Trends in extramural consultation: comparison between subspecialized and general surgical pathology service models.

Academic and community hospital pathology groups are increasingly adopting subspecialized service models for surgical pathology (SP) practice. Reasons cited include improvements in sign-out efficiency, quality and accuracy, enhancement of clinician-pathologist communications, and augmentation of resident training quality. However, there is a paucity of published quantitative data regarding the outcomes of transitioning from general to subspecialized SP service coverage. Retrospective assessment of the frequencies and outcomes of SP extramural consultations requested by faculty at our institution was performed, encompassing 2 consecutive years each of subspecialized and general SP service models. The frequencies of extramural consultations between the 2 practice models were not significantly different (0.25% vs 0.21%, P = .142). Although more pathology cases were sent out in gastrointestinal (0.29% vs 0.14%, P = .007), gynecologic (0.16% vs 0.02%, P = .009), and pulmonary (1.73% vs 0.28%, P = .008) services during the "subspecialization" era, fewer pediatric cases were sent out (0.48% vs 1.69%, P = .008). Importantly, the transition to the subspecialized model was associated with a marked reduction in the frequency of major disagreements between the original diagnosis and the consultant's diagnosis (1.8% vs 9.3%, P = .018). Our study supports the value of the subspecialized SP sign-out model for increasing diagnostic accuracy and enhancing the quality of patient care.

Immune functional assay for immunosuppressive management in post-transplant malignancy.

Immunosuppression management in post-transplant malignancy is challenging because of a lack of objective immunologic assessment tools. The ImmuKnow assay measures the ATP level from CD4 T cells, quantifying cell-mediated immunity and providing an insight into the immune status of transplant recipients. Its potential use in patients with post-transplant de novo malignancy was evaluated. Thirteen adult transplant patients with de novo malignancy were divided into survivors (n = 9) and non-survivors (n = 4) after malignancy treatment. Tacrolimus and the ImmuKnow levels were monitored before, during, and after malignancy treatment. The ImmuKnow level in non-survivors group was significantly lower before and after malignancy treatment compared to survivors group (p = 0.013 and 0.0014 respectively). In survivor group, the ImmuKnow level was significantly decreased during malignancy treatment (p = 0.019) but recovered to the initial level after the treatment. However, in non-survivor group, the ImmuKnow level remained suppressed throughout the observed period despite a reduction in immunosuppressive drug levels. The ImmuKnow assay can be an objective means evaluating immune status of patients with de novo malignancy. The ImmuKnow assay can express the degree of immune suppression induced by chemotherapeutic or radiation therapy and may be a useful tool in optimizing the timing of re-introduction of immunosuppression after malignancy treatment.

Women in Academic Pathology: Pathways to Department Chair.

The Association of Pathology Chairs, an organization of American and Canadian academic pathology departments, has a record percent of women department chairs in its ranks (31%), although still not representative of the percent of women pathology faculty (43%). These women chairs were surveyed to determine what had impeded and what had facilitated their academic advancement before becoming chairs. The 2 most frequently identified impediments to their career advancement were heavy clinical loads and the lack of time, training, and/or funding to pursue research. Related to the second impediment, only one respondent became chair of a department which was in a top 25 National Institutes of Health-sponsored research medical school. Eighty-nine percent of respondents said that they had experienced gender bias during their careers in pathology, and 31% identified gender bias as an important impediment to advancement. The top facilitator of career advancement before becoming chairs was a supportive family. Strikingly, 98% of respondents have a spouse or partner, 75% have children, and 38% had children younger than 18 when becoming chairs. Additional top facilitators were opportunities to attend national meetings and opportunities to participate in leadership. Previous leadership experiences included directing a clinical service, a residency training program, and/or a medical student education program. These results suggest important ways to increase the success of women in academic pathology and increasing the percent of women department chairs, including supporting a family life and providing time, encouragement and resources for research, attending national meetings, and taking on departmental leadership positions.

Molecular discrimination of multiple primary versus metastatic squamous cell cancers of the head/neck and lung.

Patients with squamous cell carcinoma (SqCa) arising in the head and neck (H/N) commonly develop solitary pulmonary metastases that mimic the clinical, radiographic, and pathologic presentation of new primary lung SqCa. Primary pulmonary and metastatic SqCas cannot be differentiated from each other histologically. However, distinguishing multiple independent primary neoplasms from a primary H/N SqCa with pulmonary metastasis has prognostic significance due to its impact on tumor stage, the most important determinant of prognosis. Since genomic instability is a common feature of cancer, we hypothesized that independently-arising neoplasms in an individual patient would exhibit measurable genomic variation, enabling discrimination of tumor lineage and relatedness. In this study, we describe a molecular approach for analysis of genetic variation among multiple tumors from a single patient that does not rely on collection of normal tissue, and which can be performed with minimal tumor samples. Genomic DNA from H/N and lung SqCas from individual patients were analyzed by microsatellite PCR to identify discordant allelic variation. This method is rapid, sensitive, does not require constitutional DNA for comparison, and can be applied to the analysis of archival tumor DNA. Our results demonstrate that microsatellite PCR can identify discordant genetic variation among multiple tumors from a single patient, facilitating the molecular discrimination of metachronous primary SqCa versus solitary pulmonary metastasis from a H/N primary SqCa.

The Association of Pathology Chairs' Pathology Leadership Academy: Experience From the First 2 Years.

Leadership development and succession planning are critical to ensure continued strength of academic pathology. The Association of Pathology Chairs developed the Pathology Leadership Academy to prepare future academic leaders. The purpose of this report is to describe: (1) Pathology Leadership Academy's development and curriculum, (2) how Pathology Leadership Academy has met leadership development needs for individuals and academic departments in its first 2 years, (3) Pathology Leadership Academy's future directions based on program feedback. Results were analyzed from pre- and postprogram needs assessment surveys of pathology chairs and from evaluations from Pathology Leadership Academy participants in the first 2 years. Pathology Leadership Academy curriculum was developed from topics identified as priorities in the chairs' survey. Twenty-eight (90%) of 31 responding participants were very satisfied/satisfied with Pathology Leadership Academy. Of the 18 responding chairs who sent a participant to Pathology Leadership Academy, 11 (61%) reported that Pathology Leadership Academy met their faculty development goal. Of all responding chairs, 13 (32%) of 41 reported uncertainty as to whether Pathology Leadership Academy is meeting chairs' goals. Chairs reported that Pathology Leadership Academy provided value to their faculty through preparation for a future leadership role, enhancing skills for a current role, and enhancing understanding of opportunities and challenges in academic medicine. Most chairs (27/43, 66%) said Pathology Leadership Academy should be offered again; 13 (32%) of 43 were uncertain, and 1 (2%) of 43 said no. Initial experience of Pathology Leadership Academy is positive and promising and provides opportunity for leadership succession planning in academic pathology. Pathology Leadership Academy will use participant and chair feedback for ongoing curricular development to ensure topics continue to address major needs of academic pathology.

ALDH1A1 and ALDH3A1 expression in lung cancers: correlation with histologic type and potential precursors.

We hypothesize that aldehyde dehydrogenase (ALDH) isozymes may be upregulated in lung tissue as a result of exposure to carcinogenic aldehydes found in cigarette smoke. To investigate this hypothesis, we studied the expression of two ALDH isozymes in lung cancer from patient samples and its relationship to the history of cigarette smoking. Immunohistochemical staining for ALDH1A1 and ALDH3A1 was performed on archival specimens from control patients without lung cancer, and patients with one of the primary lung cancers: squamous cell cancer (SCCA), adenocarcinoma (AdenoCA), and small cell lung cancer (SCLC). An overall score was obtained for each sample based upon multiplying the staining intensity (0-3) and the extensiveness (0-100%). Mean+/-S.E.M. for each experimental group was calculated and compared. Our results indicate a significantly higher level of expression of ALDH1A1 and ALDH3A1 in SCCA (155+/-19 and 162+/-17, respectively) and AdenoCA (116+/-12 and 107+/-10) than SCLC (39+/-11 and 42+/-12) (P<0.01). Atypical pneumocytes demonstrated significantly higher levels of expression of ALDH1A1 and ALDH3A1 than normal pneumocytes (a normal counterpart of AdenoCA), which is suggestive of up regulation during malignant transformation to AdenoCA. A subset analysis of all samples studied revealed increased expression of ALDH1A1 (P=0.055) and ALDH3A1 (P=0.0093) in normal pneumocytes of smokers (n=32) in comparison to those of non-smokers (n=17). Non-small cell lung cancer (NSCLC) express very high levels of ALDH1A1 and ALDH3A1 in comparison with SCLC, elevated expression of both enzymes may be associated with malignant transformation to AdenoCA, and cigarette smoking seems to result in increased expression of these enzymes in normal pneumocytes.

The Pathology Workforce and Clinical Licensure: The Role of the PhD Clinical Laboratorian in the United States.

There has been a recent recognition of the need to prepare PhD-trained scientists for increasingly diverse careers in academia, industry, and health care. The PhD Data Task Force was formed to better understand the current state of PhD scientists in the clinical laboratory workforce and collect up-to-date information on the training and certification of these laboratorians. In this report, we summarize the findings of the PhD Data Task Force and discuss the relevance of the data collected to the future supply of and demand for PhD clinical laboratory scientists. It is clear that there are multiple career opportunities for PhD scientists in academic medical centers, commercial clinical laboratories, biotechnology and pharmaceutical companies, and the federal government. Certified PhD scientists have and will continue to form an important resource for our technologically advancing field, bringing training in scientific methods, and technologies needed for modern laboratory medicine. The data gathered by the PhD Data Task Force will be of great interest to current and future PhD candidates and graduate PhD scientists as they make decisions regarding future career directions.

Expression of glutathione S-transferase pi and glutathione synthase correlates with survival in early stage non-small cell carcinomas of the lung.

The glutathione S-transferase (GST) family of genes encode for detoxification enzymes that protect against reactive oxygen species and influence host susceptibility to carcinogens, including tobacco smoke. It has not been determined whether isoenzyme GST-pi or glutathione synthase (GSH2) expression by tumor cells bears a relationship to survival. A total of 201 non-small cell lung cancers (NSCLC) with long-term follow-up were immunostained with antibodies to GST-pi and GSH2 using standard immunostaining techniques. Results were graded semiquantitatively using a scale of 0 to 3 (0 < or = 10%; 1 = 10%-50%; 2 = 51%-80%; 3 > or = 80%) for both nuclear and cytoplasmic staining. Results were correlated with patient survival using Kaplan-Meier analysis. Nuclear staining with GST-pi in greater than 10% of the cells was closely associated with decreased survival (P = .02) in stage I and II squamous cell carcinomas (n = 40). Cytoplasmic staining showed a similar trend that did not reach statistical significance. No significant correlation between GST-pi staining and survival was determined for other histologic types of NSCLC. Cytoplasmic GSH2 staining in greater than 80% of tumor cells was associated with a trend toward improved survival for stage I adenocarcinoma (P = .08) but did not show a relationship to survival for other histologic types of NSCLC. GST-pi expression predicts prognosis in stage I and II squamous cell lung carcinoma, and GSH2 expression may indicate better survival in early stage adenocarcinoma of the lung. Manipulation of GST-pi and GSH2 may be a potential basis for treatment of some NSCLC.

Pneumonic-type mucinous lung adenocarcinoma diagnosed by transbronchial cryobiopsy.

Primary lung adenocarcinoma with lepidic growth can mimic diffuse pulmonary parenchymal processes like infectious pneumonia or idiopathic inflammatory pneumonitis. We report a case of subacute pneumonitis refractory to antibiotic therapy and empirical corticosteroids, proven to be diffuse mucinous adenocarcinoma with lepidic growth on transbronchial cryobiopsy.

Biologic Evaluation of Diabetes and Local Recurrence in Non-Small Cell Lung Cancer.

A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers. Seventy-nine NSCLC patients were selected from the cohort of our early multicenter study. These patients were classified into 4 groups: 39 with adenocarcinoma with (n = 19) and without (n = 20) diabetes, and 40 with squamous cell carcinoma with (n = 20) and without (n = 20) diabetes. Immunohistochemical expression of eight EMT markers was analyzed, including transforming growth factor-beta (TGF-ß), epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), vimentin, E-cadherin, N-cadherin, HtrA1, and beta-catenin. Five markers (E-cadherin, HtrA1, TGF-ß, IGF-1R and vimentin) demonstrated significantly higher expression in diabetics than in non-diabetics in both histology types. N-cadherin had higher expression in diabetics, though the difference did not reach statistical significance. EGFR showed a higher expression in diabetics in squamous cell carcinoma only. Beta-catenin was the only marker with no difference in expression between diabetics versus non-diabetics. Our findings suggest that diabetes is associated with enhanced EMT in NSCLC, which may contribute to growth and invasiveness of NSCLC.

Donor-derived type II pneumocytes are rare in the lungs of allogeneic hematopoietic cell transplant recipients.

Lung injury is a common cause of death and disability. Stem cell-related therapies are widely viewed as offering promise for people suffering from various types of pulmonary diseases, and gender-mismatched bone marrow transplant recipients serve as natural populations in which to study the role of bone marrow-derived stem cells in recovery from pulmonary injury. We evaluated the extent of lung repopulation by type II pneumocyte descendents of adult bone marrow-derived stem cells in allogeneic hematopoietic cell transplant recipients. Recut sections were obtained from five lung biopsy specimens and autopsy lung tissues from four female recipients of transplanted mobilized peripheral blood stem cells or bone marrow from male donors. Sequential immunohistochemistry and fluorescence in situ hybridization was performed on each section to evaluate for Y-chromosome-containing type II pneumocytes. A single Y-chromosome-containing type II pneumocyte was found in one lung biopsy from one hematopoietic cell transplant recipient. After adjustment for the effects of incomplete nuclear sampling, this pneumocyte represented 1.75% of all type II pneumocytes in the biopsy sample. There was no evidence of polyploidy to suggest cell-to-cell fusion. No donor-derived type II pneumocytes were found in samples from the other three patients. In conclusion, repopulation by bone marrow-derived stem cells or their progeny occurs at a low frequency in the lungs of hematopoietic cell transplant recipients. Conversely, proliferation by local stem cell populations appears to be more important for recovery from alveolar injury.

Assessment of cytotechnologist-cytopathologist interpretative agreement using the Bethesda system for reporting thyroid cytopathology.

BACKGROUND: The Bethesda system for reporting thyroid cytopathology was proposed to provide a clinically relevant framework for interpretations to improve interobserver agreement. Limited data is available regarding the level of interobserver agreement between groups of cytotechnologists (CTs) and cytopathologists (CPs) examining the same thyroid fine needle aspirate (FNA) samples. METHODS: Retrospective review of 1,229 thyroid FNAs from 976 patients between 03/2010 and 08/2012 was performed. FNAs received preliminary evaluation by a CT followed by final interpretation by a CP. We calculated Cohen's Kappa coefficient to measure agreement between CTs and CPs, and analyzed levels of discrepancy using delta analysis. RESULTS: Overall Kappa between CTs and CPs was 0.79 (95%CI: 0.76-0.83). Kappa values were higher for the nondiagnostic (0.89), benign (0.83), and malignant (0.91) categories than for other categories. Overall Kappa did not show a trend over time, and inversely correlated with the percentage of intermediate grade lesions (coefficient of -0.8; P < 0.01). CTs overcalled more cases (n = 71) than undercalled (n = 29) (P < 0.001), as compared to CPs, with a Δ1 ratio of 2.2 and Δ2 ratio of 3.5. Most two-level discrepancies were related to follicular lesions (19/21) (P = 0.0002). Differences in sample adequacy assessment occurred in 2% of cases. CONCLUSION: Overall, there was a high level of interpretative agreement between CTs and CPs, which remained stable over time, including judgments regarding specimen adequacy. Agreement was most robust for the benign and malignant categories. Our data supports the current practice of allowing CTs to perform on-site adequacy evaluation of thyroid FNAs.

Bone marrow transdifferentiation in brain after transplantation: a retrospective study.

BACKGROUND: End-organ repair by adult haemopoietic stem cells is under great scrutiny with investigators challenging the notion of these cells' plasticity. Some investigations of animals and short-term human bone marrow transplants suggest that bone marrow can repair brain. We looked for evidence of clinically relevant marrow-derived restorative neurogenesis: long-term, multilineage, neural engraftment that is not the result of cell-fusion events. METHODS: We examined autopsy brain specimens from three sex-mismatched female bone-marrow-transplantation patients, a female control, and a male control. We did immunohistochemistry, fluorescence in-situ hybridisation, and tissue analysis to look for multilineage, donor-derived neurogenesis. FINDINGS: Hippocampal cells containing a Y chromosome were present up to 6 years post-transplant in all three patients. Transgender neurons accounted for 1% of all neurons; there was no evidence of fusion events since only one X chromosome was present. Moreover, transgender astrocytes and microglia made up 1-2% of all glial cells. INTERPRETATION: Postnatal human neuropoiesis happens, and human haemopoietic cells can transdifferentiate into neurons, astrocytes, and microglia in a long-term setting without fusing. Transplantable human haemopoietic cells could serve as a therapeutic source for long-term regenerative neuropoiesis.

Bone marrow-derived stem-cell repopulation contributes minimally to the Type II pneumocyte pool in transplanted human lungs.

BACKGROUND: Lung transplant recipients are vulnerable to immunologic, infectious, ischemic, and toxic pulmonary injuries. The authors investigated whether type II pneumocytes in the lungs of cross-gender lung transplant patients show genotypic evidence to support repopulation of the lung by stem cells of bone marrow origin, and whether the degree of repopulation was related to rejection history. METHODS: Recut sections were obtained from lung biopsy specimens from seven male recipients of transplanted lungs from female donors. Sequential immunohistochemistry and fluorescence in situ hybridization was performed on each section to evaluate for Y-chromosome-containing type II pneumocytes. RESULTS: Y-chromosome-containing type II pneumocytes were found in 9 of 25 biopsy specimens from 5 of 7 gender-mismatched male lung transplant recipients, and accounted for 0% to 0.553% of type II pneumocytes. There was no evidence of polyploidy to suggest cell-cell fusion. The number of type II pneumocytes of male karyotype showed a statistically significant relationship to the cumulative number of episodes of acute cellular rejection. CONCLUSIONS: Lung transplant recipients develop low levels of pneumocyte repopulation by bone marrow-derived stem cells or their progeny. These cells contribute minimally to the type II pneumocyte proliferation that is often present in these patients as a sequela to alveolar injury.

Graft protective effects of heme oxygenase 1 in mouse tracheal transplant-related obliterative bronchiolitis.

BACKGROUND: Heme oxygenase (HO)-1, long believed to be a cytoprotective protein, has recently been identified as a graft survival gene. This study evaluates the role of HO-1 in a murine heterotopic tracheal allograft model for obliterative bronchiolitis. METHODS: Mice with deficient or experimentally enhanced HO-1 expression underwent subcutaneous implantation of murine tracheal isografts and allografts. Grafts were excised after 9, 16, or 21 days and evaluated by histologic examination, immunohistochemistry for HO-1 and interleukin (IL)-10 proteins, and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. To evaluate the relationships between IL-10 and HO-1, the effects of modulation of HO-1 expression on IL-10 expression were evaluated and HO-1 expression was examined in tracheal transplants from IL-10 null mice. RESULTS: Isografts demonstrated normal histology with minimal HO-1 staining, whereas allografts showed features of human airway rejection (loss of respiratory epithelium, luminal granulation tissue, lymphocytic tracheitis) with increased HO-1 staining in macrophages and mesenchymal cells. HO-1-deficient mice demonstrated a more rapid progression of the tracheal allograft injury as compared with control allografts, and this was associated with a decrease in the anti-inflammatory cytokine, IL-10. Tracheal transplants using IL-10-deficient mice also resulted in a more severe injury, and this was accompanied by a decrease in HO-1 staining. CONCLUSIONS: HO-1 protein expression is increased in murine heterotopic airway rejection, and deficiency of HO-1 accelerates the development of the obliterative bronchiolitis-like lesion. IL-10 protein expression parallels expression of HO-1, suggesting that IL-10 may participate in the genesis of HO-1's effects on the inflammatory processes triggered by allotransplantation.

Mesalamine-related lung disease: clinical, radiographic, and pathologic manifestations.

Lung injury related to mesalamine (5-aminosalicylic acid) has rarely been reported in patients with inflammatory bowel diseases. Patients present with progressive respiratory symptoms and radiographic abnormalities whose genesis may occur from days to years after initiation of therapy. Although pathologic features overlap with other pulmonary disorders, findings of chronic interstitial pneumonia and poorly formed nonnecrotizing granulomas should prompt consideration of mesalamine-related lung disease in a patient receiving this medication. The authors describe the clinical, radiographic, and pathologic manifestations of mesalamine-related lung disease in three patients and review the literature related to this topic.

Role of transbronchial biopsies in pediatric lung diseases.

STUDY OBJECTIVE: To evaluate the role of transbronchial biopsies (TBBs) in pediatric lung diseases. DESIGN AND METHODS: We reviewed the records of TBBs performed in pediatric patients at the University of Florida between July 1996 and August 2003. The sample adequacy, diagnostic utility, and procedural complications of the two types of bronchoscopy apparatuses used to collect the samples were assessed and compared. PATIENTS: A total of 429 TBB procedures were performed in 46 patients (age range, 2 months to 21 years) who had received a heart-lung or lung transplant and in 38 non-lung transplant patients (age range, 2 weeks to 18 years). For 86 procedures, the pediatric bronchoscope and forceps that fit in a 1.2-mm channel were used, and a small adult bronchoscope and 2.0-mm forceps were used for the remaining procedures. RESULTS: Adequate tissue samples were obtained in 85% of the procedures using a pediatric bronchoscope and in 97% using an adult bronchoscope. In the non-lung transplant patients, the biopsy findings were considered to be diagnostic in 58% of all procedures (adult bronchoscope, 64%; and pediatric bronchoscope, 50%), contributory in 21%, and noncontributory in 21%. In the lung transplant patients, treatable acute cellular rejection was diagnosed in 24% of the surveillance TBBs and in 47% of the TBBs performed as a result of clinical symptoms. Complications included five pneumothoraces and five episodes of excessive bleeding requiring the discontinuation of the procedure in three of the cases. CONCLUSIONS: Adequate lung tissue for histologic diagnosis can be obtained safely and effectively from pediatric patients of all ages via flexible bronchoscopy with TBB. The performance of bronchoscopy should be considered based on clinical indications, rather than on the age or size of the patient, when a tissue diagnosis is needed. When feasible, the use of an adult bronchoscope is preferable due to the higher diagnostic yield.

Increased expression of heme oxygenase-1 in human lung transplantation.

Heme oxygenase-1 (HO-1) has been found to be a cytoprotective protein, and has recently been identified as a graft survival gene. This study demonstrates that HO-1 expression is increased in human lung allografts with acute cellular rejection and obliterative bronchiolitis. HO-1 expression was correlated with increased tissue iron and/or ferritin expression and increased inflammatory/oxidant load as measured by myeloperoxidase expression. Although the trigger for increased HO-1 expression in this setting is unknown, it may be related to hemorrhage and/or oxidative stress associated with rejection.

Heme-oxygenase-1 expression correlates with severity of acute cellular rejection in lung transplantation.

BACKGROUND: Heme-oxygenase-1 (HO-1) has been shown to play an important role in oxidative stress, and recent studies indicate that it is a graft survival protein in cardiac and liver transplant models. Our laboratory previously found HO-1 to be increased in human lung allografts with acute cellular rejection (ACR) and in active obliterative bronchiolitis. To better understand the role of HO-1 in ACR we studied the relationship between HO-1 expression and ACR in a rodent model of lung transplantation. STUDY DESIGN: Orthotopic left lung transplantation was performed from Lewis (donor) to Sprague-Dawley (recipient) rats, and ACR (Grade A0 to A4) was evaluated at days 3, 5, and 7. HO-1 expression was assessed by immunohistochemistry and Western analysis, and compared with the degree of ACR. Myeloperoxidase staining was evaluated as an indirect measure of oxidant stress. Donors and recipients were also treated with either an inhibitor of HO activity, tin protoporphyrin or an inducer, cobalt protoporphyrin, and the severity of ACR was compared with that in untreated allografts. RESULTS: HO-1 expression was elevated in transplanted versus native lungs or isografts, and the degree of elevation was closely correlated with ACR grade (p < 0.001). Similarly, myeloperoxidase expression increased with time and severity of ACR. Administration of the metalloporphyrins, tin protoporphyrin and cobalt protoporphyrin, produced no significant difference in the degree of ACR, but did alter the severity of ischemia-reperfusion injury. CONCLUSIONS: Similar to what occurs in human lung transplantation, HO-1 expression is increased in a rodent lung transplant model of ACR and correlates with the severity of rejection. Altering its expression does not appear to affect the degree of ACR.

Identification of stage I non-small cell lung cancer patients at high risk for local recurrence following sublobar resection.

OBJECTIVE: An increasing proportion of patients with stage I non-small cell lung cancer (NSCLC) is undergoing sublobar resection (L-). However, there is little information about the risks and correlates of local recurrence (LR) after such surgery, especially compared with patients undergoing lobectomy (L+). METHODS: Ninety-three and 318 consecutive patients with stage I NSCLC underwent L- and L+, respectively, from 2000 to 2006. Median follow-up was 34 months. RESULTS: In the L- group, the LR rates at 2, 3, and 5 years were 13%, 24%, and 40%, respectively. The risk of LR was significantly associated with tumor grade, tumor size, and T stage. The crude risk of LR was 33.8% (21 of 62) for patients whose tumors were grade ≥ 2. In the L+ group, the LR rates at 2, 3, and 5 years were 14%, 19%, and 24%, respectively. The risk of LR significantly increased with increasing tumor size, length of hospital stay, and the presence of diabetes. The L- group experienced a significant increase in failure in the bronchial stump/staple line compared with the L+ group (10% vs 3%; P = .04) and nonsignificant trends toward increased ipsilateral hilar and subcarinal failure rates. CONCLUSIONS: Patients with stage I NSCLC who undergo L- have an increased risk of LR compared with patients undergoing L+, particularly when they have tumors grade ≥ 2 or tumor size > 2 cm. If L- is considered, additional local therapy should be considered to reduce this risk of LR, especially with tumors grade ≥ 2 or size > 2 cm.