Fibrous Obliteration Research Articles

Giant Multilocular Prostatic Cystadenoma Presenting with Obstructive Aspermia

Giant multilocular prostatic cystadenoma (GMPC) is a rare benign tumor involving the prostate gland. Microscopically, it masquerades phyllodes tumor or transitional zone hyperplasia. We report one case of GMPC arising from the prostate central zone (CZ), presenting with long-standing aspermia associated with seminal vesicle fibrous obliteration.

Effects of Blockade of the Renin–Angiotensin and Endothelin Systems on Experimental Bronchiolitis Obliterans

Blockade of the renin-angiotensin and the endothelin (ET) systems ameliorates fibrous airway obliteration in rat tracheal allografts. The aim of this study was to test which of these pharmacologic interventions attenuates the process more effectively, and whether combination therapy confers additional benefit. Rat tracheas were heterotopically transplanted from Brown-Norway donors into Lewis recipients. Recipients received the dual endothelin-1 (ET-1) receptor blocker, bosentan (100 mg/kg), the angiotensin-converting enzyme (ACE) inhibitor, ramipril (5 mg/kg), bosentan plus ramipril (doses as just noted) or vehicle. Grafts were harvested at Days 7 and 21 for morphometric studies and molecular analysis by real-time polymerase chain reaction (PCR). At Day 21, bosentan and ramipril treatment reduced the percentage of luminal occlusion compared with vehicle to a similar extent. In animals that received the combined treatment, luminal obliteration was further reduced compared with the respective monotherapies. Furthermore, rats treated with bosentan plus ramipril showed a lower percent of epithelial necrosis. The beneficial effects of bosentan and ramipril, alone or in combination, were associated with reduced mRNA levels of transforming growth factor (TGF)-beta1 and platelet-derived growth factor (PDGF)-A in the tracheal allografts. Our data suggest that ET receptor blockade prevents fibrous airway obliteration to a similar extent as ACE inhibition in this model. Interruption of both pathways provides superior graft protection as compared with single-system blockade.

Laparoscopic Obliteration of the Nephrosplenic Space Using Polypropylene Mesh in Five Horses

To report a laparoscopic technique for insertion of polypropylene mesh in the nephrosplenic space in horses and evaluate outcome. Descriptive experimental study. Five healthy mature horses. One laparoscope and 2 instrument portals were made on the left side of the horse. The nephrosplenic space was measured and appropriately sized polypropylene mesh was inserted and attached to the dorsolateral splenic capsule and perirenal fascia using helical titanium coils. All horses had repeat laparoscopy 4 weeks later and were necropsied at intervals 4-14 weeks after mesh placement. Mean time for laparoscopic mesh placement was 104 minutes. None of the horses had signs of colic and at 4 weeks all mesh implants were covered by fibrous tissue. One horse had a descending colon mesenteric adhesion to the mesh. At necropsy, the fibrous tissue covering the mesh had adhered to itself and pulled the splenic capsule and perirenal fascia into close apposition. Each mesh implant was firmly adhered to the spleen, nephrosplenic ligament, and perirenal fascia. Laparoscopic mesh placement was easily performed, well tolerated, and provided excellent fibrous obliteration of the nephrosplenic space. The single important complication observed was a mesenteric adhesion of the descending colon to the mesh in 1 horse. Laparoscopic placement of polypropylene mesh leads to obliteration of the nephrosplenic space within 4 weeks and should prevent entrapment of viscera in the nephrosplenic space.

Obligatory Role for Interleukin-13 in Obstructive Lesion Development in Airway Allografts

The pathogenesis of bronchiolitis obliterans (BO), a common and devastating obliterative disorder of small airways following lung transplantation, remains poorly understood. Lesions are characterized in their early stages by lymphocyte influx that evolves into dense fibrotic infiltrates. Airway specimens taken from patients with histological BO revealed infiltrating myofibroblasts, which strongly expressed the signaling chain of the high affinity interleukin-13 (IL-13) receptor IL-13Ralpha1. Because IL-13 has proinflammatory and profibrotic actions, a contributory role for IL-13 in BO development was examined using murine models of orthotopic and heterotopic tracheal transplantation. Compared with airway isografts, allografts exhibited a significant increase in relative IL-13 mRNA and protein levels. Allogeneic tracheas transplanted into IL-13-deficient mice were protected from BO in both transplant models. Flow cytometric analysis of orthotopic transplant tissue digests revealed markedly fewer infiltrating mononuclear phagocytes and CD3(+) T lymphocytes in IL-13-deficient recipients. Furthermore, protection from luminal obliteration, collagen deposition, and myofibroblast infiltration was observed in heterotopic airways transplanted into the IL-13(-/-) recipients. Transforming growth factor-beta1 expression was significantly decreased in tracheal allografts into IL-13(-/-) recipients, compared to wild-type counterparts. These human and murine data implicate IL-13 as a critical effector cytokine driving cellular recruitment and subsequent fibrosis in clinical and ex-perimental BO.

Characterization of acrylic polyamide plastic embolization particles in vitro and in human tissue sections by light microscopy, infrared microspectroscopy and scanning electron microscopy with energy dispersive X-ray analysis

Vascular embolization is a well-established practice for the treatment of tumors and vascular lesions. Rounded beads (microspheres) of various materials (collagen, dextran and trisacryl-polymer-gelatin) were developed to solve problems encountered with earlier versions of embolic material. We performed histochemistry, Fourier transform infrared microspectroscopy and scanning electron microscopy with energy dispersive X-ray analysis on two uterine and one hepatic specimen with unidentified intravascular foreign material, and examined a reference embolization product for comparison. The hematoxylin and eosin stained tissue sections showed multiple foci with unidentified intravascular foreign material and fibrous obliteration of vessel lumens. Only one case had a clinical history of previous embolization but without specifying the material used. One case was submitted for identification of a ‘parasite'. The material stained positively with Sirius red and mucicarmine, variably with Masson's trichrome stain and Movat pentachrome, and did not stain centrally with periodic acid Schiff with diastase. Infrared spectrophotometric analysis of the material from all three cases demonstrated the spectrum of acrylic polyamide plastic. A control sample of EmboGold™ exhibited infrared microspectroscopic spectra similar to the three tissue specimens. Analysis by scanning electron microscopy with energy dispersive X-ray analysis demonstrated some differences in elemental composition between the tissue sections and the selected reference material. To our knowledge, this is the first report of infrared spectrophotometric analysis with scanning electron microscopy with energy dispersive X-ray analysis of an acrylic polyamide plastic embolization product both in vitro and in human histologic tissue sections. In cases lacking appropriate clinical information, identification by these methods and/or a panel of special stains may assist pathologists unfamiliar with this material's light microscopic appearance.

Obliteration der Cochlea beim Cogan-Syndrom - Bedeutung für die Cochlear-Implant-Chirurgie

Acute, often bilateral deafness in Cogan's syndrome or other autoimmune diseases is caused by autoimmune mediated inflammatory attack on the membranous labyrinth. Auditory rehabilitation in case of bilateral deafness can be achieved by cochlear implant surgery. A retrospective analysis of all patients suffering from Cogan's syndrome that had received a cochlear implant, was carried out. 6 of 295 adult patients (2.6 %) that had received a cochlear implant, had become deaf due to Cogan's syndrome. Partial obliteration or ossifikation was encountered in all cases and influenced surgical procedure. In one case a fibrous obliteration of the scala tympani was found 8 weeks after acute onset of complete deafness. The course of obliteration is unknown. With regard to our results a fibrous obliteration may occur as early as 8 weeks after complete deafness. This has to be considered in counseling of patients. Only early cochlear implant surgery facilitates best possible rehabilitation results.

Miscellaneous conditions of the appendix

A variety of miscellaneous conditions affect the appendix, both as incidental findings and as causes of clinical signs and symptoms that often mimic appendicitis. Congenital abnormalities of the appendix are rare; the two most commonly reported are congenital absence and appendiceal duplication. Diverticular disease may be an incidental finding, but when inflamed, can be clinically confused with appendicitis. Endometriosis of the appendix, which usually occurs in the setting of generalized gastrointestinal endometriosis, often presents as acute appendicitis, but may present as intussusception, lower intestinal bleeding, and, particularly during pregnancy, perforation. Peritoneal endosalpingiosis often involves the appendiceal serosa and occasionally the wall but has no clinical manifestations in contrast to endometriosis. Vasculitis may be either isolated to the appendix or part of a systemic vasculitis, most often polyarteritis nodosa. Neural proliferations of the appendix include lesions associated with von Recklinghausen's disease, as well as mucosal and axial neuromas that are theorized to progress to fibrous obliteration of the appendix. Mesenchymal tumors of the appendix are most often of smooth muscle type, usually leiomyoma but rarely leiomyosarcoma; nonmyogenic neoplasms such as gastrointestinal stromal tumor, granular cell tumor, Kaposi's sarcoma, and miscellaneous other curiosities occur rarely. Lymphoma affects the appendix exceptionally; in children, Burkitt lymphoma is most common whereas in adults, large cell lymphomas and low grade B-cell lymphomas predominate. Secondary involvement of the appendix by leukemia has been reported. Secondary involvement of the appendix by carcinomas of the female genital tract, particularly ovary, and diverse other sites are in aggregate common but only rarely a clinical or pathological difficulty. Occasionally, however, appendiceal neoplasia that is secondary from another site may dominate the clinical picture and lead to potential pathologic misdiagnosis as primary appendiceal disease.

Biliary atresia revisited.

Extrahepatic biliary atresia (EHBA) is an inflammatory fibrosing process affecting the extrahepatic and intrahepatic biliary tree resulting in fibrous obliteration of the extrahepatic biliary tract, ductopenia of intrahepatic bile ducts, and biliary cirrhosis. EHBA is divided into a correctable and a noncorrectable type with focal patency of the otherwise atretic biliary tree in the former and no patency of the biliary tree in the noncorrectable type. EHBA is divided in a fetal, prenatal or embryonic, and a more common, perinatal, acquired form. The symptoms of the former start shortly after birth and there is frequently an association with a variety of congenital anomalies. Children with the perinatal form become jaundiced several weeks after birth; no associated congenital anomalies are present. Morphologically, an inflammatory and fibrosing process of the extrahepatic biliary tree leads to complete lumenal obliteration. The liver is characterized by a nonspecific giant cell transformation, and portal expansion by fibrous connective tissue with marked ductular proliferation. With time, ductopenia and biliary cirrhosis develop. The diffential diagnosis with other conditions with similar microscopic patterns such as as alpha-1 antitrypsin deficiency, total parental nutrition, obstruction by a choledochal cyst, arteriohepatic dysplasia, familial progressive intrahepatic cholestasis, and alteration of the bile acid metabolism is discussed. In the fetal group, abnormalities in different genes seem to play a role; ductal plate malformation is another possibility. Different etiologies have been postulated in the perinatal form of EHBA: genetic susceptibility, vascular factors, toxins, and infections mainly by rotavirus and reovirus. The pathogenesis is complex. EHBA is a heterogenous disease, resulting from a combination of genetic factors, insults, and activation of different genetic and immunologic pathways. The treatment of EHBA is surgical, with anastomosis between the biliary tree and the intestine in the correctable type and a hepatic portoenterostomy (HPE) for the noncorrectable group. HPE is a temporizing treatment allowing the infant to develop and grow, followed in the majority of the patients by liver transplantation.

The canals of hering might represent a target of methotrexate hepatic toxicity.

Methotrexate treatment for psoriasis is known to cause hepatic fibrosis in some patients, which might progress to cirrhosis. The fine, radiating, fibrous septa developing in this setting have a distribution that is reminiscent of the location of the canals of Hering (coH). To assess the possibility of fibrous obliteration of the coH in patients receiving methotrexate, we developed a staining technique by combining an immunohistochemical stain for cytokeratin 7 with a modified Masson trichrome. Sixteen biopsy specimens from 7 patients were evaluated. The biopsies had a variety of histologic changes, including steatosis, anisonucleosis, multinucleation, chronic inflammation, bile duct damage, and ductular reaction. Fibrosis was present in 13 biopsy specimens (81%) and was mild in 7, moderate in 3, and severe in 3 specimens. Compared with normal (control) liver specimens, biopsy specimensfrom patients receiving methotrexate had decreased numbers of coH (1.9 +/- 0.8 vs 5.2 +/- 1.7; P < .025). In specimens with moderate or severe fibrosis, fibrous septa sometimes extended along the coH. These findings suggest that scarring of the coH might be a consequence of the toxic effects of methotrexate.

The Canals of Hering Might Represent a Target of Methotrexate Hepatic Toxicity

Methotrexate treatment for psoriasis is known to cause hepatic fibrosis in some patients, which might progress to cirrhosis. The fine, radiating, fibrous septa developing in this setting have a distribution that is reminiscent of the location of the canals of Hering (coH). To assess the possibility of fibrous obliteration of the coH in patients receiving methotrexate, we developed a staining technique by combining an immunohistochemical stain for cytokeratin 7 with a modified Masson trichrome. Sixteen biopsy specimens from 7 patients were evaluated. The biopsies had a variety of histologic changes, including steatosis, anisonucleosis, multinucleation, chronic inflammation, bile duct damage, and ductular reaction. Fibrosis was present in 13 biopsy specimens (81%) and was mild in 7, moderate in 3, and severe in 3 specimens. Compared with normal (control) liver specimens, biopsy specimens from patients receiving methotrexate had decreased numbers of coH (1.9 ± 0.8 vs 5.2 ± 1.7; P < .025). In specimens with moderate or severe fibrosis, fibrous septa sometimes extended along the coH. These findings suggest that scarring of the coH might be a consequence of the toxic effects of methotrexate.

Treatment options of unruptured intracranial aneurysms.

Aneurysmal subarachnoid hemorrhage (SAH), despite improvements in surgical and medical treatment, is still a serious disease with high rates of case fatality (40% to 50%) and morbidity.1–3 Incidence rates of SAH have not changed during the CT era, and outcome of SAH has only modestly improved during the past few decades. Outcome is still determined mainly by severity of initial bleeding or early rebleeding.1–4 It seems that identification of preventive treatment methods for aneurysm rupture and of modifiable risk factors for SAH are important as means to influence incidence and outcome of this serious disease. Unruptured aneurysms, when incidentally discovered or found in connection with diagnosis of ruptured aneurysm (multiple aneurysm cases), have been operated on for 2 to 3 decades in western countries. In this way, the high case fatality and morbidity associated with a possible severe initial bleed can be eliminated by preventive surgical intervention. However, the natural history as well as risks of surgery of unruptured intracranial aneurysms are poorly known as are the risk factors for rupture because of lack of studies with sufficient number of patients and follow-up years. The Table shows cohorts of largest studies of rupture risk of unruptured intracranial aneurysms.4–8 The recently published prospective part of The International Study of Unruptured Intracranial Aneurysms (ISUIA; patient enrollment in 61 centers between 1991 and 1998)5 shows somewhat different results as compared with those of the retrospective part of ISUIA (in 53 centers between 1970 and 1991).7 In the prospective study,5 overall incidence of aneurysm rupture was higher (0.8% versus 0.3% per year); risk for rupture of vertebrobasilar aneurysms was lower (relative risk 2.3 versus 5.1 to 13.8 as compared with other aneurysms); mean follow-up time per patient was shorter (3.9 versus 8.3 years); there was a lower limit …

The safety of incidental appendectomy at the time of abdominal hysterectomy

Objective The purpose of this study was to assess the complication rates of incidental appendectomies in women who undergo benign gynecologic procedures. Study design This was a retrospective case-controlled study of patients who did (n = 100 women) or did not (n = 100 women) undergo incidental appendectomies at the time of an abdominal hysterectomy between June 1995 and January 2001. Information was abstracted from hospital and clinic records and a gynecologic oncology database. Data were obtained about age, body mass index, hypertension, diabetes mellitus, the number of days with nothing by mouth, the length of hospital stay, and postoperative complications (cellulitis, fever, ileus, pneumonia, thromboembolic disease). Data were analyzed with the use of two-sample t tests, Wilcoxon Rank sum tests, χ 2 tests, and multiple logistic regressions. Results There was no difference in preoperative diagnosis or operative procedure for either group. The number of patients in the group that did have incidental appendectomy versus the group that did not have incidental appendectomy with additional procedures at the time of abdominal hysterectomy was bilateral salpingo-oophorectomy (66 vs 61 women), unilateral oophorectomy (19 vs 19 women), lysis of adhesions (9 vs 8 women), and others (12 vs 8 women). Compared with the group that did not have incidental appendectomy, the group that did have incidental appendectomy was younger (mean age±SD: 44±9.6 years vs 48±13.6 years, P = .02) and had a lower mean body mass index (26.1±6.0 kg/m 2 vs 29.8±8.9 kg/m 2, P = .0009). No significant differences were found between the two groups (the group that did have incidental appendectomy vs the group that did not have incidental appendectomy, respectively) with respect to the following postoperative complications: fever (40 vs 27 women), cellulitis (1 vs 2 women), wound collection (4 vs 6 women), wound dehiscence (1 vs 5 women), wound abscess (7 vs 6 women), ileus (3 vs 2 women), and urinary tract infection (4 vs 10 women) . The mean length of hospital stay was significantly longer in the group that did have incidental appendectomy than in the group that did not have incidental appendectomy (3.6±1.52 days vs 3.1±1.1 days, P = .006). However, the difference was no longer significant when patients who were fed electively on the postoperative day 2 were excluded from the analysis (3.16±1.13 days vs 3.04±1.13 days, P = .507). Thirty-one percent of the histologic specimens were abnormal, with fibrous obliteration being most common, and there was one case of acute appendicitis. Conclusion An incidental appendectomy at the time of benign gynecologic procedures does not increase postoperative complication rates or length of hospital stay. The inclusion of incidental appendectomies in all abdominal hysterectomies could potentially decrease the morbidity and mortality rates because of appendicitis in elderly women.

Meningitis‐associated hearing loss: Protection by adjunctive antioxidant therapy

Hearing loss is the most frequent long-term complication of pneumococcal meningitis, affecting up to 40% of survivors. Unfortunately, adjuvant therapy with dexamethasone has failed to satisfactorily reduce its incidence. Therefore, we evaluated the use of antioxidants for the adjunctive therapy of meningitis-associated deafness. Eighteen hours after intracisternal injection of 7.5 x 10(5) colony-forming units of Streptococcus pneumoniae, rats were treated systemically either with ceftriaxone and the antioxidants and peroxynitrite scavengers Mn(III)tetrakis(4-benzoic acid)-porphyrin (MnTBAP) or N-acetyl-L-cysteine (NAC) or placebo (1 ml phosphate-buffered saline) for 4 days. Hearing was assessed by auditory brainstem response audiometry. Adjunctive antioxidant therapy significantly reduced the long-term hearing loss (14 days after infection) for square wave impulses (mean hearing loss +/- SD: ceftriaxone and placebo, 45+/-26 dB; ceftriaxone and MnTBAP, 9+/-23 dB; ceftriaxone and NAC, 19+/-30 dB) as well as 1 kHz (ceftriaxone and placebo, 28+/-19 dB; ceftriaxone and MnTBAP, 10+/-16 dB; ceftriaxone and NAC, 10+/-17 dB), and 10 kHz tone bursts (ceftriaxone and placebo, 62+/-27 dB; ceftriaxone and MnTBAP, 16+/-13 dB; ceftriaxone and NAC, 25+/-26 dB). Furthermore, both antioxidants attenuated the morphological correlates of meningogenic hearing loss, namely, long-term blood-labyrinth barrier disruption, spiral ganglion neuronal loss, and fibrous obliteration of the perilymphatic spaces. Adjuvant antioxidant therapy is highly otoprotective in meningitis and therefore is a promising future treatment option.

Pathogenesis and outcome of biliary atresia: current concepts.

Neonatal cholestatic disorders are a group of hepatobiliary diseases occurring within the first 3 months of life. Bile flow is impaired, and patients have conjugated hyperbilirubinemia, acholic stools, and hepatomegaly. Overall, 1 in 2,500 live births is affected with a neonatal cholestatic disorder (1). The two most common causes of neonatal cholestasis are biliary atresia and idiopathic neonatal hepatitis, accounting for up to 50% to 70% of cases. Other causes include a variety of neonatal infections (viral, toxoplasmosis, syphilis, bacterial), metabolic and genetic diseases, progressive familial intrahepatic cholestatic disorders (PFIC), paucity of interlobular bile duct disorders (e.g., Alagille syndrome), choledochal cyst, ischemia–reperfusion injury, association with parenteral nutrition administration, and other conditions (Table 1). Despite clinical improvement after the portoenterostomy procedure, approximately 70% to 80% of children with biliary atresia will eventually require liver transplantation; thus, biliary atresia alone accounts for almost 50% of all liver transplants performed in children (1). It should be noted that $77 million is spent each year in the United States on liver transplantation for children and the ensuing hospitalizations (2). This sum of money covers 0.2% of total health care expenditures related to children, even though these children represent 0.0006% of the total pediatric population. Importantly, this disproportionate expenditure for liver transplantation in children could be cut in half if improved therapies for biliary atresia were developed that could abrogate or further delay the need for liver transplantation. Remarkably, little is known about the etiopathogenesis of biliary atresia; consequently, there has been slow progress in developing improved therapies or preventative strategies during the past decade. The purpose of this review is to summarize recent advances in the diagnosis and management of biliary atresia, examine the clinical outcome, describe the evolving theories of the etiology and pathogenesis of this disorder, and highlight gaps in our current knowledge.

Clinical and Angiographic Results of Intra-Aneurysmal Embolization for Cerebral Aneurysms and Histopathological Findings in an Aneurysm Treated with GDC

We describe follow-up clinical and angiographic results in patients with cerebral aneurysms treated with IDC or GDC. In 175 patients, 116 patients with ruptured aneurysm and 59 patients with non-ruptured aneurysm who underwent endovascular occlusion of aneurysms, there was no mortality and nine cases (4.7%) with morbidity in the periprocedural period. During follow up period, four cases (2.3%) experienced bleeding, and three cases (1.7%) experienced thrombo-embolic events. On the follow-up angiograms (median angiographic follow-up period 24.8 months), 12.5% of incompletely obliterated aneurysms exhibited progressive thrombosis, 20% remained unchanged and 67.5% showed aneurysmal recanalization or regrowth. Histological examination of a small ruptured A-com aneurysm treated seven months before harvesting, demonstrated that formation of an incomplete endothelium- lined layer of connective tissue at the orifice, and no complete fibrous obliteration of the aneurysm lumen could be detected, various amounts of unorganized clot were still present in the center of the aneurysm. Coil embolization is a safe treatment for cerebral aneurysms with a lower incidence of peri-procedural morbidity, wheareas follow-up results are less satisfactory in cases involving incompletely obliterated lesions.

Airway-directed gene transfer of interleukin-10 using recombinant Sendai virus effectively prevents post-transplant fibrous airway obliteration in mice

Bronchiolitis obliterans (BO) after lung transplantation prevents a satisfactory prognosis, and recent studies suggested that interleukin-10 (IL-10) gene transfer to distant organs could inhibit BO in rodent models. Although delivery of the therapeutic gene to a local airway would be favored to minimize systemic effects, current limitations include lower gene transfer efficiency to airway epithelium. As recombinant Sendai virus (SeV) can produce dramatically efficient gene transfer to airway epithelium, we determined if SeV-mediated IL-10 gene transfer to the local airway would inhibit bronchial fibrous obliteration in murine tracheal allografts. Administration of cyclosporine A (CsA) significantly promoted not only recovery of the injured airway epithelium but also SeV-mediated IL-10 expression (CsA- versus CsA+ =228+/-78 versus 3627+/-1372 pg/graft with 5 x 10(7) pfu), thereby suggesting the requirement of epithelia for efficient gene transfer. Even at the highest expression, no significant leakage of IL-10 was evident in the systemic circulation, and the induction of interferon-gamma was completely diminished on day 7 by IL-10 gene transfer. As a result, luminal loss was significantly prevented in allografts treated with SeV-IL-10 (luminal opening, all control groups: 0% respectively, and SeV-IL-10 5 x 10(7) pfu: 25.7+/-10.5%), an effect that was enhanced by short-term CsA treatment (SeV-IL-10 5 x 10(7) pfu with CsA: 63.7+/-12.7%). We propose that SeV is a useful vector that can target airway epithelium to prevent BO avoiding putative systemic effect.

Aortic coarctation in the adult: Management of complications and coexisting arterial abnormalities with hypothermic cardiopulmonary bypass and circulatory arrest

Objectives: Adult patients with aortic coarctation may have complications after childhood repair. Other adult patients have coarctation and aneurysms of the aorta and the left subclavian artery. The optimal management of such cases is not clearly established. We evaluated the role of hypothermic cardiopulmonary bypass and circulatory arrest. Methods: Thirteen adult patients (mean age 38 years) with coarctation and coexisting abnormalities of the aorta and left subclavian artery were treated. Five patients had pseudoaneurysms develop after bypass grafting (n = 3) or patch angioplasty (n = 2). These were detected a mean of 21 years (range 13-44 years) after the initial operation. Four pseudoaneurysms were asymptomatic, and 1 had ruptured. One patient had recurrent coarctation from fibrous obliteration of a 10-mm bypass graft inserted 15 years previously. The remaining 7 patients had aneurysms of the left subclavian artery (n = 5), aneurysms of the ascending aorta and arch (n = 1), or stenosis of the left subclavian artery (n = 1) in combination with moderate or severe coarctation. Resection and interposition graft replacement of the aneurysmal or stenotic aortic segments were performed in all cases with an interval of hypothermic circulatory arrest that averaged 44 ± 5 minutes (range 33-54 minutes). Seven patients had interposition graft replacement of aneurysmal or stenotic left subclavian arteries. Results: There were no in-hospital or late deaths (maximal follow-up 7 years). No patient had brain injury, paralysis, myocardial, respiratory, or renal failure. No patient has evidence of recurrent coarctation or aneurysm formation. Conclusions: Cardiopulmonary bypass with hypothermic circulatory arrest can safely be used in the treatment of complex adult coarctation. It permits accurate delineation of the anatomy with minimal dissection, avoidance of aortic clamping and sacrifice of intercostal arteries, precise interposition graft repair, and adequate protection of vital organs.J Thorac Cardiovasc Surg 2002;124:155-61

Soluble Transforming Growth Factor- β Type III Receptor Gene Transfection Inhibits Fibrous Airway Obliteration in a Rat Model of Bronchiolitis Obliterans

Post-transplant bronchiolitis obliterans (BO) is characterized by fibroproliferation and fibrous obliteration of distal airways in chronically rejected lungs. In this study, using a rat heterotopic allogeneic tracheal transplant model of BO, we evaluated the expression of transforming growth factor-beta (TGFbeta) during the development of airway fibrous obliteration. Immunohistochemical analysis revealed TGFbeta staining in infiltrating mononuclear cells at Days 2 and 7, and in the fibrous tissues until Day 21. Soluble TGFbeta receptor type III (TGFBIIIR), by blocking TGFbeta binding to its membrane receptors, functions as a TGFbeta antagonist. To study the role of TGFbeta in the development of BO, adenoviral-mediated soluble TGFBIIIR gene transfection (5 x 10(9) particles) was performed topically at the site of transplant on Day 5 after transplantation, which leads to inhibition of fibrous airway obliteration. In contrast, empty vector gene delivered through intramuscular injection, or given locally at Days 0 or 10 after tracheal transplantation had no significant effect. These results suggest that TGFbeta expressed in the allografts plays a pivotal role in the pathogenesis of BO. Soluble TGFBIIIR may competitively inhibit TGFbeta activity locally. Adenoviral-mediated soluble TGFBIIIR gene transfection should be further explored as a potential therapeutic modality for BO and other conditions involving chronic fibrosis.

Appendiceal Disease in Women with Endometriosis and Right Lower Quadrant Pain

Study ObjectiveTo evaluate the frequency and range of appendiceal disease in women with endometriosis and right lower quadrant (RLQ) pain, and to estimate the value of preoperative gastrograffin enema (GGE) as a screen for the disease. DesignNonrandomized clinical trial (Canadian Task Force classification II-2). SettingUniversity-affiliated hospital with a private practice setting. PatientsA subpopulation of 65 women from a group of 337 patients undergoing laparoscopy for symptomatic endometriosis. InterventionsPreoperative GGE was performed whenever possible in these women. At laparoscopy, the appendix was removed if it appeared abnormal or if the preoperative GGE was positive. Measurements and Main ResultsOf 65 women (19%) with symptomatic endometriosis and preoperative RLQ pain, 52 (80%) underwent appendectomy as part of surgery. Of these 52 excised appendixes, 39 (75%) had histologically confirmed pathology including appendicitis or periappendicitis, endometriosis, fibrous obliteration, lymphoid hyperplasia, and carcinoid tumor. Preoperative GGE had sensitivity of 74% and specificity of 83% for appendiceal disease. Its positive predictive value was 95% and negative predictive value was 42%. No complications from laparoscopic appendectomy occurred. ConclusionDisease of the appendix is common in women with endometriosis and RLQ pain. Appendectomy is particularly likely if preoperative GGE is positive.

Appendectomy in Patients Undergoing Laparoscopic Surgery for Pelvic Pain

Study ObjectiveTo evaluate pathologic findings in appendixes of women undergoing laparoscopic surgery for pelvic pain. DesignRetrospective study (Canadian Task Force classification II-2). SettingPrivate practice specializing in gynecologic endoscopic surgery. PatientsOne hundred ninety women. InterventionProphylactic appendectomy Measurements and Main ResultsOn pathologic evaluation, 154 appendixes were diagnosed as having one or more abnormal findings, such as endometriosis, carcinoid, chronic appendicitis, periappendicitis, fibrous obliteration, and lymphoid hyperplasia. ConclusionWomen undergoing laparoscopic surgery for pelvic pain should be counseled on the high frequency of abnormal findings in the appendix, including endometriosis. Prophylactic appendectomy appears to be a worthwhile consideration in these patients.