In 1990, an international grading scheme for the grading of pulmonary allograft rejection was adopted by the International Society for Heart and Lung Transplantation (ISHLT) and was modified in 1995 by an expanded group of pathologists. The original and revised classifications have served the lung transplant community well, facilitating communication between transplant centers with regard to both patient management and research. In 2006, under the direction of the ISHLT, a multi-disciplinary review of the biopsy grading system was undertaken to update the scheme, address inconsistencies of use, and consider the current knowledge of antibody-mediated rejection in the lung. This article summarizes the revised consensus classification of lung allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates, Grade A0 (none), Grade A1 (minimal), Grade A2 (mild), Grade A3 (moderate) and Grade A4 (severe), as previously. The revised (R) categories of small airways inflammation, lymphocytic bronchiolitis, are as follows: Grade B0 (none), Grade B1R (low grade, 1996, B1 and B2), Grade B2R (high grade, 1996, B3 and B4) and BX (ungradeable). Chronic rejection, obliterative bronchiolitis (Grade C), is described as present (C1) or absent (C0), without reference to presence of inflammatory activity. Chronic vascular rejection is unchanged as Grade D. Recommendations are made for the evaluation of antibody-mediated rejection, recognizing that this is a controversial entity in the lung, less well developed and understood than in other solid-organ grafts, and with no consensus reached on diagnostic features. Differential diagnoses of acute rejection, airway inflammation and chronic rejection are described and technical considerations revisited. This consensus revision of the working formulation was approved by the ISHLT board of directors in April 2007.

Revision of the 1990 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Heart Rejection

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Pathology and genetics of tumours of the lung , pleura, thymus and heart

Overall survival rates of lung transplantation have improved since the first human lung transplantation was performed. A decline in the incidence of airway complications (AC) had been a key feature to achieve the current outcomes. Several proposed risk factors to the development of airway complications have been identified, ranging from the surgical technique to the immunosuppressive regimen. There are essentially six different airway complications post-lung transplantation. The most frequently reported complication is bronchial stenosis. Other complications include bronchial dehiscence, exophytic excessive granulation tissue formation, tracheo-bronchomalacia, bronchial fistulas, and endobronchial infections. The management of post-transplant bronchial complications needs a multispecialty team approach. Prevention of some complications may be possible by early and aggressive medical management as well as by using certain surgical techniques for transplantation. Interventional bronchoscopic procedures, including balloon bronchoplasty, cryotherapy, laser photoresection, electrocautery, high-dose endobronchial brachytherapy, and bronchial stents are among the armamentarium. Also, medical management, like antibiotic prophylaxis and therapy for endobronchial infections, or noninvasive positive-pressure ventilation in case of bronchomalacia, are used to treat an AC. In some cases, different surgical approaches are occasionally required. In this article we review the risk factors, the clinical presentation, the diagnostic methods, as well as the management options of the most common AC after lung transplantation.

Airway complications and management after lung transplantation: ischemia, dehiscence, and stenosis.

Bronchus-associated lymphoid tissue (BALT) was first described in the lungs of rabbits and differs greatly between species. It is part of the integrated mucosal immune system. This review clarifies its morphological definition and focuses on the situation in humans. The frequency of BALT at different ages, after chronic stimulation and in different diseases is described. In healthy humans, BALT can only be found in the lungs of children and adolescents. The role of BALT in lung transplantation and in the development of low-grade malignant lymphomas in the airways is also discussed. Furthermore, questions concerning the inducibility of BALT as an entry site for vaccines, and the regulation of its activity for future therapeutic interventions in pulmonary immune reactions are addressed.

Bronchus-Associated Lymphoid Tissue (BALT) Is Not Present in the Normal Adult Lung but in Different Diseases

Biological correlates of FDG uptake in non-small cell lung cancer

Background: Descending necrotizing mediastinitis resulting from oropharyngeal abscess, is a serious, life-threatening infection. Exisiting strategies for surgical management, such as transcervical mediastinal drainage or aggressive thoracotomic drainage, remain controversial.Methods: Four patients, (three males and one female) were treated for descending necrotizing mediastinitis resulting from oropharyngeal infection. Two had peritonsillar abscesses, while the others experienced dental abscess and submaxillaritis. Descending necrotizing mediastinitis received its classification according to the degree of diffusion of infection diagnosed by computed tomography. Mediastinitis in two cases, (Localized descending necrotizing mediastinitis-Type I), was localized to the upper mediastinal space above the carina. In the others, infection extended to the lower anterior mediastinum (Diffuse descending necrotizing mediastinitis-Type IIA), and to both anterior and posterior lower mediastinum (Diffuse descending necrotizing mediastinitis-Type IIB). The spread of infection to the pleural cavity occurred in three cases.Results: The surgical outcome concerning each of the patients was successful. Radical cervicotomy (unilateral in three patients, bilateral in the other) in conjunction with mechanical ventilation with continuous postoperative positive airway pressure, was performed in all cases. Tracheostomy was established in three patients and pharyngostomy in two. The two descending necrotizing mediastinitis-Type I cases were successfully managed with transcervical mediastinal drainage. The descending necrotizing mediastinitis-Type IIA case received treatment through transcervicotomy and anterior mediastinal drainage through a subxiphoidal incision. The patient with descending necrotizing mediastinitis-Type IIB required posterior mediastinal drainage through a right standard thoracotomy followed by left minimal thoracotomy.Conclusions: The mediastinal infection, the extent of which has been accurately determined by computed tomograms, necessitates radical cervicotomy followed by pleuromediastinal drainage. Situations where infection has spread to posterior mediastinum, particularly when it reaches in the level of the carina (descending necrotizing mediastinitis-type I), may not always require aggressive mediastinal drainage. In comparison, diffuse descending necrotizing mediastinitis-Type IIB demands complete mediastinal drainage with debridement via thoracotomy. Subxiphoidal mediastinal drainage without sternotomy may provide adequate drainage in diffuse descending necrotizing mediastinitis-Type IIA.

Guideline of surgical management based on diffusion of descending necrotizing mediastinitis

Pulmonary tumorlets are minute neuroendocrine cell proliferations believed to be precursor lesions to pulmonary carcinoids. Little is known of their molecular pathogenesis because of their small size. Using tissue microdissection, we evaluated 11q13 region allelic imbalance in the pathogenesis of pulmonary tumorlet/carcinoid lesions. The int-2 gene was selected because of its chromosomal location at 11q13 in close proximity to MEN1, a tumor suppressor gene frequently mutated in familial forms of neuroendocrine cancer. Three cohorts of patients were studied: subjects with typical carcinoid tumors and coexisting tumorlets (n = 5), typical carcinoids without tumorlets (n = 6), and tumorlets alone without carcinoid lesions (n = 5). A total of 11 carcinoids and 11 tumorlets were microdissected from 4-μm-thick histological sections. Genotyping was designed to detect allelic imbalance of the int-2 gene and involved DNA sequencing of two closely spaced deoxynucleotide polymorphisms. Subjects shown to be informative were evaluated for allelic imbalance in tumorlet/carcinoid tissue. Eight of 11 (73%) carcinoids manifested allelic, in contrast to only one of 11 (9%) of tumorlets. Int-2 allelic imbalance was significantly associated with carcinoid tumor formation (P < 0.01). In patients having both carcinoid tumors and tumorlets, the latter showed allelic balance and were thus discordant in genotype with coexisting carcinoid excluding pathogenesis of tumorlets from intramucosal spread from carcinoid tumors. Int-2 allelic imbalance was shown to be an early event in carcinoid tumor formation by virtue of the absence of allelic imbalance for other common cancer-related gene disturbances involving 11p13 (Wilms’ tumor), 3p25 (von-Hippel-Lindau), and 17p13 (p53). Demonstration of 11q13 allelic imbalance by microdissection/genotyping may be a useful discriminatory marker for pulmonary neuroendocrine neoplasia.

11q13 allelic imbalance discriminates pulmonary carcinoids from tumorlets. A microdissection-based genotyping approach useful in clinical practice.

Objective: Massive hemoptysis is a life-threatening condition. Surgery is effective but we are sometimes reluctant to operate on patients with this condition. We reviewed our experience with patients who underwent emergency surgery for massive hemoptysis to verify the indications for non-emergency surgical intervention. Methods: We reviewed chest computed tomography (CT) and angiographic and pathological findings and the postoperative course of 25 patients who underwent emergency pulmonary resection in our department between 1979 and 2001 due to life-threatening hemoptysis. Results: CT revealed a persistent cavity within the radiological opacity before massive hemoptysis in 12 patients (48%). Of the 21 patients who underwent angiography, nine showed focal bleeding in one bronchial branch and the others showed bleeding in multiple branches. Of these nine patients, seven did not undergo embolotherapy mainly due to minor vascularity. In the remaining patients, embolotherapy was not indicated in six due to multiple bleeding feeders and recurrence after embolotherapy was seen in six. Pathological findings showed that eight of the 12 patients with multiple systemic shunts had a fungal infection. Operative morbidity and hospital mortality were 32 and 4%, respectively. There was no recurrence in patients who underwent surgical treatment. Conclusions: Early pulmonary resection is indicated in patients with hemoptysis of multiple branches from the cavity and chest wall, such as in fungal infections. When a bronchial branch is the only bleeding focus, superselective embolotherapy should be considered prior to surgery even if the localized focus of the bronchial branch shows minor vascularity on the angiography. q 2003 Elsevier Science B.V. All rights reserved.

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Management of massive hemoptysis in a thoracic surgical unit

https://www.annalsthoracicsurgery.org/article/S0003-4975(99)01556-8/pdf

Segmental nonanastomotic bronchial stenosis after lung transplantation.

Objectives: Bronchogenic cysts of the mediastinum are rare congenital anomalies that arise early in gestation from abnormal budding of the developing respiratory system. Recommended treatment is surgical resection and incomplete resection may lead to local recurrence more than 10 years later with or without various symptoms. Methods: We reported a case and reviewed literatures. Results: A case of a recurrent bronchogenic cyst in a 42-year-old man 15 years after first resection is presented. The patient had a persistent high fever resistant to antibiotic therapy. Magnetic resonance imaging and subsequent thoracotomy revealed a recurrent bronchogenic cyst. This case illustrates that incompletely resected mediastinal bronchogenic cyst may recur with later symptoms. Conclusions: Recommended treatment for bronchogenic cysts is complete surgical excision. q 2003 Elsevier B.V. All rights reserved.

Tsuyoshi Hasegawa

Papers

Guideline of surgical management based on diffusion of descending necrotizing mediastinitis

11q13 allelic imbalance discriminates pulmonary carcinoids from tumorlets. A microdissection-based genotyping approach useful in clinical practice.

Management of massive hemoptysis in a thoracic surgical unit

Segmental nonanastomotic bronchial stenosis after lung transplantation.

Negative results - Thoracic general Recurrent bronchogenic cyst 15 years after incomplete excision