Coverage of skull base defects.

Successful reconstruction of the cranial base requires a knowledge of this complex anatomic area, a careful assessment of the defect, a healthy respect for the potential for ascending infection and meningitis, and reliable techniques to effectively contain the intracranial space with vascularized tissue. The first step in reconstruction is a secure dural repair, which must be covered by a healthy vascularized layer. The scalp contains galeal and pericranial flaps, which are usually incorporated into the reconstruction. Sometimes, along with local muscles such as the temporalis, these local tissues are all that is needed to complete the reconstruction. When the defects are larger and in irradiated beds, free tissue transfer has emerged as the most reliable method to bolster the dural repair.

Thrombolytic therapy: what is its role in free flap salvage?

Thrombolytic agents have been demonstrated to improve free flap salvage in animal models. However, clinical evidence regarding their efficacy has been scant. The authors reviewed their experience with flap salvage using thrombolytic therapy in 1,733 free flaps from February 1990 to July 1998. Patients with intraoperative pedicle thrombosis were excluded from this review. Forty-one of the 55 free flaps that were reexplored emergently were identified as having pedicle thrombosis. Of these 41 flaps, 28 free flaps were salvaged (flap salvage group, 68%) and 13 free flaps failed (flap failure group, 32%). Thrombolytic therapy (urokinase in 7 patients, tissue plasminogen activator in 1 patient) was used in six flaps in the flap salvage group and two flaps in the flap failure group. Statistical analysis demonstrated no difference between the two groups with regard to thrombolytic therapy. There was also no difference between the two groups with regard to use of systemic heparin (100-500 U per hour) at the time of pedicle thrombosis or with regard to whether Fogarty catheters were used. Smoking, preoperative radiotherapy, and the use of interpositional vein grafts during initial flap reconstruction had no impact on the outcome of flap salvage. The flap salvage group was reexplored at a mean of 1.5 days compared with the flap failure group, which was reexplored at a mean of 4.2 days (p = 0.007). Early detection of pedicle thrombosis remains the most important factor in the salvage of free flaps. Although these numbers are small and definitive statements cannot be made, the role of thrombolytic agents in free flap salvage requires further clinical evaluation.

Reconstructive management of cranial base defects after tumor ablation.

Successful reconstruction after cranial base tumor ablation is paramount in preventing potentially life-threatening complications. The purpose of this study was to evaluate experiences of cranial base reconstruction and to identify reconstructive management principles that may assist in achieving successful cranial base reconstruction. All cranial base reconstructions performed by the Department of Plastic Surgery at the University of Texas M. D. Anderson Cancer Center between January of 1993 and September of 1999 were reviewed. Analyses were performed to assess the impact of location of defect, type of reconstruction, type of dural repair, and history of preoperative radiation and chemotherapy on rates of complications, and patient survival. The 77 patients who underwent cranial base reconstruction after tumor ablation during the study period had a mean age of 52 years (6 to 84 years). The mean follow-up period was 28.7 months (1 to 76 months). Squamous cell carcinoma, the most common histopathologic type, was present in 24 patients (31 percent), and 35 patients (45 percent) presented with recurrent disease. Location of defects involved region I (anterior) in 31 patients (40 percent), region II (anterior-lateral) in 18 (23 percent), region III (lateral-posterior) in six (8 percent), and more than one region in 22 (29 percent). Reconstructive methods included free flaps in 52 patients (68 percent), temporalis muscle flaps in 14 (18 percent), pericranial flaps in eight (10 percent), and other local flaps (two galeal, one scalp) in three (4 percent). Of the 52 free flaps, 18 (35 percent) were used in region I, 14 (27 percent) in region II, six (12 percent) in region III, and 14 (27 percent) in defects involving more than one region. Of the 14 temporalis muscle flaps, 13 (93 percent) were used for defects involving regions I or II and one (7 percent) was used for a defect involving region III. Of the 11 pericranial and other local flaps, nine (82 percent) were used in region I, one (9 percent) in region II, and one (9 percent) in a combination of regions II and III. Complications occurred in 21 patients (27 percent): three total flap losses (4 percent), three partial flap losses (4 percent), two cerebrospinal fluid leaks (3 percent), two cases of meningitis (3 percent), two abscesses (3 percent), five cases of delayed wound healing (6 percent), two hematomas (3 percent), one wound infection (1 percent), and one cerebrovascular accident (1 percent). Overall survival was 77 percent at 2 years and 58 percent at 4 years. The type of reconstruction, location of defect, type of dural repair, and history of preoperative radiation and chemotherapy had no significant association with the incidence of complications. Neither the type of reconstruction nor the location of defect showed a significant effect on patient survival. In this experience, local flaps, such as pericranial or temporalis muscle flaps, are good choices for reconstruction of smaller anterior or lateral cranial base defects. For defects that require larger amounts of soft tissue, free flaps are appropriate. With proper patient selection, successful cranial base reconstruction can be performed with either local or free flaps with a low incidence of complications.

Comparison of cost for DIEP and free TRAM flap breast reconstructions.

A recent article by Kaplan and Allen suggested that deep inferior epigastric perforator (DIEP) flap breast reconstruction was less expensive than reconstruction performed with free transverse rectus abdominis musculocutaneous (TRAM) flaps. To test that hypothesis, a series of patients who had undergone unilateral breast-mound reconstruction by the first author using DIEP or free TRAM flaps between November 1, 1996, and March 30, 2000, were reviewed. Bilateral reconstructions and reconstructions performed by other surgeons in the department were excluded to eliminate all variables except the choice of flap. All hours in the operating room and days in the hospital until discharge were included. Early readmissions for the treatment of complications were included, as were the costs of the mastectomy in the case of immediate reconstructions, but late revisions and nipple reconstructions were not. The totals were then converted into resource costs in 1999 dollars, and the DIEP and free TRAM flap groups compared. There were 21 DIEP flaps and 24 free TRAM flaps in the series. In this series, there was no significant difference between the cost of DIEP and free TRAM flap breast reconstruction.

Malignant melanoma arising within a burn scar case report and review of the literature.

Burn scar carcinomas, also called Marjolin's ulcers, are uncommon tumors that arise from an antecedent burn. Most burn scar carcinomas are diagnosed about 30 years after the burn, and most are well-differentiated squamous cell carcinomas. We report a case in which a squamous cell carcinoma developed within a burn scar on the cheek and then a malignant melanoma arose within the burn scar after the squamous cell carcinoma had been excised. We also review the available literature on burn scar carcinoma, covering the demographics, pathogenesis, diagnosis, prognosis, and treatment of the disease. Given the multifocality of this disease process, we advocate aggressive resection of the entire burn scar, as well as the tumor, to prevent the development of further cancers within the wound.

MR imaging of the muscular component of myocutaneous flaps in the head and neck.

BACKGROUND AND PURPOSE: Myocutaneous flaps are commonly used for reconstruction in head and neck surgery. The purpose of this study was to characterize the MR imaging findings of the muscular component of these flaps, with an emphasis on enhancement patterns. Recognition of these imaging findings is important in differentiating postoperative changes from recurrent tumor. METHODS: MR studies were evaluated in 25 patients who had undergone 27 flap reconstructions after resection of a head and neck tumor. Twenty were free flaps and seven were pedicled rotation flaps, and a dominant component of all flaps was muscle. MR images were reviewed for signal intensity, enhancement characteristics, and morphology over a period of 7 to 79 months. RESULTS: On baseline postoperative images, 21 flaps showed moderate or intense enhancement of the muscular graft component relative to nonenhancing native muscle, three flaps showed mild enhancement, and three showed no enhancement. On follow-up images, 18 flaps that initially had intense enhancement showed persistent intense enhancement, and three showed decreasing enhancement. Two flaps with initial mild enhancement were unchanged on follow-up, and one became nonenhancing. None of the initially nonenhancing flaps subsequently enhanced. T1 signal intensity of muscular graft components was always isointense with normal muscle, whereas T2 signal intensity was variable and tended to be stable. Ninety-three percent of our muscular flap components showed striations typical of normal muscle and were best identified on T1-weighted images. No significant imaging differences were found between pedicled and free flaps. CONCLUSION: Most muscular flap components show moderate or intense enhancement on fat-suppressed contrast-enhanced MR images that may persist for many months and be quite striking. Radiologists should be familiar with the typical postoperative appearance of predominantly muscular flaps to avoid misdiagnosis as tumor extension or recurrence.

Incidence of hematoma associated with ketorolac after TRAM flap breast reconstruction.

Ketorolac is frequently used as an adjunct for postoperative pain relief, especially by anesthesiologists during the immediate postoperative period. It can be used alone as an analgesic but is more often used to potentiate the actions of narcotics such as morphine or meperidine in an attempt to reduce the total dose and side effects of those drugs. The manufacturer of ketorolac cautions against its use in patients who have a high risk of postoperative bleeding, for fear of increasing the risk of hematoma, but the risk in transverse rectus abdominis musculocutaneous (TRAM) flap patients has never been reported. In a study of 215 patients who had undergone TRAM flap breast reconstruction, it was determined that patients who received intravenous ketorolac (n = 65) as an adjunct to their treatment with morphine administered by use of a patient-controlled analgesia device required less morphine (mean cumulative dose, 1.39 mg/kg) than did patients who did not receive ketorolac (n = 150; mean cumulative dose, 1.75 mg/kg; p = 0.02). There was no increase in the incidence of hematoma in patients who were treated with ketorolac. The data presented in this study suggest that the use of intravenous ketorolac does reduce the need for narcotics administration in patients undergoing TRAM flap breast reconstruction, without significantly increasing the risk of hematoma.

Postoperative morphine requirements of free TRAM and DIEP flaps.

In a review of the charts of 158 patients who had undergone breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps and who were treated for postoperative pain with morphine administered by a patient-controlled analgesia pump, the total dose of morphine administered during hospitalization for the flap transfer was measured. Patients whose treatment was supplemented by other intravenous narcotics were excluded from the study. The mean amount of morphine per kilogram required by patients who had reconstruction with DIEP flaps (0.74 mg/kg, n = 26) was found to be significantly less than the amount required by patients who had reconstruction with TRAM flaps (1.65 mg/kg; n = 132; p < 0.001). DIEP flap patients also remained in the hospital less time (mean, 4.73 days) than did free TRAM flap patients (mean, 5.21 days; p = 0.026), but the difference was less than one full hospital day. It was concluded that the use of the DIEP flap does reduce the patient requirement for postoperative pain medication and therefore presumably reduces postoperative pain. It may also slightly shorten hospital stay.

Brachytherapy: reconstructive options and the role of plastic surgery.

The objectives of this study were to evaluate reconstructive methods for patients receiving brachytherapy after cancer ablation. This retrospective review evaluated 19 patients who received brachytherapy and reconstruction between 1991 and 1998. The average age of the patient was 61.9 years and the average follow-up was 2.9 years. Lesions were located in the upper extremity (N = 6), trunk (N = 2), and lower extremity (N = 11). In all patients, early postoperative brachytherapy was initiated 5 days after wound closure. The average radiation dose was 47 Gy (range, 45-50 Gy) and was delivered over a 3 to 5-day period. In each case, varying numbers of catheters were employed (average, 8 +/- 5 catheters). Free flap coverage was performed in 8 patients, and the latissimus dorsi was used most often. Pedicled regional flaps were employed in 11 patients (58%). Sixteen patients (84%) had additional external beam irradiation, and 10 patients (52%) underwent preoperative chemotherapy. All flaps survived with a demonstrated low complication rate (10%). In 2 patients, partial flap necrosis and infection occurred. Three donor site complications were observed and included wound dehiscence in 2 patients and hematoma in 1 patient. Cumulative effects of external beam radiation and brachytherapy did not affect the complication rate. Location of the defect did not alter the incidence of complications. Wound complications did not delay functional rehabilitation in these patients; however, hospital stay was longer. In 8 patients local recurrence occurred (42%) between 6 and 36 months after surgery whereas in 6 patients (32%) distant metastasis was observed. Ten patients are currently alive without evidence of disease. One of the most important concerns about early postoperative brachytherapy is wound healing. With careful planning and precise reconstructive techniques, the use of brachytherapy as a part of salvage or primary surgery does not lead to increased wound morbidity. Reconstructive procedures and a multidisciplinary approach have allowed the delivery of brachytherapy in these complicated patients with low morbidity.

Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.

Free pedicled transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction is often advocated as the procedure of choice for autogenous tissue breast reconstruction in high-risk patients, such as smokers. However, whether use of the free TRAM flap is a desirable option for breast reconstruction in smokers is still unclear. All patients undergoing breast reconstruction with free TRAM flaps at our institution between February of 1989 and May of 1998 were reviewed. Patients were classified as smokers, former smokers (patients who had stopped smoking at least 4 weeks before surgery), and nonsmokers. Flap and donor-site complications in the three groups were compared. Information on demographic characteristics, body mass index, and comorbid medical conditions was used to perform multivariate statistical analysis. A total of 936 breast reconstructions with free TRAM flaps were performed in 718 patients (80.9 percent immediate; 23.3 percent bilateral). There were 478 nonsmokers, 150 former smokers, and 90 smokers. Flap complications occurred in 222 (23.7 percent) of 936 flaps. Smokers had a higher incidence of mastectomy flap necrosis than nonsmokers (18.9 percent versus 9.0 percent; p = 0.005). Smokers who underwent immediate reconstruction had a significantly higher incidence of mastectomy skin flap necrosis than did smokers who underwent delayed reconstruction (21.7 percent versus 0 percent; p = 0.039). Donor-site complications occurred in 106 (14.8 percent) of 718 patients. Donor-site complications were more common in smokers than in former smokers (25.6 percent versus 10.0 percent; p = 0.001) or nonsmokers (25.6 percent versus 14.2 percent; p = 0.007). Compared with nonsmokers, smokers had significantly higher rates of abdominal flap necrosis (4.4 percent versus 0.8 percent; p = 0.025) and hernia (6.7 percent versus 2.1 percent; p = 0.016). No significant difference in complication rates was noted between former smokers and nonsmokers. Among smokers, patients with a smoking history of greater than 10 pack-years had a significantly higher overall complication rate compared with patients with a smoking history of 10 or fewer pack-years (55.8 percent versus 23.8 percent; p = 0.049). In summary, free TRAM flap breast reconstruction in smokers was not associated with a significant increase in the rates of vessel thrombosis, flap loss, or fat necrosis compared with rates in nonsmokers. However, smokers were at significantly higher risk for mastectomy skin flap necrosis, abdominal flap necrosis, and hernia compared with nonsmokers. Patients with a smoking history of greater than 10 pack-years were at especially high risk for perioperative complications, suggesting that this should be considered a relative contraindication for free TRAM flap breast reconstruction. Smoking-related complications were significantly reduced when the reconstruction was delayed or when the patient stopped smoking at least 4 weeks before surgery.

Reconstruction of large sacral defects following total sacrectomy.

Total sacrectomies for cancer ablation often result in extensive defects that are challenging to reconstruct. In an effort to elucidate the criteria to select the most effective reconstructive options, we reviewed our experience with the management of large sacral wound defects. All patients who had a sacral defect reconstruction after a total sacrectomy at our institution between January of 1993 and August of 1998 were reviewed. The size of the defect, the type of reconstruction, postoperative complications, and functional outcome in each patient were assessed. A total of 27 flaps were performed in 25 patients for sacral defect reconstruction after a total sacrectomy. Diagnoses consisted of chordoma (n = 13), giant cell carcinoma (n = 2), sarcoma (n = 5), rectal adenocarcinoma (n = 4), and radiation induced necrosis (n = 1). The size of sacral defects ranged from 18 to 450 cm2 (mean, 189.8 cm2). Ten patients, including five who had preoperative radiation therapy, underwent transpelvic vertical rectus abdominis myocutaneous (VRAM) flap reconstruction for sacral defects with a mean size of 203.3 cm2. Of these, five patients (50 percent) had complications (four minor wound dehiscences and one seroma). Eight patients, including one who had preoperative radiation therapy, underwent bilateral gluteal advancement flap reconstruction for sacral defects with a mean size of 198.0 cm2. They had no complications. Two patients, both of whom had preoperative radiation therapy, underwent gluteal rotation flap reconstruction for sacral defects of 120 cm2 and 144 cm2. Both patients had complications (one partial flap loss and one nonhealing wound requiring a free flap). Three patients, including one who had preoperative radiation therapy, underwent reconstruction with combined gluteal and posterior thigh flaps for sacral defects with a mean size of 246 cm2; two of these patients had partial necrosis of the posterior thigh flaps. Three patients, all of whom had preoperative radiation therapy, underwent free flap reconstruction for sacral defects with a mean size of 144.3 cm2. They had no complications. Our experience suggests that there are three reliable options for the reconstruction of large sacral wound defects: bilateral gluteal advancement flaps, transpelvic rectus myocutaneous flaps, and free flaps. In patients with no preoperative radiation therapy and intact gluteal vessels, the use of bilateral gluteal advancement flaps should be considered. In patients with a history of radiation to the sacral area and in patients whose gluteal vessels have been damaged, the use of the transpelvic VRAM flap should be considered. If the transpelvic VRAM flap cannot be used because of previous abdominal surgery, a free flap should be considered as a last option.

Effect of obesity on flap and donor-site complications in free transverse rectus abdominis myocutaneous flap breast reconstruction.

The purpose of this study was to assess the effect of obesity on flap and donor-site complications in patients undergoing free transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction. All patients undergoing breast reconstruction with free TRAM flaps at our institution from February 1, 1989, through May 31, 1998, were reviewed. Patients were divided into three groups based on their body mass index: normal (body mass index <25), overweight (body mass index 25 to 29), obese (body mass index > or =30). Flap and donor-site complications in the three groups were compared. A total of 936 breast reconstructions with free TRAM flaps were performed in 718 patients. There were 442 (61.6 percent) normal-weight, 212 (29.5 percent) overweight, and 64 (8.9 percent) obese patients. Flap complications occurred in 222 of 936 flaps (23.7 percent). Compared with normal-weight patients, obese patients had a significantly higher rate of overall flap complications (39.1 versus 20.4 percent; p = 0.001), total flap loss (3.2 versus 0 percent; p = 0.001), flap seroma (10.9 versus 3.2 percent; p = 0.004), and mastectomy flap necrosis (21.9 versus 6.6 percent; p = 0.001). Similarly, overweight patients had a significantly higher rate of overall flap complications (27.8 versus 20.4 percent; p = 0.033), total flap loss (1.9 versus 0 percent p = 0.004), flap hematoma (0 versus 3.2 percent; p = 0.007), and mastectomy flap necrosis (15.1 versus 6.6 percent; p = 0.001) compared with normal-weight patients. Donor-site complications occurred in 106 of 718 patients (14.8 percent). Compared with normal-weight patients, obese patients had a significantly higher rate of overall donor-site complications (23.4 versus 11.1 percent; p = 0.005), infection (4.7 versus 0.5 percent; p = 0.016), seroma (9.4 versus 0.9 percent; p <0.001), and hernia (6.3 versus 1.6 percent; p = 0.039). Similarly, overweight patients had a significantly higher rate of overall donor-site complications (19.8 versus 11.1 percent; p = 0.003), infection (2.4 versus 0.5 percent; p = 0.039), bulge (5.2 versus 1.8 percent; p = 0.016), and hernia (4.3 versus 1.6 percent; p = 0.039) compared with normal-weight patients. There were no significant differences in age distribution, smoking history, or comorbid conditions among the three groups of patients. Obese patients, however, had a significantly higher incidence of preoperative radiotherapy and preoperative chemotherapy than did patients in the other two groups. A total of 23.4 percent of obese patients had preoperative radiation therapy compared with 12.3 percent of overweight patients and 12.4 percent of normal-weight patients; 34.4 percent of obese patients had preoperative chemotherapy compared with 24.5 percent of overweight patients and 17.7 percent of normal-weight patients. Multiple logistic regression analysis was used to determine the risk factors for flap and donor-site complications while simultaneously controlling for potential confounding factors, including the incidence of preoperative chemotherapy and radiotherapy. In summary, obese and overweight patients undergoing breast reconstruction with free TRAM flaps had significantly higher total flap loss, flap hematoma, flap seroma, mastectomy skin flap necrosis, donor-site infection, donor-site seroma, and hernia compared with normal-weight patients. There were no significant differences in the rate of partial flap loss, vessel thrombosis, fat necrosis, abdominal flap necrosis, or umbilical necrosis between any of the groups. The majority of overweight and even obese patients who undertake breast reconstruction with free TRAM flaps complete the reconstruction successfully. Both such patients and surgeons, however, must clearly understand that the risk of failure and complications is higher than in normal-weight patients. Patients who are morbidly obese are at very high risk of failure and complications and should avoid any type of TRAM flap breast reconstruction.

Reconstructive approaches in soft tissue sarcoma.

Plastic surgical techniques continue to evolve to deal with problem wounds following soft tissue sarcoma resection. Important advances in how tissue is transferred have allowed most wounds to be closed following extirpation; the emphasis is now placed on refining these transfers while minimizing donor site injury. Reconstructive microsurgery has emerged as a frequently preferred way to resurface wounds after sarcoma resection, particularly in patients who have received radiotherapy or previous surgery. Free flaps provide well-vascularized tissue to fill dead space, cover exposed vital structures, and provide structural support and contour. These procedures demonstrate a high success rate of over 90% and often can ensure a healed wound in a single-stage operation. Creative use of the versatile rectus abdominis or latissimus dorsi myocutaneous flaps can reconstruct the majority of breast, extremity, and head and neck soft tissue defects. Endoscopic harvest of muscle flaps has minimized donor morbidity and scarring. The use of "fillet flaps" is an important concept that spares a patient donor site. Composite free flaps, including bone, are routinely used to rebuild the mandible or other bony structures. The future holds great promise for sarcoma reconstruction because tissue engineering is rapidly closing in on techniques that can duplicate tissues in the laboratory for ultimate use in reconstruction, thus sparing the donor site from disease.

Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery.

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.

How to use a gel template for an exact facial flap transfer.

A variety of materials have been used as template materials to aid in the design of local facial flaps. The biggest criticism of these materials is that they do not conform sufficiently to complex defects. This report describes the use of a hydrogel sheet wound dressing (ClearSite, NDM, Akron, Ohio) as a template material. ClearSite appears to make an ideal template material because it is thin, pliable, transparent, and inexpensive. This gel template adequately conforms to irregular three-dimensional shapes. It has the added beneficial ability to "lift" marking pen lines, which can then be transferred as an exact replica of the defect size. A case is presented in which a ClearSite template directed the transfer of the exact amount of forehead tissue following excision of a complex congenital nevus of the nose. Use of the ClearSite template seems well suited to help in local facial flaps and is likely to simplify the design of many distant flaps as well.

A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas.

BACKGROUND: Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas. METHODS: Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 micrograms subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded. RESULTS: Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different. CONCLUSIONS: Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas.

Evidence for IFN-gamma as a mediator of the lethality of endotoxin and tumor necrosis factor-alpha.

Current evidence indicates that endogenously produced peptide cytokines, most notably TNF-alpha and IL-1, mediate the lethality of experimental endotoxemia. Because circulating serum levels of IFN-gamma can be detected soon after TNF-alpha and IL-1 in response to endotoxin, we investigated the role of IFN-gamma in endotoxin and TNF-alpha lethality. Specific neutralizing antibodies to murine TNF-alpha (anti-TNF-alpha Ab) or murine IFN gamma (anti-IFN-gamma Ab) produced in our laboratory protected mice against the lethality of Escherichia coli endotoxin (LPS) administered 6 h later. Serum IFN-gamma levels 2 h after i.v. LPS were lower in mice treated with anti-TNF-alpha Ab compared to mice that received nonimmune IgG (median less than 2.5 vs 3.0 U/ml, P2 less than 0.05). In contrast, serum TNF-alpha levels 1 h after i.v. LPS peaked more than fourfold higher in mice treated with anti-IFN-gamma Ab compared to controls (median greater than 6400 vs 1405 pg/ml, p2 less than 0.05). Doses of TNF-alpha (300 micrograms/kg) and IFN-gamma (50,000 U) which were well tolerated when given individually were synergistically lethal in combination (0% lethality vs 100% lethality, P2 less than 0.001), and were associated with higher serum levels of IL-6 than with either cytokine alone. Anti-IFN-gamma Ab provided complete protection against exogenous human rTNF-alpha at the LD100 dose (1400 micrograms/kg, p2 less than 0.001), and in fact prevented lethality at doses four- to fivefold greater than the LD100 human rTNF-alpha (up to 6000 micrograms/kg). We conclude that IFN-gamma is synergistic with TNF-alpha, is essential for the lethality of LPS and TNF-alpha, and may have modulating effects on the negative control of serum levels of TNF-alpha after LPS in mice.

Role of tumor necrosis factor in oxygen toxicity.

mRNA from lungs of mice exposed to high-dose oxygen (greater than 95%) for 3 days demonstrated increased expression of the genes for tumor necrosis factor (TNF), interleukin-1, and interleukin-6 compared with mRNA from lungs of mice exposed to room air. Daily treatment of mice exposed to high-dose oxygen with an antibody to TNF improved survival compared with mice receiving a similar dose of control immunoglobulin G. Pretreatment of mice with repetitive sublethal intraperitoneal doses of recombinant human TNF for 3 days or a single intravenous dose followed by exposure to high-dose oxygen afforded a significant survival advantage compared with high-dose oxygen-exposed mice pretreated with vehicle or interleukin-1. The repetitive intraperitoneal TNF pretreatment reduced the development of interstitial pneumonitis, pulmonary edema, and lung weight gain associated with oxygen toxicity and enhanced expression of the gene for the free radical protective enzyme manganous superoxide dismutase in lung tissue, a gene that is augmented as mice are exposed to high-dose oxygen. Furthermore a single intravenous dose of TNF 24 h after oxygen exposure was still protective. The results suggest that the toxicity of oxygen therapy can be partially ameliorated by either treatment with anti-TNF antibody or pretreatment and early treatment with TNF. These findings are consistent with the hypothesis that oxygen exposure induces TNF, which causes part of the toxicity of high-dose oxygen, and that pretreatment or early treatment with TNF induces the gene for an enzyme that recently has been shown to be very effective in protecting mice from the toxicity of oxygen.