Bile duct apoptosis and cholestasis resembling acute graft-versus-host disease after autologous hematopoietic cell transplantation.

BACKGROUND: Acute graft-versus-host disease (GVHD) of the liver is a frequent complication of allogeneic hematopoietic cell transplantation. This report describes hepatic GVHD following autologous transplantation. METHODS: We reviewed 116 consecutive autologous transplant recipients. A diagnosis of GVHD was based on histology (segmental to subtotal destruction of bile ductal epithelial cells with apoptosis and lymphocytic infiltrates), clinical criteria (elevated serum alkaline phosphatase), a response to immunosuppressive therapy, and finding no other cause for cholestatic liver disease. RESULTS: Two patients developed cholestatic liver disease (alkaline phosphatase levels over five times the normal upper limit) and had liver biopsies showing apoptotic and dysmorphic ductular epithelial cells typical of GVHD. Three additional patients developed cholestasis and intestinal symptoms but had gastric biopsies only, showing apoptotic crypt epithelial cells and crypt cell drop-out typical of GVHD. CONCLUSION: Two recipients of autologous hematopoietic cells developed histologic abnormalities of small bile ducts and cholestatic liver disease resembling GVHD of the liver after allogeneic transplant. The mechanisms of bile duct damage in this setting may involve immune dysregulation related to reconstitution of immunity with peripheral blood stem cells.

Biliary obstruction in hematopoietic cell transplant recipients: an uncommon diagnosis with specific causes.

Jaundice is a common problem in marrow transplant recipients. The incidence of bile duct obstruction in this setting is unknown. The purpose of this study was to determine the incidence of biliary obstruction, the causes, and outcomes following marrow transplant. Consecutive cases were reviewed at two major transplant centers in the United States from 1969 to 1996 at the Fred Hutchinson Cancer Research Center and 1989 to 1996 at the City of Hope National Medical Center. Nine cases of biliary obstruction were identified as a cause of jaundice in 7412 marrow transplant recipients, an incidence of 0.12%. The presentation was bimodal, with seven cases occurring prior to day 100 and two occurring 2 to 4 years after transplantation. The age distribution was 15 to 50 years and all patients had received allogeneic transplants. The causes of obstruction included gallbladder sludge (n=1), a duodenal hematoma (n=1), choledocholithiasis with biliary pancreatitis (n=1), bile duct infection (n=2), recurrent malignancy (n=1), choledocholithiasis associated with a benign stricture (n=1), Epstein-Barr virus-related lymphoproliferative disorder (n=1), and a benign stricture of unknown etiology (n=1). Biliary obstruction is a rare cause of jaundice in the post-transplant period. The presentation was similar to that of other post-transplant hepatobiliary problems, but with disparate causes.

The extended Abbé flap.

Large upper lip defects that include the surrounding aesthetic subunits of the midface are difficult to reconstruct. Abbé flaps have been a popular method of dealing with small upper lip defects but, as classically described, they are insufficient for larger defects. We performed cadaver injections to evaluate the vascular territory supplied by the inferior labial artery with particular attention to the submental area. Extended Abbé flaps were then designed and used in combined upper lip and midfacial reconstruction. Three cases and guidelines for the use of the extended Abbé flap are presented.

Mandibular reconstruction with transforming growth factor-beta1.

HYPOTHESIS: Transforming growth factor-beta1 (TGF-beta1) plus demineralized bone matrix (DBM) will reconstruct a critical mandibular defect devoid of periosteum in a canine model. STUDY DESIGN: Randomized, blinded, placebo-controlled, prospective animal pilot study. METHODS: Canine critical mandibular defects devoid of periosteum were reconstructed with DBM (group 1, n = 3) and DBM plus TGF-beta1 (250 microg TGF-beta1/g DBM) (group 2, n = 3). Radiologic, histologic, and biomechanical testing was performed on the test group and control group specimens at 12 weeks after implantation. RESULTS: A palpable bone bridge was present in the group 2 subjects 5 to 6 weeks after implantation and was never present in the group 1 subjects. Radiologic and histologic examination at the time of harvest (12 weeks after implantation) demonstrated a solid bone bridge in the group 2 subjects and a fibrous union in the group 1 subjects. Group 2 specimens demonstrated failure in four-point bending testing at an average maximum moment of 9.9 +/- 2.2 N-m. This value was 9.4% of the maximum moment of the contralateral nonoperated side. Group 1 specimens were palpably flexible on plate removal and had a biomechanical strength of 0. The difference in strength between group 1 and group 2 was statistically significant (P < 0.02), supporting the hypothesis that the addition of TGF-beta1 to the DBM carrier resulted in the formation of significantly stronger bone in the critical gap. CONCLUSION: The addition of TGF-beta1 to DBM results in healing of a critical bone defect devoid of periosteum in a higher mammalian model.

Nasal reconstruction with articulated irradiated rib cartilage.

Nasal structural reconstruction is a formidable task in cases where there is loss of support to both the nasal dorsum and tip. A multitude of surgical approaches and materials have been used for the correction of the saddle-nose deformity with varying degrees of success. Articulated irradiated rib cartilage inserted through an external rhinoplasty approach was used to reconstruct nasal deformities in 18 patients over a 6-year period. Simultaneous use of a midline forehead flap to reconstruct the overlying soft tissue was required in four cases. Follow-up ranged from 1 to 6 years (mean, 2.8 years). Results were rewarding in most cases with marked improvement in nasal support and airway. Revision and/or replacement secondary to trauma or warping of the graft was required in four cases. None of the patients exhibited infection, extrusion, or noticeable resorption. A description of the surgical technique, review of all the cases, and recommendation for continued use of this graft material are discussed.

Suspended circummandibular wire fixation for mixed-dentition pediatric mandible fractures.

OBJECTIVE: To introduce and evaluate the technique of cirummandibular wires with piriform rim suspension (CMW-PRS) combined with arch bars and a fracture site bridle in the treatment of mixed-dentition pediatric mandible fractures. DESIGN: Five male patients (mean age, 8.2 years [age range, 7-10 years]) with an isolated mixed-dentition mandible fracture were treated with the CMW-PRS technique at the University of Texas Health Science Center, San Antonio, from 1985 to 1987 and at the University of Missouri, Columbia, from 1992 to 1995. Clinical and radiographic fracture healing, somatosensory status, and complications were evaluated. RESULTS: All patients demonstrated clinical union to their preinjury occlusion by 3 or 4 weeks. They remained without complications until they were no longer available for follow-up. Panoramic radiographs supported the findings of clinical examinations throughout the study, and no radiographic abnormalities were found. There were no somatosensory disturbances of the lingual or mental/inferior alveolar nerves. One patient required a tracheostomy unrelated to the procedure. CONCLUSION: The CMW-PRS technique combined with arch bars and a fracture site bridle wire achieved equivalent historical results when compared with the dental splint. The potential advantages and disadvantages of the CMW-PRS technique compared with those of monocortical bone plating, as well as the significant advantages of the CMW-PRS over the dental splint, are discussed in the text.

Cervical rotation flaps for midface resurfacing.

The midface has long served as a focus for creativity in surgical reconstruction. Full-thickness skin grafts, split-thickness grafts, and distal flaps have long been used to attempt to reduplicate existing anatomy in this area. Recent reconstruction efforts have focused on the creative use of microvascular free flaps for this purpose. This article reports on the use of extensively developed regional rotation flaps as an excellent reconstructive modality for use in this area of the face. The details of surgical incisional planning are given. The nuances of surgical creation of these flaps and their rotation and suspension into place are given. The cases we have done using this technique for the past 3 years are reviewed. Our present indications for use of these flaps and their limitations are given.

Necrotizing fasciitis of the eyelids.

Necrotizing fasciitis is a destructive soft tissue infection that rarely involves the eyelids. Three cases of necrotizing fasciitis of the eyelids are described. Necrotizing fasciitis was preceded by minor forehead soft tissue trauma in two cases and occurred spontaneously in one. In two patients necrotizing fasciitis was bilateral and involved both the upper and lower eyelids. Review of these cases, in addition to 18 cases previously reported in the English literature, reveals a predominance in females, preceding minor local soft tissue trauma, frequent bilateral involvement, and an association with alcohol abuse and diabetes. In all of the patients, group A beta-hemolytic streptococci were cultured from the wound. Early recognition of the disease process, prompt surgical debridement of the necrotic tissue, aggressive antimicrobial therapy, and delayed skin grafting combine to minimize morbidity.

Nasal reconstruction using the inferior turbinate mucosal flap.

Reconstruction of nasal defects can be a difficult task if large amounts of nasal mucosa are missing. We have found the inferior turbinate mucosal flap to be a reliable and effective flap in a series of 16 patients undergoing nasal reconstruction or repair of septal perforations. Most of these patients had insufficient mucosa to use traditional flaps harvested from the nasal floor or the lateral nasal wall. Eight patients underwent reconstruction of septal perforations, 9 patients underwent nasal reconstruction of large nasal defects after tumor extirpation, and 1 patient underwent closure of a palatal fistula. Six of the septal perforations were closed completely and 3 were reduced in size by 50%. All 11 turbinate flaps used for nasal reconstruction (2 patients had bilateral flaps) survived. Two flaps underwent mild superficial epidermolysis without flap necrosis or exposure of overlying cartilage grafts. The turbinate flap is based anteriorly and provides large amounts of well-vascularized mucosa. The turbinate is rotated anteriorly and bivalved and the conchal bone is removed to increase the dimensions of the flap. The flap is sometimes staged to allow transfer of mucosa to distant sites, such as the septum, the nasal ala, and the nasal wall. An anatomical dissection of 10 turbinate flaps on 5 fresh cadaver specimens demonstrated an average flap size of 4.97 cm2. The average length of the flap was 2.83 cm, which is sufficient length to reach the nasal dorsum. A description of the surgical technique and the vascular supply of this flap will be discussed.

Measuring cosmetic facial plastic surgery outcomes: a pilot study.

OBJECTIVE: To test 4 previously published outcomes instruments (the Facelift Outcomes Evaluation, the Rhinoplasty Outcomes Evaluation, the Blepharoplasty Outcomes Evaluation, and the Skin Rejuvenation Outcomes Evaluation) in terms of their reliability and validity in assessing patient-related outcomes of surgical intervention. DESIGN: A prospective pilot study of 78 patients in 3 similar private cosmetic surgery centers undergoing a total of 100 face-lift, rhinoplasty, blepharoplasty, and skin rejuvenation procedures. Patients were evaluated at 2 preoperative and 1 postoperative time points and the instruments were analyzed with regard to their test-retest reliability, internal consistency, and responsiveness to change. RESULTS: All 4 outcomes instruments had excellent reliability, consistency, and validity scores. Test-retest reliability was 0.74 to 0.83 (Pearson correlation coefficients), internal consistency scores were.83 to.88 (Cronbach alpha), and responsiveness to change was statistically significant for each instrument tested (P< or =.001). In addition, patients experienced significant quality of life improvement, with overall satisfaction increasing on average from 37% to more than 84% after these procedures. CONCLUSIONS: These 4 instruments are reliable and valid and can be used to accurately assess patient-related satisfaction in studies of face-lift, rhinoplasty, blepharoplasty, and skin resurfacing outcomes. These brief questionnaires provide the cosmetic surgeon with quantitative tools to evaluate otherwise subjective and purely qualitative outcomes and are recommended for use in future prospective studies.

Microvascular free flap reconstructive options in patients with partial and total maxillectomy defects.

OBJECTIVE: To evaluate and discuss the free flap reconstructive options for patients with partial and total maxillectomy defects. DESIGN: Retrospective review of cases. SETTING: Two tertiary referral centers. PATIENTS: Fifty-one patients had partial or total maxillectomy defects resulting from oncologic surgical resection, and 7 had partial maxillectomy defects resulting from trauma. Inferior or partial maxillectomy defects included 10 anterior arch and hemipalate defects and 12 subtotal or total palate defects. Total maxillectomy defects with and without orbital exenteration included 36 maxilla defects with hemipalate and malar eminence. INTERVENTION: There were 11 fibula, 14 rectus abdominis, 9 scapular, 10 radial forearm, 5 latissimus dorsi, and 13 combination latissimus dorsi and scapular flaps. MAIN OUTCOME MEASURES: Separation of the oral cavity from the sinonasal cavities, diet, type of dental restoration, type of orbital restoration, speech intelligibility, and complications. RESULTS: Only 1 flap failure was reported. There was loss of bone in 2 flaps and loss of the skin paddle in 1 flap. All palatal defects were sealed by the separation of the oral and sinonasal cavities. Thirty-eight patients were able to eat a regular diet while the remaining patients maintained a soft diet. All patients conversed on the telephone without difficulty in intelligibility. Eight patients had an implant-borne dental prosthetic, and 30 patients had a conventional partial prosthetic. Orbit restoration was achieved in 2 patients with an implant-borne prosthetic, and 6 patients retained a standard orbit prosthetic. CONCLUSIONS: Free flap reconstruction of the maxilla creates reproducible permanent separation of the oral and sinonasal cavities in a single-stage procedure. In addition, there exists the potential for dental rehabilitation with restoration of masticatory and phonatory function. Free flap reconstruction also provides a good cosmetic result, which improves patients' outlook and contributes to their overall well-being. Reconstructive flaps are designed to fit specific maxillary defects and patient needs to provide optimally functional and cosmetic results.

Skin anatomy and flap physiology.

This article focuses on three main areas, which includes an overview of skin anatomy, different types of skin flaps and their vascular supply, and several aspects of flap biomechanics to allow the surgeon to perform the most adequate reconstruction with regard to location and size of defects.

Cheek repair.

The cheek, one of the most important facial aesthetic units, adjoins key facial structures including the mouth, nose, and eyelids. When undertaking cutaneous cheek defect repair, these functional structures must remain undisturbed. Indeed, the size, depth, and position of each defect must be critically assessed in relation to surrounding donor tissue and landmarks. This article reviews cheek anatomy, surface landmarks, and the various surgical options for achieving successful aesthetic and functional repair.

Management of scar contractures, hypertrophic scars, and keloids.

Aberrant fibrous tissue formation after surgery or trauma still presents a challenge to surgeons. Current research hopes to identify the characteristics of the population of fibroblasts that lead to hypertrophic or keloid scar formation. Surgical procedures and laser therapy followed by intralesional steroid treatments still are the foundation of treatment; but new modalities are being applied. The pathogenesis and management of hypertrophic scars, keloids, and scar contractures are discussed in this article.

Tissue expansion and serial excision in scar revision.

Scars in the head and neck caused by trauma or extirpative surgery can present a significant problem to the patient and may require revision. A variety of techniques, both surgical and nonsurgical, exists for treatment of unsightly scars. Surgical excision of scars relies upon recruitment of local tissue for closure of the ensuing defect. Tissue expansion and serial scar excision may be used to provide more tissue for advancement or local flap coverage of revised scars. Herein we review the history, technique, and complications of tissue expansion and serial excision as well as the basic scientific principles underlying these techniques.

Buffered local anesthetics and epinephrine degradation.

Lidocaine with epinephrine is currently the most common local anesthetic agent used for facial soft tissue surgery. This combination is generally safe and effective in providing complete anesthesia and adequate hemostasis. Because epinephrine is unstable at physiologic pH, the commercial preparation is formulated with a low pH (3.5-5.5). Unfortunately, this acidic pH causes significant pain during infiltration. To reduce pain, clinicians sometimes buffer acidic local anesthetic agents with sodium bicarbonate. However, little is known about the stability of epinephrine when the pH of epinephrine is clinically altered. Using high pressure liquid chromatography (HPLC), epinephrine levels were measured after the addition of sodium bicarbonate. Our results indicate a significant amount of epinephrine degradation occurs in some of these specimens. Recommendations regarding the use of buffered local anesthetic agents are made.

Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver.

OBJECTIVE: To determine the safety and efficacy of ursodeoxycholic acid treatment in patients with chronic graft-versus-host disease (GVHD) of the liver. DESIGN: Open-label study in which each patient served as his or her own control. SETTING: Private practice and a university bone marrow transplant center. PATIENTS: Twelve patients with refractory chronic GVHD of the liver were studied after allogeneic bone marrow transplantation. INTERVENTIONS: After baseline data collection, patients were given ursodeoxycholic acid (UDCA, 10 to 15 mg/kg body weight per day) for 6 weeks. After discontinuation of the drug, patients were followed for an additional 6 weeks. Doses of immunosuppressive drugs were unchanged for these 12 weeks. MEASUREMENTS: Signs, symptoms, Karnofsky performance scores, hematocrit, total leukocyte count, absolute neutrophil count, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyltransferase (GGT), total serum bilirubin, prothrombin time, serum creatinine, and blood urea nitrogen were assessed. RESULTS: Serum tests of cholestatic liver injury measured at 2, 4, and 6 weeks showed improvement compared with baseline. At 6 weeks, the percent decrease from baseline in total serum bilirubin was 33% (P less than 0.005); in alkaline phosphatase the decrease was 32% (P less than 0.038); and in AST the decrease was 37% (P less than 0.007). After discontinuation of UDCA therapy, 11 patients were followed for 6 additional weeks. All showed significant worsening in liver function test results. Symptom scores were unchanged throughout the study. One patient with pruritus improved while receiving therapy with UDCA. No adverse effects were observed. CONCLUSION: Therapy with UDCA was safe, well-tolerated, and efficacious in the short-term treatment of refractory chronic GVHD of the liver. Further investigation is needed to evaluate the long-term effects of UDCA therapy.

Cirrhosis of the liver in long-term marrow transplant survivors.

Patients who survive hematopoietic cell transplantation (HCT) have multiple risk factors for chronic liver disease, including hepatitis virus infection, iron overload, and chronic graft-versus-host disease (GVHD). We studied 3,721 patients who had survived 1 or more years after HCT at a single center and identified patients with histologic or clinical evidence of cirrhosis. Risk factors for the development of cirrhosis were evaluated and compared with a group of matched control subjects. Cirrhosis was identified in 31 of 3,721 patients surviving 1 or more years after HCT, 23 of 1,850 patients surviving 5 or more years, and in 19 of 860 patients surviving 10 or more years. Cumulative incidence after 10 years was estimated to be 0.6% and after 20 years was 3.8%. The median time from HCT to the diagnosis of cirrhosis was 10.1 years (range, 1.2 to 24.9 years). Twenty-three patients presented with complications of portal hypertension, and 1 presented with hepatocellular carcinoma. Thirteen patients have died from complications of liver disease, and 2 died of other causes. Three patients have undergone orthotopic liver transplantation. Hepatitis C virus infection was present in 25 of 31 (81%) of patients with cirrhosis and in 14 of 31 (45%) of controls (P =.01). Cirrhosis was attibutable to hepatitis C infection in 15 of 16 patients presenting more than 10 years after HCT. There was no difference in the prevalence of acute or chronic GVHD, duration of posttransplant immunosuppression, or posttransplant marrow iron stores between cases and controls. Cirrhosis is an important late complication of hematopoietic cell transplantation and in most cases is due to chronic hepatitis C. Long-term survivors should be evaluated for the presence of abnormal liver function and hepatitis virus infection.

Severe gastrointestinal bleeding after hematopoietic cell transplantation, 1987-1997: incidence, causes, and outcome.

OBJECTIVE: Severe GI bleeding after hematopoietic cell transplantation is commonly due to lesions that are unusual in nontransplant patients. The frequency of GI bleeding appears to have decreased over the last decade, but the reasons have not been readily apparent. We sought to determine the incidence of severe bleeding during two time periods, to describe the causes and outcomes of bleeding, and to analyze the reasons behind an apparent decline in severe bleeding over the decade covered. METHODS: During 1986-1987 and 1996-1997, we followed all patients with and without severe bleeding at our institution, a marrow transplant center. RESULTS: Over this decade, the incidence of severe bleeding declined from 50/467 (10.7%) to 15/635 (2.4%) (p < 0.0001). Overall mortality from intestinal bleeding declined from 3.6% to 0.9% (p = 0.002), but mortality in those with bleeding remained high (34% vs 40%). The onset (day 42 vs 47) and platelet counts (35,994 vs 37,600/microl) were similar, but the sites and causes of bleeding were different. During 1986-1987, 27/50 patients bled from multiple GI sites, viral and fungal ulcers, or graft-versus-host disease (GVHD). Over the decade, bleeding from GVHD had decreased 80% (p < 0.0001), and bleeding from viral (p < 0.0001) and fungal (p = 0.023) ulcers almost disappeared. CONCLUSIONS: The incidence of severe GI bleeding has declined significantly over the last decade because of prevention of viral and fungal infections and severe acute GVHD. However, severe bleeding after transplant remains a highly morbid event, particularly among patients with GVHD.