Reconstruction of esophageal stenosis that had persisted for 40 years using a free jejunal patch graft with virtual endoscopy assistance: A case report.

In this report, we present a case in which good results were achieved by treatment using a free jejunal patch graft with virtual endoscopy (VE) assistance in a patient whose swallowing had failed to improve for 40 years after he mistakenly swallowed sulfuric acid, despite pectoralis major myocutaneous flap grafting and frequent balloon dilatation surgery. During the last 20 years, virtual computed tomography imaging has improved remarkably and continues to be used to address new challenges. For reconstructive surgeons, the greatest advantage of VE is that it is a noninvasive modality capable of visualizing areas inaccessible to a flexible endoscope. Using VE findings, we were able to visualize the 3-dimensional shape beyond the stenosis. VE can also help predict the area of the defect after contracture release.

Adult T-cell leukemia/lymphoma with multiple integration of HTLV-1 provirus presenting as an isolated paranasal sinus tumor: a case report.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell lymphoma and etiologically associated with human T-lymphotropic virus type 1 (HTLV-1). Patients with ATLL commonly present with leukemic changes, systemic lymphadenopathy, and/or extranodal lesion and have very poor prognosis. METHODS AND RESULTS: We describe a rare case of ATLL presenting as an isolated paranasal mass. Southern blot analysis of the biopsied specimens demonstrated multiple integration bands of HTLV-1 provirus of different intensities. Chemotherapy resulted in complete resolution of the paranasal mass. Thereafter, the patient showed an indolent clinical course with leukemic changes and pulmonary and cutaneous ATLL lesions and remains alive more than 5 years from diagnosis. CONCLUSION: ATLL should be included in the differential diagnosis of sinonasal lymphoma, although the event is rare. Multiple HTLV-1 provirus integrations of different intensities may be indicative of good prognosis for ATLL.

Treatment and prognosis of squamous cell carcinoma of the external auditory canal and middle ear: a multi-institutional retrospective review of 87 patients.

PURPOSE: To examine the relative roles of surgery, radiotherapy, and chemotherapy in the management of patients with squamous cell carcinomas of the external auditory canal and middle ear. METHODS AND MATERIALS: The records of 87 patients with histologically confirmed squamous cell carcinoma who were treated between 1984 and 2005 were reviewed. Fifty-three patients (61%) were treated with surgery and radiotherapy (S + RT group) and the remaining 34 patients with radiotherapy alone (RT group). Chemotherapy was administered in 34 patients (39%). RESULTS: The 5-year actuarial overall and disease-free survival (DFS) rates for all patients were 55% and 54%, respectively. On univariate analysis, T stage (Stell's classification), treatment modality, and Karnofsky performance status had significant impact on DFS. On multivariate analysis, T stage and treatment modality were significant prognostic factors. Chemotherapy did not influence DFS. The 5-year DFS rate in T1, T2, and T3 patients was 83%, 45%, and 0 in the RT group (p < 0.0001) and 75%, 75%, and 46% in the S + RT group (p = 0.13), respectively. The 5-year DFS rate in patients with negative surgical margins, those with positive margins, and those with macroscopic residual disease was 83%, 55%, and 38%, respectively (p = 0.007). CONCLUSIONS: Radical radiotherapy is the treatment of choice for early-stage (T1) diseases, whereas surgery (negative surgical margins if possible) with radiotherapy is recommended as the standard care for advanced (T2-3) disease. Further clarification on the role of chemotherapy is necessary.

Life-style and environmental factors in the development of nasal NK/T-cell lymphoma: a case-control study in East Asia.

Cases of nasal NK/T-cell lymphoma (NKTCL) occur occasionally in Asian and Latin American countries but rarely in Western countries. The etiological role of life-style and environmental factors in nasal NKTCL was investigated. Five university hospitals in Japan and one each in Korea and China participated in this study; a total of 88 cases and 305 hospital controls were accrued during 2000-2005. The odds ratio (OR) of NKTCL obtained after adjustments of age, sex and country was 4.15 (95% confidence interval (CI), 1.74-9.87) for farmers, 2.81 (CI, 1.49-5.29) for producers of crops, 4.01 (CI, 1.99-8.09) for pesticide users, 11.65 (CI, 1.17-115.82) for residents near garbage burning plants, 2.95 (CI, 1.25-6.95) for former drinkers, and 0.49 (CI, 0.23-1.04) for current smokers. The ORs for crop producers, who minimized their exposure to pesticides by using gloves and glasses, and sprinkling downwind at the time of pesticide use, were 3.30 (95% CI, 1.28-8.54), 1.18 (95% CI, 0.11-12.13) and 2.20 (95% CI, 0.88-5.53), respectively, which were lower than those for producers who did not take these precautions. Exposure to pesticides and chemical solvents could be causative of NKTCL. Taken together, life-style and environmental factors might be risk factors for NKTCL.

NK-cell neoplasms in Japan.

Neoplasms putatively originating from precursor and mature natural killer (NK) cells are rare, and their clinical features are unclear. A nationwide survey was performed in Japan to clarify the clinical features of these neoplasms diagnosed between 1994 and 1998, and data for 237 patients who met the criteria for putative NK cell-lineage neoplasms were analyzed. Among them, 11 had myeloid/NK-cell precursor acute leukemia, 15 blastic NK-cell lymphoma, 21 precursor NK-cell acute lymphoblastic leukemia, 22 aggressive NK-cell leukemia/lymphoma, 149 nasal-type NK-cell lymphoma (123 nasal and 26 extranasal) and 19 chronic NK lymphocytosis. The median overall survival time of patients with aggressive NK-cell leukemia/lymphoma was 2 months, which for chronic NK lymphocytosis was more than 8 years, and that for the other types of NK-cell neoplasms was between 6 and 22 months. Nasal NK-cell lymphoma and extranasal NK-cell lymphoma share the same histology. The age of affliction was the same, but the sex was different with males predominantly having nasal NK-cell lymphoma and females extranasal NK-cell lymphoma. Patients with extranasal NK-cell lymphoma had the tendency to exhibit a more advanced state of disease, with significantly higher International Prognostic Index and LDH levels, and significantly lower hemoglobin and platelet levels. The overall survival, however, did not differ significantly. Precursor NK-cell acute lymphoblastic leukemia and blastic NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of blastic cells in the bone marrow or peripheral blood, but there were no significant differences for affected age, gender, involved sites or prognosis. Aggressive NK-cell leukemia/lymphoma and extranasal NK-cell lymphoma were arbitrarily defined by the presence or absence of 30% or more of large granular lymphocytes in the bone marrow or peripheral blood and it is possible that aggressive NK-cell leukemia/lymphoma is a leukemic phase of extranasal NK-cell lymphoma. The incidence of skin involvement, however, was significantly higher for extranasal NK-cell lymphoma, suggesting that the two diseases are different. In nasal NK-cell lymphoma, Epstein-Barr virus in tumor cells was detected in all patients tested, suggesting its causative role.

Expression of cell adhesion molecules and chemokine receptors: angioinvasiveness in nasal NK/T-cell lymphoma.

Sinonasal natural killer (NK)/T-cell lymphoma (NKTCL) is closely associated with Epstein-Barr virus (EBV) infection and expresses latent membrane protein (LMP)-1 and EB nuclear antigen (EBNA)-1, i.e., latency II of EBV infection. Angioinvasion by neoplastic cells is a characteristic feature of NKTCL, but its mechanism is unknown. To elucidate the molecular mechanism of angio-invasiveness in NKTCL, expression of cell adhesion molecules and chemokine receptors at mRNA and protein levels was examined using real-time PCR and immunohistochemistry in 17 NKTCL together with 10 diffuse large B-cell lymphoma (DLBL) and 9 non-neoplastic nasal mucosa as controls. EBV DNA was detected in 14 of 16 NKTCL examined, and 7 of these 14 expressed LMP-1. mRNA expression levels of integrin subunits alpha4, alpha L, alpha M, and beta2 were significantly higher in NKTCL than non-neoplastic controls. Integrin subunits alpha2 and alpha M were expressed at a significantly higher level in NKTCL with angioinvasion than those without. Expression level of alpha M was significantly higher in 7 cases of NKTCL with LMP-1 expression than 7 without. Immunohistochemistry showed expression of these molecules in NKTCL cells. These findings suggest that EBV infection might be involved in the pathogenesis of angioinvasion of NKTCL through up-regulation of alpha M by LMP-1.

p53, K-ras, c-kit and beta-catenin gene mutations in sinonasal NK/T-cell lymphoma in Korea and Japan.

Mutations of p53, K-ras, c-kit, and beta-catenin gene were examined in 100 cases of sinonasal NK/T-cell lymphoma (NKTCL) from Korea and Japan. Age of patients ranged from 12 to 72 (median 41.0) in Korea and 27 to 82 (median 61.0) years in Japan. Gene mutations were analyzed on paraffin-embedded specimens by PCR-SSCP followed by direct sequencing. p53 is a well-known tumor suppressor gene. c-kit gene encodes a receptor tyrosine kinase, which plays a crucial role in proliferation and differentiation of hematopoietic stem cells. Mutations of K-ras and beta-catenin are frequently observed in cancers. Thirteen of 42 (31.0%) cases from Korea and 36 of 58 (62.1%) from Japan had p53 mutations, showing significant differences in the incidence of p53 mutation between two countries. Of the Japanese cases 18 (31.0%) had mutations in exon 4, while only 3 cases (7.1%) were found in Korea cases (p<0.01 by chi2 test). K-ras, c-kit and beta-catenin mutations were also found in higher incidence in Japanese cases. In conclusion, different frequency of p53 mutations with different pattern of exon involvement and difference in age of disease onset is evident between sinonasal NKTCL in Korea and Japan.

Frequent mutations of Fas gene in nasal NK/T cell lymphoma.

Fas (Apo-1/CD95) is a cell-surface receptor involved in cell death signaling through binding of Fas ligand. Mutation of Fas gene in lymphoid cells results in accumulation of these cells, which might thus contribute to lymphomagenesis. We examined the open reading frame of Fas cDNA in 14 cases of nasal NK/T-cell lymphoma. Mutations of Fas gene were detected in seven (50%) of 14 cases which comprised four frameshift, two missense, and one silent mutations. Frameshift mutations were caused by insertion of 1 bp (A) at nucleotide 1095 in two cases and by deletion of 1 bp at nucleotide 597 and at 704, respectively, in one each. Mouse T-cell lymphoma cells transfected with two missense mutated genes and frameshift mutations caused by insertion of 1 bp (A) at nucleotide 1095 were resistant to apoptosis induced by the anti-Fas antibody. These findings suggested that accumulation of lymphoid cells with Fas mutations provides a basis for the development of nasal NK/T-cell lymphoma.