot study. SUBJECTS: Eleven denervated latissimus dorsi flaps were assessed in 8 pigs. INTERVENTIONS: Flaps were isolated on their vascular pedicle. We used NIRS to demonstrate tissue oxygen saturation and quantities of deoxygenated hemoglobin and oxygenated hemoglobin when flaps underwent venous or arterial occlusions. Oxygen saturation (percentage of oxygenated hemoglobin) was calculated as the difference between the 2 light intensities (860-750 nm) with the use of 2 time periods: preoperative (80%) oxygen saturation and during arterial occlusion (0%) oxygen saturation with NIRS. Blood volume changes within the flap were also measured. RESULTS: Arterial occlusion resulted in significant decreases in oxygen saturation and in blood volume with immediate recovery. Venous occlusion resulted in an initial rapid increase in blood volume with no appreciable early deoxygenation. CONCLUSIONS: Near-infrared spectrophotometry appears promising as a noninvasive, low-cost, portable bedside monitor that can demonstrate in real time changes in blood volume and oxygen saturation within a flap at a variety of tissue depths.

Primary malignant melanoma of the sinonasal cavity: MR imaging evaluation.

To evaluate the magnetic resonance (MR) imaging characteristics of primary malignant melanoma of the sinonasal cavity, T1- and T2-weighted MR images of 12 patients with primary sinonasal melanoma were retrospectively reviewed. Gadolinium-enhanced imaging was performed in seven cases. The MR images were compared with histopathologic results. There were seven melanotic melanomas and five amelanotic melanomas; hemorrhage was present in three melanotic and two amelanotic melanomas. The seven melanotic melanomas were hyperintense to gray matter on T1-weighted images (whether hemorrhage was present or not), consistent with the paramagnetic effect of melanin. Four of the five amelanotic melanomas had intermediate signal intensity on T1-weighted images; one was not detected. On T2-weighted images, all of the melanomas detected had intermediate though variable signal intensity compared with that of gray matter. On gadolinium-enhanced images, all cases demonstrated mild to moderate enhancement. The signal intensity of sinonasal melanoma appears to vary according to the histopathologic components of the tumor. High signal intensity within the lesion on T1-weighted images suggests the presence of melanin.

Head and neck reconstruction.

Reconstructive procedures of the head and neck aim to repair soft tissue and bony defects while restoring optimal function and cosmesis. Defects necessitating reconstruction may be the result of congenital anomalies, destructive disease processes, trauma, or surgery. Because primary wound closure is often impossible in these settings and healing by secondary intention provides unacceptable appearance and function, tissues from elsewhere in the body are usually mobilized to achieve the reconstructive goals. Reconstructions using tissue grafts and flaps have unique characteristics on postoperative imaging that differ from the original tissues being replaced, as well as the appearance of the donor size prior to transposition. As these reconstructive techniques become more sophisticated, it is crucial that physicians have an appreciation for current reconstructive methods.

Cervical thorium dioxide granuloma ('thorotrastoma').

An elderly woman had an expanding cervical mass that entrapped and compressed the adjacent cranial nerves, blood vessels, and muscles. The mass was dense on radiographs, extended from the skull base to low neck in the prevertebral and parapharyngeal tissues, and showed mixed intensity on MR. A previous direct carotid arteriogram with thorium dioxide as the contrast agent suggested the histologically proved diagnosis of a cervical thorium dioxide granuloma ("thorotrastoma").