Takuya Onuki

Possible Delayed Cut-End Recurrence After Limited Resection for Ground-Glass Opacity Adenocarcinoma, Intraoperatively Diagnosed as Noguchi Type B, in Three Patients

Introduction: In our limited resection trial of pulmonary peripheral ground-glass opacity (GGO) lesions from 1998 to 2002, limited resection of Noguchi type A and B carcinomas seemed to have a positive outcome. However, recently three of the 24 patients, with mixed GGO lesions intraoperatively diagnosed as type B, developed a solid lesion at the cut-end scar. Methods: Medical records and radiology and pathology findings of the three patients were reviewed. We also analyzed epidermal growth factor receptor gene mutations when possible. Results: Radiologically, these three second tumors were clearly cut-end scar area recurrences. However, other pathologic and mutation findings suggest metachronous primary cancers developed in Case 1, cut-end recurrence in Case 2, and needle biopsy implantation in Case 3. It is difficult to definitively conclude whether the second tumors were recurrences or metachronous primaries. Conclusions: These second tumors have convinced us that our initial caution in concluding GGO lesions can be cured by limited resection was very appropriate. The recurrences definitely indicate that continuing follow-up attention for more than 5 years is needed after limited resection even for GGO bronchioloalveolar carcinomas.

Pathologic Radioresponse of Preoperatively Irradiated Invasive Thymomas

Background: We have been applying preoperative radiotherapy (RT) to Masaoka stage III thymomas intending to make surgical resection more complete by reducing mass volume, to prevent possible dissemination caused by surgical manipulation and to get better survival as a result. However, the radioresponses vary from tumor to tumor. We hypothesized that thymoma is a variable radioresponsive tumor depending on pretreatment histology. Materials and Methods: Twenty-one of stage III thymomas underwent preoperative RT plus surgery followed by postoperative RT between 1982 and 2004. Reduction ratios, histopathologic changes according to WHO histologic criteria, resectability, long-term survival, and disease control, by preoperative RT were analyzed. Results: Pretreatment WHO subtypes were type AB (n = 1), B1 (5), B2 (6), B3 (4), and unclassified (5). Sixteen tumors (76.2%) decreased in size after preoperative RT with a mean (median) reduction ratio of 30.8% (27.0%). Type B1or B2 group had higher reduction ratio than type B3 group (mean value of 39.7%, 31.8%, and 21.0%, respectively, p < 0.01). Histopathologically, lymphocyte diminished markedly in type B1 thymoma, and both lymphocyte and epithelial cells diminished in type B2, whereas none of the B3 tumors showed any histologic change. The values of all the cases is 90.5% in complete resection, 19.0% in no combined resection of the adjacent organs, and 77.6% and 83.6% in overall and disease-free 10-year survival, respectively, and these value do not differ according to the WHO histologic criteria. Conclusions: This modality at modest doses was macroscopically and histopathologically effective on tumors particularly in WHO B1 and B2 thymomas than WHO B3 thymoma. The therapeutic benefit of preoperative RT followed by surgery and postoperative RT for stage III thymomas should be defined thoroughly.

Limited thymectomy for stage I or II thymomas

BACKGROUND Once an anterior mediastinal tumor has been diagnosed as a thymoma, complete excision including the thymic gland and perithymic fat is currently the procedure of choice. However, little is known about the clinical outcome of grossly encapsulated thymomas excised only with the surrounding tissue while leaving a part of the thymic gland. METHODS A retrospective historical comparative study was conducted on 79 patients who had received surgery for stage I (n=25) or stage II (n=54) thymomas. Total thymectomy was performed in 61 patients (Total Thymectomy Group), whereas resection of tumors with only the surrounding tissue was carried out in 18 (Limited Thymectomy Group). The follow-up interval was longer in the Limited Thymectomy Group because these patients were treated longer ago (104.2+/-58.1 months vs 67.3+/-54.8 months, p<0.05). RESULTS One case in the Limited Thymectomy Group showed postoperative myasthenia gravis (5.6%). Two patients with multiple thymomas (2.5%) were treated with total thymectomy. One case in the Limited Thymectomy Group, which had been diagnosed as Masaoka stage II and WHO type B3 at initial surgery, recurred. None died of tumor progression in this study. Disease free survival rates at 10 years did not differ between the Limited Thymectomy and Total Thymectomy Groups (85.7% and 82.0%, respectively). There were no statistical differences in the incidence of postoperative myasthenia gravis and disease free survival between the two groups. CONCLUSION Resection of thymomas with surrounding tissue instead of total thymectomy can be indicated for stage I or II thymomas in light of disease free and overall survival, post-operative onset of MG, and the incidence of multiple lesions.

OCIA domain containing 2 is highly expressed in adenocarcinoma mixed subtype with bronchioloalveolar carcinoma component and is associated with better prognosis

Although lung adenocarcinoma is a major cause of cancer death worldwide, details of its molecular carcinogenesis and stepwise progression are still unclear. To characterize the sequential progression from bronchioloalveolar adenocarcinoma of the lung (BAC, in situ carcinoma) to adenocarcinoma mixed subtype with BAC component, polymerase chain reaction‐based cDNA suppression subtractive hybridization (SSH) was carried out using two representative cases of BAC (non‐invasive tumors) and adenocarcinoma mixed subtype with BAC (invasive tumors). Through differential screening, virtual reverse northern hybridization and quantitative real‐time reverse‐transcription–polymerase chain reaction (qRT‐PCR) we selected five genes (TncRNA, OCIAD2, ANXA2, TMED4 and LGALS4) that were expressed at significantly higher levels in invasive adenocarcinoma mixed subtype with BAC than in BAC. After in situ hybridization and qRT‐PCR analyses, we confirmed that only the OCIAD2 gene showed significantly higher expression in the tumor cells of invasive adenocarcinoma mixed subtype with BAC than in BAC (P = 0.026). We then carried out in situ hybridization of OCIAD2 in 56 adenocarcinoma mixed subtype with BAC component and assessed the correlation between OCIAD2 expression and clinicopathological features. In contrast to our expectation, the patients with OCIAD2 expression showed a better clinical outcome than those without OCIAD2 expression, and OCIAD2 expression showed an inverse correlation with lymphatic invasion, blood vessel invasion and lymph node metastasis. These results suggest that OCIAD2 begins to express at the progression from in situ to invasive carcinoma, and is associated with the favorable prognosis of adenocarcinoma mixed subtype with BAC component. (Cancer Sci 2007; 98: 50–57)

Radiologically Indeterminate Pulmonary Cysts in Birt-Hogg-Dubé Syndrome

Birt-Hogg-Dubé (BHD) syndrome is an inherited disease characterized by recurrent pneumothorax. We report some unusual clinicopathologic features of the lung in a Japanese family with this syndrome presenting with recurrent pneumothorax. Radiologic imaging did not show detectable lesions; however, at video-assisted thoracic surgery (VATS), multiple diffusely distributed microcysts were visible on the pleura. This characteristic morphologic feature was common to all affected family members. The proband underwent genetic testing and BHD syndrome was diagnosed. Although many patients with BHD syndrome with pneumothorax show obvious pulmonary cysts, this case suggests that radiologically indeterminate cysts have the potential to cause pneumothorax.

Mediastinitis of bronchogenic cyst caused by endobronchial ultrasound‐guided transbronchial needle aspiration

Here, we describe the case of a 56‐year‐old female patient who was diagnosed with an anterior mediastinal cyst measuring 26 × 16 mm in size. An endobronchial ultrasound‐guided transbronchial needle aspiration was performed, and punctures occurred three times. The patient was then prescribed cefditoren pivoxil. Three days after the procedure, the patient developed infective mediastinitis. Panipenem/betamipron, clindamycin, and human immunoglobulin were administered, and her symptoms improved over 2 weeks. Five months after developing mediastinitis, surgical resection of the cyst was performed with inverted L‐shaped mini‐sternotomy. The cystic lesion strongly adhered to the surrounding tissues. The final pathological diagnosis was a bronchogenic cyst. Endobronchial ultrasound‐guided transbronchial needle aspiration is not a completely sterile procedure and can lead to severe infective complications in the mediastinum. Although this procedure may not be contraindication for use with mediastinal cystic lesions, physicians must take into account the risk of severe infective complications.

Early-stage thymic carcinoma: is adjuvant therapy required?

Although the prognosis of advanced thymic carconoma remains poor, previous reports have shown survival rates of 70% to 100% in patients with Masaoka stage I or stage II of the disease who were treated with surgery followed by adjuvant therapy. However, the role of adjuvant therapy in these stages is controversial. We retrospectively evaluated the outcome of 4 patients with Masaoka stage II thymic carcinoma who were treated with surgery alone between 1992 and 2008. No patient had stage I of the disease. Primary tumors were preoperatively evaluated by chest X-ray and computed tomography. Needle biopsy was not performed because the tumors were clinically diagnosed as noninvasive thymomas. The largest diameter of the primary tumor was 65 mm. Mediastinal lymphadenopathy was not detected by computed tomography. All patients underwent transsternal thymectomy. Mediastinal lymph node dissection was not performed. None of the patients received adjuvant chemotherapy and/or irradiation. Histopathologic examination revealed squamous cell carcinoma in 3 patients and undifferentiated carcinoma in one. Pathologic invasion to the adjacent organs or lymph node metastasis was not detected. All patients were alive and free from relapse at a follow-up of 72 months (range, 12-167 months). Radical resection without adjuvant therapy could be a treatment option for early Masaoka stage thymic carcinoma with low-grade histology.

Invasive thymoma with pure red cell aplasia and amegakaryocytic thrombocytopenia

We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL), thrombocytopenia (platelet count, 0.6 × 104/μL), and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT). On Day 8 of admission, the patient received immunosuppressive therapy together with cyclosporine for the 2 severe hematologic diseases, which were stabilized within 2 months. Subsequently, total thymectomy was performed. The diagnosis of the tumor invading the left lung was invasive thymoma, Masaokakoga stage III. The histological diagnosis was World Health Organization type AB. Thymoma accompanied with PRCA and AAMT is very rare, and, based on our case, immunotherapeutic therapy for the hematologic disorders should precede surgical intervention.

Primary and Secondary Spontaneous Pneumothorax: Prevalence, Clinical Features, and In-Hospital Mortality

Background. Optimal treatment practices and factors associated with in-hospital mortality in spontaneous pneumothorax (SP) are not fully understood. We evaluated prevalence, clinical characteristics, and in-hospital mortality among Japanese patients with primary or secondary SP (PSP/SSP). Methods. We retrospectively reviewed and stratified 938 instances of pneumothorax in 751 consecutive patients diagnosed with SP into the PSP and SSP groups. Factors associated with in-hospital mortality in SSP were identified by multiple logistic regression analysis. Results. In the SSP group (n = 327; 34.9%), patient age, requirement for emergency transport, and length of stay were greater (all, p < 0.001), while the prevalence of smoking (p = 0.023) and number of surgical interventions (p < 0.001) were lower compared to those in the PSP group (n = 611; 65.1%). Among the 16 in-hospital deceased patients, 12 (75.0%) received emergency transportation and 10 (62.5%) exhibited performance status (PS) of 3-4. In the SSP group, emergency transportation was an independent factor for in-hospital mortality (odds ratio 16.37; 95% confidence interval, 4.85–55.20; p < 0.001). Conclusions. The prevalence and clinical characteristics of PSP and SSP differ considerably. Patients with SSP receiving emergency transportation should receive careful attention.

Thymectomy during Myasthenic Crisis under Artificial Respiration

A 34-year-old man was diagnosed with thymoma, which was evaluated preoperatively as stage II or III, with myasthenia gravis (MG). The size of the tumor was 70 × 44 × 80 mm. No invasion to neighboring organs was observed. Prednisolone was prescribed for stabilization of MG. However, a myasthenic crisis (MC) occurred, and intensive care, including emergent endobronchial intubation followed by artificial ventilation, pulse steroid therapy, high-dose intravenous immunoglobulin, and tacrolimus hydrate, was initiated. A chest computed tomography on day 6 revealed tumor reduction to 50 × 30 × 60 mm. An extended total thymectomy by median sternotomy was performed, and artificial ventilation was continued after that. Scheduled artificial ventilation and steroid therapy together can, therefore, enable complete resection of thymoma in patients undergoing treatment for MC. While ventilation helps avert a respiratory failure, the steroid therapy temporarily reduces the tumor size, making resection easier.