Takeshi Mimura

Difference in Prognostic Significance of Maximum Standardized Uptake Value on [18F]-Fluoro-2-Deoxyglucose Positron Emission Tomography Between Adenocarcinoma and Squamous Cell Carcinoma of the Lung

OBJECTIVE This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. METHODS We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n = 132) or squamous cell carcinoma (n = 44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. RESULTS The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P< 0.001). Analyses of receiver operating characteristic curves identified an optimal maximum standardized uptake value cutoff value to predict recurrence of 3.7 for adenocarcinoma, whereas such an indicator could not be identified for squamous cell carcinoma. Although 2-year disease-free survival rates were 70.2% for maximum standardized uptake value ≤6.95 and 59.3% for maximum standardized uptake value >6.95 (P = 0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P < 0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P < 0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P = 0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P = 0.001). CONCLUSIONS Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung.

Novel marker D2-40, combined with calretinin, CEA, and TTF-1: an optimal set of immunodiagnostic markers for pleural mesothelioma.

Malignant pleural mesothelioma is a challenging disease with regard to diagnosis and treatment; early and accurate diagnosis would lead to appropriate therapeutic strategies, including extrapleural pneumonectomy. Immunohistochemistry has proven valuable for the diagnosis of the most common epithelioid mesothelioma, although it is often difficult to differentiate it from pulmonary or metastatic adenocarcinoma with absolute certainty if a single antibody is employed. The current study was designed to identify an immunodiagnostic panel for pleural mesothelioma.

Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a cause of efficient adhesion and growth on mesothelium

Cell adhesion molecule 1 (CADM1), formerly referred to as SgIGSF, TSLC1, or Necl-2, has been characterized as a mast-cell adhesion molecule that mediates efficient interactions with mesothelial cells. Here, we examined whether CADM1 might be involved in the diffuse tumor growth over the pleural surface that characterizes malignant pleural mesothelioma (MPM). Immunohistochemical and western blot analyses revealed that 14 (25%) of 57 MPMs expressed the full-length form of CADM1 on the cell membrane, but non-neoplastic mesothelial cells did not express it at all. The majority of available MPM cell lines also expressed the full-length form of CADM1. We compared CADM1-positive and -negative MPM cells in culture within soft agar and in coculture on mesothelial or fibroblastic monolayers. Within soft agar, CADM1-negative MPM cells were capable of forming colonies, whereas CADM1-positive cells were not, suggesting that CADM1 is a potential tumor suppressor of MPM, consistent with the past characterization of this molecule in other types of tumors. However, in coculture on mesothelial cell monolayers lacking full-length CADM1, CADM1-positive MPM cells spread more widely and grew more quickly, whereas the CADM1-negative cells piled up. Transfection of the CADM1-negative cells with CADM1 cDNA caused them to behave like the CADM1-positive cells, with faster, more widespread growth. These phenotypic differences were not detectable in cocultures on lung fibroblastic monolayers, in which all MPM cells grew much more slowly than on mesothelial cells, irrespective of CADM1 positivity. CADM1 thus appears to mediate efficient adhesion and growth of MPM cells specifically on mesothelial cells, probably via trans-heterophilic binding, and thus may be involved in the manifestation of a considerable subset of MPMs as diffusely growing tumors disseminated over the pleural surface.

Negative prognostic influence of micropapillary pattern in stage IA lung adenocarcinoma

OBJECTIVES There is uncertainty as to which factors determine the aggressiveness of lung adenocarcinoma with a micropapillary pattern (MPP). The present study aimed to clarify the influence of a MPP on the malignant aggressiveness of clinical stage IA lung adenocarcinoma. METHODS We retrospectively examined 347 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection. We defined MPP-positive as accounting for ≥5% of the entire tumour. RESULTS Forty-eight (14%) and 299 (86%) patients were MPP-positive and negative, respectively. Lymphatic (P = 0.003) and vessel (P = 0.029) invasion as well as lymph node metastasis (P = 0.002) were more frequent in the MPP-positive than negative group. Five-year disease-free survival (DFS) rates were significantly lower in the MPP-positive than negative group (69.7 vs 89.3%, P < 0.001). Multivariate analysis for DFS showed that MPP (P = 0.048), lymphatic invasion (P = 0.003) and vessel invasion (P = 0.002) were independent poor prognostic factors. In addition, higher proportions (<5%, 5-30% and ≥30%) of MPP were associated with a poorer prognosis (89.3, 76.0, and 48.1%, respectively; P < 0.001). The prognosis of patients with MPP-positive tumours and negative tumours harbouring lepidic and solid predominant growth patents did not differ (100 vs 96.8%, P = 0.564; 66.7 vs 62.5%, P = 0.791, respectively). On the other hand, the prognosis tended to be poorer for patients with papillary predominant MPP-positive tumours than for those with negative tumours (62.5 vs 82.5%, P = 0.075). CONCLUSIONS MPP has an effect on tumour malignancy and patients with tumours harbouring a higher ratio of MPP or papillary predominant subtypes have worse survival.

Surgical treatment of clinical N1 non-small cell lung cancer: Ongoing controversy over diagnosis and prognosis

PurposeThe preoperative assessment of nodal status in lung cancer is complicated and problematic for physicians and surgeons. Although many patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) are candidates for surgical treatment, these patients represent a heterogeneous subgroup with unpredictable survival. We conducted this study to evaluate the surgical results of cN1 disease and to attempt to clarify the delicate issues surrounding its diagnosis and prognosis.MethodsThe subjects of this study were 187 consecutive patients with cN1 adenocarcinoma or squamous cell carcinoma of the lung, who underwent complete resection without induction therapy.ResultsOnly 25% of the adenocarcinomas and 54% of the squamous cell carcinomas were correctly diagnosed as N1 disease preoperatively. Multiple logistic regression analyses revealed that adenocarcinoma (P = 0.0141) was a significant predictor of pN2. Multivariate analyses revealed that nodal metastasis (P < 0.0001), large tumor size (P = 0.0079), and high serum carcinoembryonic antigen value (P = 0.0096) were significantly poor prognostic factors in cN1 patients.ConclusionsIt is difficult to diagnose nodal status in patients with cN1 disease, which requires various surgical procedures, including plasty, possibly with adjuvant therapy in a defined high-risk subgroup.

Outcomes after lobar versus sublobar resection for clinical stage I non−small cell lung cancer in patients with interstitial lung disease

Objective: Since the prognosis after standard lobectomy for non−small cell lung cancer (NSCLC) in patients with interstitial lung disease (ILD) is poor, we investigated the possibility of sublobar resection for the improvement of the surgical results in such patients. Methods: Of 796 consecutive patients with clinical stage I NSCLC who underwent pulmonary resection, 107 were diagnosed with ILD using high‐resolution computed tomography (HRCT). Overall survivals (OS) were compared between patients with non‐ILD and those with ILD or between patients with ILD who underwent lobectomy and those who underwent sublobar resection. ILD patterns consisted of usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. The log‐rank statistics and Cox proportional hazard models were used to test for survival differences. Results: OS was significantly lower in patients with “ILD inconsistent with UIP” pattern (hazard ratio [HR], 2.66; 95% confidence interval [CI], 1.19‐5.97; P = .014), or “ILD with possible UIP or UIP” patterns (HR, 2.38; 95% CI, 1.76‐3.21; P < .001) compared with patients with non‐ILD. No significant difference in OS was observed between patients with ILD who underwent either lobectomy or sublobar resection (HR, 1.82; 95% CI, 0.81‐4.06; P = .19). Multivariable Cox analysis demonstrated diffusing capacity of the lung for carbon monoxide (HR, 0.95; 95% CI, 0.91‐0.99; P = .009) and not surgical procedure (HR, 2.76; 95% CI, 0.83‐9.16; P = .099), as an independent prognostic factor for OS. Conclusions: Sublobar resection may be a potential alternative choice for clinical stage I NSCLC with ILD on HRCT.

What are the radiologic findings predictive of indolent lung adenocarcinoma

OBJECTIVE Small pulmonary nodules are often followed up. This study aimed to establish radiographic criteria with which to accurately and reproducibly predict indolent cancers including adenocarcinoma in situ. METHODS We examined correlations between pre-operative factors and surgical outcomes, including pathological findings and prognosis among 609 patients with clinical Stage IA lung adenocarcinoma that had been completely resected at multiple institutions. Indolent cancers were defined as tumors without lymphatic, blood vessel, pleural invasion or lymph node involvement (LY0V0PL0N0) regardless of stromal invasion. RESULTS Pathological assessments of specimens of 35 of 85 (41%) pure ground glass opacity tumors including 3 (23%) of 13 pure ground glass opacity tumors ≤ 1 cm, revealed partially invasive components. Receiver operating characteristic curves for LY0V0PL0N0 revealed solid tumor size ≤ 6 mm on high-resolution computed tomography or maximum standardized uptake values ≤ 0.6 on 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as radiographic indolent tumor criteria for predicting indolent tumors. Among 216 (35.5%) of 609 patients who met these criteria, none developed recurrence over a median follow-up of 41.6 months. CONCLUSIONS Pure ground glass opacity lesions on high-resolution computed tomography could pathologically include invasive components and would not correspond to adenocarcinoma in situ. Solid tumor size on high-resolution computed tomography and maximum standardized uptake values on positron emission tomography/computed tomography can predict indolent LY0V0PL0N0 lung tumors that can be followed up.

Infrainguinal Bypass Surgery for Chronic Arterial Occlusive Disease Associated with Essential Thrombocythemia: Report of a Case

A 63-year-old man was referred to our hospital with a 3-year history of intermittent claudication, and his angiogram showed a total occlusion of the bilateral infrainguinal arteries. In addition, based on a platelet count of 172 × 104/mm3 as well as the characteristic bone marrow findings, he was diagnosed to have essential thrombocythemia. After the platelet count and aggregation response improved on administration of ranimustine and antiplatelet agents, infrainguinal bypass surgery was performed using the saphenous vein and prosthetic grafts. The bilateral grafts had been patent for 10 months postoperatively, but his discontinuance of medication caused an acute occlusion of the prosthetic graft. The graft was salvaged with a prompt thrombectomy and, now under strict medication control, he is leading an active life.

Radiologic findings to predict low-grade malignant tumour among clinical T1bN0 lung adenocarcinomas: lessons from histological subtypes

OBJECTIVE Some clinical T1bN0 (cT1bN0) lung adenocarcinomas (2-3 cm) are thought to have less-aggressive and less-malignant behaviour although most cT1aN0 tumours (≤2 cm) are indolent. The present study aimed to identify pre-operative radiographic findings that can predict cT1bN0 lung adenocarcinoma with low-malignant aggressiveness in consideration of histological subtypes. METHODS The clinicopathological features and prognoses of 224 consecutive patients (histological subtype set, n = 122; prognosis set, n = 224) with cT1bN0 lung adenocarcinoma were retrospectively examined. Adenocarcinoma in situ, minimally invasive adenocarcinoma, lepidic, node-negative papillary and node-negative acinar predominant invasive adenocarcinomas were defined as low-grade malignant, whereas solid, micropapillary, node-positive acinar and node-positive papillary predominant invasive adenocarcinoma were defined as high-grade malignant. RESULTS Receiver operating characteristics analysis revealed that the criteria of solid tumour size ≤1.8 cm on high-resolution computed tomography and the maximum standardized uptake value ≤3.2 on positron emission tomography/computed tomography could predict low-grade malignant tumour in the histological subtype set. Among 95 (42.4%) of 224 patients who met the criteria for the prognosis set, 94 (98.9%) had no lymph node metastasis and 93 (97.9%) had no recurrence (median follow-up, 43.6 months). The 3 year recurrence-free survival rates were 94.9 and 79.0% in patients whose pre-operative findings met and did not meet the criteria, respectively. CONCLUSIONS Pre-operative radiographic findings of solid tumour size and the maximum standardized uptake value could identify low-grade malignant tumour among cT1bN0 lung adenocarcinomas, which account for about half of all cT1bN0 tumours. Patients with pre-operative lung tumour findings that fulfill the criteria could be candidates for sublobar resection.

Impact of Lepidic Component Occupancy on Effects of Adjuvant Chemotherapy for Lung Adenocarcinoma.

BACKGROUND The prognosis of lepidic predominant lung adenocarcinoma is favorable. We postulated that lepidic predominant tumors might not require postoperative adjuvant chemotherapy. The present study aims to determine whether lepidic component occupancy affects overall survival after postoperative adjuvant chemotherapy for lung adenocarcinoma. METHODS Clinical and pathologic data were collected from a database and from the medical records of 964 patients with completely resected lung adenocarcinoma. We assessed the influence of lepidic component occupancy in the tumor on the outcomes of adjuvant chemotherapy. RESULTS Among the patients, 270 received adjuvant chemotherapy and 694 did not, and 415 and 549 had lepidic predominant and non-lepidic predominant tumors, respectively. Adjuvant chemotherapy contributed to better overall survival compared with observation in non-lepidic predominant tumors (p = 0.025). Multivariate analyses revealed age, sex, stage, lepidic component occupancy, and adjuvant chemotherapy as independent prognostic factors for overall survival. The overall survival was significantly longer for patients with non-lepidic predominant tumors at stages IA, IB, and II-III under adjuvant chemotherapy compared with observation (p = 0.040, p = 0.007, and p = 0.012, respectively), whereas survival rates were similar for patients with all stages of lepidic predominant tumors even after propensity score matching study. CONCLUSIONS Lepidic component occupancy reflected the effect of adjuvant chemotherapy for lung adenocarcinoma. Adjuvant chemotherapy did not have much impact for lepidic predominant tumors and could be considered for non-lepidic predominant tumors even at stage IA.