World Health Organization Histological Typing Research Articles

Histologic Diversity of Thymic Epithelial Tumors in Patients with Myasthenia Gravis

Background and Objective:Thymic epithelial tumors (TETs) include thymic carcinomas and thymomas, the latter of which can be further categorized by the World Health Organization (WHO) histologic classification based on the morphology of epithelial cells and the ratio of lymphocyte to epithelial cells. TETs are rare malignancies with an incidence of 0.15 per 100,000 in the United States. While their etiologies remain unknown, these tumors are associated with distinctly high rates of autoimmune disorders and paraneoplastic syndromes. Approximately 30% of patients with thymoma also carry a diagnosis of myasthenia gravis (MG). For the present retrospective study, we created a database of patients with TETs and examined prevalence of each histologic subtype in patients with MG.
 Methods:Drs. Patrick Loehrer, Kenneth Kesler, and colleagues have collaborated at the Indiana University Simon Comprehensive Cancer Center to care for over 1000 patients with TETs. The electronic health records of these patients were accessed via Cerner and used to input demographic, diagnostic, and histologic data into a REDCap database. These tumors were further categorized by WHO classification, and those comprising multiple histologic types were included separately in each subgroup.
 Results:Of 626 patients deemed to have sufficient documented histologic and diagnostic data, 110 had both MG and a TET diagnosis confirmed by pathology report. The greatest prevalence of WHO histologic type in patients with thymoma and MG was Type B2 (47), followed by Type B3 (34), Type B1 (22), Type A (9), Type AB (7), and unspecified thymoma (7). Notably, only 3 of 159 (1.87%) total patients with thymic carcinoma had comorbid MG in contrast to 107 of 467 (22.91%) patients with thymoma and MG; this suggests a uniquely favorable microenvironment of thymoma in patients with MG.
 Clinical Impact and Implications:Future work will aim to determine whether histologic classification has a predictive value for tumor prognosis in patients with and without MG. Furthermore, patterns of gene expression associated with thymoma in patients with and without MG may elucidate the etiologic mechanisms for the development of this autoimmune disorder.

The Clinical Significance of Preoperative 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Predicting Distant Recurrence in Thymoma

AimsThymomas sometimes require treatment for various recurrence patterns, despite their relatively good survival rates after resection. We focused on their maximum standardised uptake value (SUVmax) on preoperative 18F-fluorodeoxyglucose positron emission tomography as a tumour recurrence predictor in completely resected thymomas. Those with a high SUVmax might be at an increased recurrence risk, irrespective of tumour size. We categorised cases into axes (tumour size and SUVmax) and determined whether cluster analysis predicts recurrence patterns and freedom from recurrence (FFR). Materials and methodsOf the 115 patients who underwent primary surgery for thymoma between 2005 and 2018, 66 were evaluated. According to the Masaoka stage and World Health Organization (WHO) histological type, all histological diagnoses were obtained after resection. All recurrences were diagnosed using computed tomography and categorised into three patterns: distant, local and regional recurrences. A multiple regression analysis was carried out to identify predictors for each recurrence pattern. Cluster analysis was carried out based on tumour size and SUVmax. The FFR rate was evaluated. ResultsAll patients with preoperative SUVmax <3.4 were free from recurrence regardless of Masaoka stage, WHO histological classification and tumour size. Multiple regression analysis revealed that the SUVmax was the only significant predictor for distant recurrence. All cases were divided into three clusters. Cluster 3, with average tumour size and a high SUVmax, showed a higher risk of distant recurrence rate (60%) and a significantly lower FFR rate (P = 0.003). ConclusionsThe preoperative positron emission tomography/computed tomography SUVmax could be a useful thymoma recurrence predictor, especially for distant recurrences. In addition, cluster analysis revealed that cases with average tumour sizes and extremely high SUVmax were identified to have a higher recurrence risk and a significantly lower FFR rate than those in other clusters. Even after complete resection, such cases should be closely followed-up and screened for distant recurrence.

Usefulness of positron-emission tomography for predicting the World Health Organization grade of thymic epithelial tumors.

BackgroundIt is often difficult to distinguish between thymoma and thymic carcinoma by preoperative radiological tests. While there have been some reports that the maximum standardized uptake value (SUVmax) in positron emission tomography‐computed tomography (PET‐CT) is useful to this end, no large‐scale analysis has been performed. We therefore analyzed the usefulness of the SUVmax and tumor size (TS) for differentiating thymic epithelial tumors.MethodsFrom 2011 to 2019, 129 patients with thymic epithelial tumor who underwent PET‐CT before surgical treatment were enrolled. The relevance of the SUVmax to the World Health Organization (WHO) histological type was assessed. To reduce the impact of the TS, the ratio of the SUVmax to the TS was also investigated.ResultsA total of 99 thymoma cases and 30 thymic carcinoma cases were enrolled into the study. The SUVmax and SUVmax/TS of thymic carcinoma were significantly higher than those of thymoma (SUVmax: 7.7 ± 3.4 vs. 3.3 ± 1.3, p < 0.01; SUVmax/TS: 1.5 ± 0.7 vs. 0.6 ± 0.4, p < 0.01). Focusing on the patients with a moderate SUVmax of ≤5 (84 thymoma and 4 thymic carcinoma), the SUVmax/TS values of thymic carcinoma were still significantly higher than those of thymoma (1.6 ± 0.8 vs. 0.6 ± 0.4, p < 0.01).ConclusionsPET‐CT might provide significant information for differentiating images of thymoma and thymic carcinoma. We experienced several cases of thymic carcinoma with a moderate SUVmax of ≤5, and SUVmax/TS was considered a useful parameter for differentiating such cases.

Prognostic Value of Preoperative Serum Carcinoembryonic Antigen for Overall Survival and Recurrence-Free Survival in Resectable Thymic Epithelial Tumors.

Introduction: Tumor markers have been shown to be closely related to the long-term survival of patients with cancer and the recurrence of various malignant tumors. However, their role in thymic epithelial tumors (TETs) remains to be elucidated. We aimed to investigate whether the preoperative tumor biomarkers carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) could serve as independent predictors of postoperative prognosis in patients with TETs. Materials and Methods: We retrospectively included a total of 111 patients with TETs who underwent thymectomy at our hospital. Cox regression analysis was used to evaluate the statistical significance of CEA and NSE as independent predictors of overall survival (OS) and recurrence-free survival (RFS). Kaplan–Meier curves were used to present the results of our survival analyses. Results: Cox regression analysis showed that T stage, World Health Organization (WHO) histologic type, tumor size, and CEA levels served as independent prognostic factors for OS (P < .05). Whereas for RFS, multivariate analysis showed that only T stage, WHO histologic type, and drinking history were independently associated with it (P < .05). Conclusion: Our study found that preoperative serum CEA levels and tumor size may be strong predictors of postoperative OS in patients with TETs.

Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type.

Further characterization of thymic epithelial tumors (TETs) is needed. Genomic information from 102 evaluable TETs from The Cancer Genome Atlas (TCGA) dataset and from the IU-TAB-1 cell line (type AB thymoma) underwent clustering analysis to identify molecular subtypes of TETs. Six novel molecular subtypes (TH1-TH6) of TETs from the TCGA were identified, and there was no association with WHO histologic subtype. The IU-TAB-1 cell line clustered into the TH4 molecular subtype and in vitro testing of candidate therapeutics was performed. The IU-TAB-1 cell line was noted to be resistant to everolimus (mTORC1 inhibitor) and sensitive to nelfinavir (AKT1 inhibitor) across the endpoints measured. Sensitivity to nelfinavir was due to the IU-TAB-1 cell line’s gain-of function (GOF) mutation in PIK3CA and amplification of genes observed from array comparative genomic hybridization (aCGH), including AURKA, ERBB2, KIT, PDGFRA and PDGFB, that are known upregulate AKT, while resistance to everolimus was primarily driven by upregulation of downstream signaling of KIT, PDGFRA and PDGFB in the presence of mTORC1 inhibition. We present a novel molecular classification of TETs independent of WHO histologic subtype, which may be used for preclinical validation studies of potential candidate therapeutics of interest for this rare disease.

Calcification in thymomas can predict invasiveness to surrounding organs

BackgroundThymomas are the most common type of anterior mediastinal tumors. Calcification is sometimes observed in thymomas using computed tomography (CT), and it is more frequent in invasive thymomas than in noninvasive thymomas. However, the significance of calcification in thymomas remains unknown. This study aimed to evaluate the significance of calcification in thymomas on invasiveness to surrounding organs and investigate the characteristics of thymoma cases with calcification at our institution.MethodsWe included thymoma patients treated at our institution between 2000 and 2016, and evaluated their characteristics, including demographics, calcification on CT, histology, Masaoka stage, and myasthenia gravis status. The patients were categorized into calcification (C) and noncalcification (NC) groups.ResultsAmong 51 included patients, 11 (21.6%) had calcification. A higher proportion of group C patients had World Health Organization histological type B2 and B3 tumors (high‐risk) than type A, AB, and B1 tumors (low‐risk; p = 0.0477). The number of patients with Masaoka stages III and IV were significantly higher in the C group than in the NC group (p < 0.0001). The C group patients had significantly higher rates of invasion to the mediastinal pleura, pericardium, lung, phrenic nerve, and chest wall and pleural dissemination than the NC group patients.ConclusionsCalcification reflects invasiveness of tumors to surrounding organs and tissues, and may thus predict thymoma stage and histologically high‐risk thymomas. Calcification in thymomas may also predict the pathological stage and help decide therapeutic methods and surgical approaches to treat thymomas based on the calcification status according to CT findings.

Clinicopathological features and current treatment outcomes of neuroendocrine thymic tumours.

Neuroendocrine thymic tumours (NETTs) are a distinct subgroup of rare malignancies. An international, multicentre retrospective analysis was used to study the clinicopathological features, current pattern of diagnosis, treatment and outcomes of patients with NETT. One hundred and forty-six NETT treated from 1989 to 2016 at 21 centres in China, Europe and North America were retrospectively collected and reclassified according to the World Health Organization histological type and International Thymic Malignancy Interest Group (ITMIG)/International Association for Studies in Lung Cancer (IASLC)/Union for International Cancer Control (UICC) staging. Clinicopathological features, diagnostic and therapeutic approaches and outcomes were investigated. Results in the earlier and latter halves of the study period were also compared. The pretreatment work-up relied exclusively on computed tomography in 85.6% (125/146) of cases. Most patients had advanced disease, with 32.2% (47/146) having lymph node involvement. Higher-grade histological type was associated with more advanced disease (P < 0.05). Induction therapies and surgical procedures were used more often in the latter half of the study. However, the complete resection rate remained unchanged, being 71.5% (98/137) in the whole group. Complete resection was associated with significantly longer 5-year overall survival (77.2% vs 51.2%; P < 0.001) than incomplete or no resection. Significant survival differences were seen with the T, N and M categories of ITMIG/IASLC/UICC staging. Poorly differentiated carcinoma, ITMIG/IASLC/UICC stage IIIa or above and incomplete or no resection were independent risk factors for worse survival. No survival difference was noted between the earlier and the latter halves of the study (58.2% vs 71.9%; P = 0.299). Current management similar to that for thymomas is unsatisfactory in providing disease control or long-term survival for patients with NETT. Specific diagnostic tools and novel therapeutic agents are needed to improve management outcomes of this disease.

Diet and gastric cancer

Context: Gastric cancer is the fifth most common malignancy, with a high incidence in Eastern Asian countries. Diet is an important risk factor in the genesis of gastric cancer, and the fact that it is modifiable warrants it to be studied extensively in relation to various clinicopathological parameters of gastric cancer. Aims: The present study was undertaken to study the dietary habits (vegetarian/nonvegetarian) among gastric carcinoma patients in the Indian context. Materials and Methods: We studied 100 consecutive cases of gastric carcinoma excluding tumors at gastroesophageal junction. Clinical data regarding food habits in the patients were collected by personal enquiry. Pathological characteristics including size, site, gross appearance, Lauren's histological type, and the World Health Organization (WHO) histological type were noted. Data analysis was done using Chi-square test. Results: Sixty-nine percent of gastric cancer patients were vegetarians and 31% were nonvegetarians. Statistically significant association between nonvegetarian diet and gastric cancer location at the lesser curvature was found (P ≤ 0.001). No statistically significant association between diet and gross appearance, Lauren's, and WHO histological type of gastric cancer was found. Conclusions: For anatomical locations, most gastric cancers located at lesser curvature had been developed among nonvegetarian patients, whereas we did not observe diet to be related to gross appearance and histological type of gastric carcinoma.

Long-term survival after R0 resection of thymoma

Background The aim of this study was to evaluate the results of R0 resection of thymoma to identify prognostic factors for long-term outcomes. Methods Data of 62 patients (28 male, 34 female) with a mean age of 47.26 ± 14.42 years, who underwent R0 resection for thymoma and were followed-up between February 2004 and March 2016, were analyzed retrospectively. Results Eight patients had a video-assisted thoracoscopic thymectomy and 54 had a transsternal extended thymectomy. During a mean follow-up of 128.67 ± 7.95 months, regional recurrence of thymoma was observed in 9 (14.5%) patients. Overall 5- and 10-year survival rates were 85.36% and 78.20%, respectively. The 5- and 10-year survival rates in patients aged < 50 years were significantly better than in those aged ≥ 50 years (92% and 72% vs. 88% and 39%, p < 0.0001). The 10-year overall survival of patients in Masaoka stage I and II was better than those in stage III (88.9%, 78.4%, 69.8%, respectively, log-rank p < 0.001). The 10-year survival of patients with World Health Organization histological type A, AB, and B1 thymomas was better than those with type B2 and B3 (log-rank test p < 0.001). In multivariate analysis, age < 50 years ( p = 0.001), Masaoka stage ( p = 0.006), histological type ( p = 0.001), and recurrence ( p = 0.04) were independent prognostic factors for survival. Conclusion Our study indicates that age < 50 years, Masaoka stage, histological type, and recurrence are the determinants of survival in surgically resected cases of thymoma.

Odontogenic tumours in Nigeria: A multicentre study of 582 cases and review of the literature.

BackgroundThe objective of this study was to classify the various types of odontogenic tumours (OTs) using the newly updated 2017 world health organization (WHO) histological typing and to analyze the prevalence of these tumours among Nigerians as well as to compare the results obtained with reports from world-wide studies.Material and MethodsThe records of four major tertiary hospitals in Nigeria were reviewed over a 12-year (2004-2015) period. Lesions diagnosed as odontogenic tumours were classified into four groups according to the 2017 WHO histological typing. Data which consisted of age, sex and site were analyzed using SPSS for Window (version 20.0; SPSS Inc., Chicago, IL) and frequency tables were computed.ResultsA total of 582 OTs were recorded and reviewed, benign OTs were 573 (98.5%) cases and malignant OTs were 9 (1.5%) cases. Of the benign OTs, the epithelial OTs were the commonest (500; 86%) while the benign mixed OTs were the least frequent (21; 3.6%). The mean age was 30±14 years (age range of 3–77years) and the peak age was in the third decade (197; 33.8%) of life. There was slight male gender and strong mandibular site predilection. Ameloblastoma, was the most frequent OT and it accounted for 75.5% of the OTs, followed by adenomatoid odontogenic tumour (8.1%) and odontogenic myxoma (7.2%). Malignant OTs accounted for 1.5% of the OTs.ConclusionsOTs show a geographic variation with tendency for prevalence of the epithelial OTs in Africa. Ameloblastoma has a high prevalence among Nigerians and is the most common OTs in Africa. Prevalence of odontoma is relatively low in developing African countries like Nigeria when compared to the prevalence in developed countries. Key words:Odontogenic tumours, WHO classification, Nigerians.

Long term oncological outcome of thymoma and thymic carcinoma - an analysis of 235 cases from a single institution.

Background and objectivesThymoma has a variable long-term oncological outcome after surgical resection. Survival and tumor recurrence were analyzed to determine the predisposing factors for tumor recurrence.MethodsA total of 235 patients who underwent surgery for thymoma or thymic carcinoma from December 1997 to March 2013 were analyzed using Masaoka staging system and World Health Organization (WHO) histological classification. Surgical intervention included extended thymothymectomy via median sternotomy and thymomectomy via thoracotomy/ video-assisted thoracoscopic surgery (VATS).ResultsThe median duration of follow-up was 105 months (12–198 months). Among these 235 patients, recurrence was observed in 25 patients (10.7%). according to Masaoka stage I, IIA, IIB, III, IVA, IVB, recurrence rates were 1/65(1.5%), 8/106(7.5%), 1/32(3.1%), 6/20(30.0%), 8/10(80.0%), 1/1(100.0%), respectively. Disease or treatment-related mortality was observed in 13 patients. Overall survival rate was 94.4%. After univariate analysis, predisposing factors for tumor recurrence included Masaoka stage, WHO histologic type, tumor size, adjuvant therapy and margin status.ConclusionsDue to the indolent behavior of thymoma, tumor recurrence appears to be a better assessment of oncological outcome rather than survival. Factors associated with tumor recurrence include Masaoka stage, WHO histologic type, tumor size, adjuvant therapy and margin status.

Effect of World Health Organization (WHO) Histological Classification on Predicting Lymph Node Metastasis and Recurrence in Early Gastric Cancer.

BackgroundThe World Health Organization (WHO) histological classification for gastric cancer is widely accepted and used. However, its impact on predicting lymph node metastasis and recurrence in early gastric cancer (EGC) is not well studied.Material/MethodsFrom 1987 to 2005, 2873 EGC patients with known WHO histological type who had undergone curative resection were enrolled in this study. In all, 637 well-differentiated adenocarcinomas (WD), 802 moderately-differentiated adenocarcinomas (MD), 689 poorly-differentiated adenocarcinomas (PD), and 745 signet-ring cell adenocarcinomas (SRC) were identified.ResultsThe distribution of demographic and clinical features in early gastric cancer among WD, MD, PD, and SRC were significantly different. Lymph node metastasis was observed in 317 patients (11.0%), with the lymph node metastasis rate being 5.3%, 14.8%, 17.0%, and 6.3% in WD, MD, PD, and SRC, respectively. Univariate and multivariate analyses indicated that gender, tumor size, gross appearance, depth of invasion, and WHO classification were significantly associated with lymph node metastasis. Recurrence was observed in 83 patients (2.9%), with the recurrence rate being 2.2%, 4.5%, 3.0%, and 1.6% in WD, MD, PD, and SRC, respectively. Multivariate analysis confirmed that MD, elevated gross type, and lymph node metastasis were independent risk factors for recurrence in EGC. MD patients showed worse disease-free survival than non-MD patients (P=0.001).ConclusionsWHO classification is useful and necessary to evaluate during the perioperative management of EGC. Treatment strategies for EGC should be made prudently according to WHO classification, especially for MD patients.

Tumor perimeter and lobulation as predictors of pleural recurrence in patients with resected thymoma

ObjectivesRecurrence of resected thymoma frequently occurs during follow-up, with pleural recurrence as the most common type. The aim of our study was to identify risk factors for pleural recurrence after complete resection of thymoma by investigating clinical, radiological, surgical, and pathological findings. Materials and methodsRetrospective study was performed with 309 patients who had undergone complete resection of thymoma between January 2000 and December 2013. Among these cases, the patients were divided into the no pleural recurrence group (n=285) and the pleural recurrence group (n=24). Radiologic parameters such as maximum tumor diameter, tumor perimeter that contacted the lung (TPCL) and lobulated tumor contour were measured based on computed tomography. A multivariate analysis was performed to estimate risk factors for pleural recurrence including maximum tumor diameter, TPCL, lobulated tumor contour, World Health Organization (WHO) histologic classification, and Masaoka-Koga (M-K) stage. ResultsThe median follow-up period was 62 months. The pleural recurrence rate was 7.8% (24/309). After univariate analysis, longer maximum tumor diameter (p<0.001), longer TPCL (p<0.001), lobulated tumor contour (p=0.001), WHO histologic type B2, B3 (p=0.002), and M-K stage III/IV (p<0.001) demonstrated significant differences with risk factors of pleural recurrence. Multivariate analysis revealed that TPCL (per 1cm increase: hazard ratio [HR]: 1.040, 95% confidence interval [CI]: 1.019–1.061, p<0.001), lobulated tumor contour (HR: 5.883, CI: 1.201–28.824, p=0.029), WHO histologic classification B2/B3 (HR: 5.331, CI: 1.453–19.558, p=0.012) and advanced M-K stage (HR: 3.900, CI: 1.579–9.632, p=0.003) were significantly associated with pleural recurrence. ConclusionTPCL and lobulated tumor contour as well as WHO histologic classification and M-K stage were independent predictors of pleural recurrence after thymoma resection. Our study demonstrated that radiologic parameters could be useful predictor of pleural recurrence in patients with resected thymoma.

Thymic epithelial tumors: Can fluorodeoxyglucose positron emission tomography help in predicting histologic type and stage?

To study the utility of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting (1) the World Health Organization (WHO) histologic type and differentiating low-risk from high-risk types. (2) Tumor stage and differentiate early from advanced stage disease. Patients with thymic epithelial neoplasia who underwent a pretreatment FDG-PET study were included. Tumor maximum standardized uptake value (SUVmax) was correlated with the WHO histologic type and also with the Masaoka-Koga (MK) staging system. Patients with WHO Type A, AB, and B1 were classified as low risk and those with B2 and B3 as high risk. Thymic carcinomas belonged to Type C. Patients with MK Stage I and II disease were grouped as early stage and those with Stage III and IV as an advanced stage. Differences in SUVmax between the various groups were calculated. The SUVmax of thymic carcinomas was significantly higher as compared to low-risk (P = 0.001) and high-risk groups (P = 0.007). The SUVmax of high-risk group was also significantly higher than the low-risk group (P = 0.002). SUVmax cutoff of 6.5 was able to differentiate thymic carcinomas from thymomas with 100% sensitivity and 87.2% specificity. The SUVmax in patients with advanced stage disease showed a higher trend compared to those with early stage, but the difference was not significant (P = 0.167). PET can differentiate thymic carcinomas from rest of the thymoma subtypes by the virtue of their higher FDG uptake. It can also provide valuable information in differentiating high-risk from low-risk thymomas and in predicting disease stage.

Patterns and predictors of recurrence after radical resection of thymoma

BackgroundRecurrence of thymomas even after complete resection is common, but the relapse patterns remain controversial. This study aimed to define the patterns and predictors of relapse after complete resection of thymoma. MethodsA single-institution retrospective study was performed with 331 patients who underwent radical resection of thymoma between 1991 and 2012. ResultsAfter a median follow-up of 59months, the recurrence rate was 6.9% (23/331). Relapse occurred in 23 patients with the pleura (14) and tumor bed (6) as the most common sites of recurrence. According to the definitions of the International Thymic Malignancy Interest Group, 10 (43.5%) patients had local relapse, 15 (65.2%) had regional relapse, 10 (43.5%) had distant relapse. The difference in survival following relapse between lung and regional relapse was statistically significant (P=0.027) but that between lung and distant relapse was not (P=0.808). The recurrence rates correlated with the initial Masaoka stage. Further, recurrence also correlated with World Health Organization (WHO) tumor type. The recurrence-free survival rates in patients with tumor size ⩾8cm were worse than those of patients with tumor size <8cm (P=0.007). Tumor size was also correlated with stage (r=0.110). As tumor becomes larger, the stage is more advanced (P=0.023). Multivariate analysis showed that Masaoka stage (P=0.005), tumor size (P=0.033), and WHO histological type (P=0.046) were predictive factors of relapse. ConclusionRegional recurrence is the most common relapse pattern but local and distant relapse are also common. Advanced Masaoka stage, larger tumor size, and type B3 are risk factors of recurrence. Lung relapse should be considered distant relapse. Further, tumor size was correlated with Masaoka stage and therefore should be considered in the staging system.

Recurrence after thymoma resection according to the extent of the resection

BackgroundComplete resection of the thymus is considered appropriate for a thymoma resection because any remaining thymic tissue can lead to local recurrence. However, there are few studies concerning the extent of thymus resection. Therefore, we conducted a retrospective study to investigate whether recurrence following thymoma resection correlated to the extent of resection.MethodsBetween 1986 and 2011, a total of 491 patients underwent resection of thymic epithelial tumors with curative intent. Of those, we excluded patients with an undetermined World Health Organization (WHO) histologic type, patients with type C thymoma, and patients who underwent incomplete resection (n = 21). The remaining 342 patients were reviewed retrospectively and compared recurrence according to the extent of resection.ResultsExtended thymectomy was performed in 239 patients (69.9%) and limited thymectomy was performed 103 patients (30.1%). In the extended thymectomy group, 29 recurrences occurred, and in the limited thymectomy group, 10 recurrences occurred.Comparing rates of freedom from recurrence between two groups, there was no significant statistical difference in total recurrence (p =0.472) or local recurrence (p =0.798). After matching patients by stage and tumor size, there was no significant difference in freedom from recurrence between the two groups (p = 0.162). Additionally, after adjusting for histologic type and MG, there was also no significant difference (p = 0.125) between groups.ConclusionsNo difference in the rate of recurrence was observed in patients following limited thymectomy compared with extended thymectomy.

APKCλ/ι is a beneficial prognostic marker for pancreatic neoplasms

Pancreatic cancer is a lethal disease. Overall survival is typically 6 months from diagnosis. Determination of prognostic factors in pancreatic cancer that would allow identification of patients who could potentially benefit from aggressive treatment is important. However, until date, there are no established reliable prognostic factors for pancreatic cancer patients. Herein, we propose a beneficial biomarker which is significantly correlated with the prognosis in pancreatic cancer patients. Atypical protein kinase C λ/ι (aPKCλ/ι) is overexpressed and has been implicated in the progression of several cancers. We tested the expression levels of aPKCλ/ι in two types of pancreatic neoplasm, pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs), by immunohistochemistry. Examination of the aPKCλ/ι expression levels in surgically resected specimens of PDCA (n = 115) demonstrated that the expression levels of aPKCλ/ιin PDAC had prognostic implications, independent of the Tumor-Node-Metastasis classification and World Health Organization tumor grade. In the case of IPMNs (n = 46) also, the expression levels of aPKCλ/ιin IPMN were found to be of prognostic importance, independent of the World Health Organization histological grade or morphological type. Interestingly, high expression levels of aPKCλ/ι were significantly correlated with a worse histological grade (p = 0.010) and advanced stage of the tumor (p = 0.0050) in IPMN patients. These findings suggest that high expression levels of aPKCλ/ι could be involved in the malignant transformation of IPMNs. Based on these observations, we propose the expression level of aPKCλ/ι as a prognostic marker common to different types of pancreatic neoplasms.

Predictors of Recurrence after Thymoma Resection

PurposeRecurrence rate is considered a better measure of clinical outcomes after thymoma resection than overall survival due to the indolent behavior of thymomas. This study was designed to determine predictors of recurrence after thymoma resection.Materials and MethodsA single-institution, retrospective study was performed, including 305 patients who had undergone thymoma resection between 1986 and 2009.ResultsAmong 305 patients, recurrence was observed in 41 patients (13.4%). The recurrence rates were 0% (0/19), 6.3% (4/63), 4.2% (2/48), 18.6% (11/59) and 20.7% (24/116) for type A, AB, B1, B2 and B3 tumors, respectively. The recurrence rate according to Masaoka stage was 6.1% (8/132), 11.4% (13/114), 26.8% (11/41) and 50.0% (9/18) for stages I, II, III and IV, respectively. After univariate analysis, completeness of resection (R0 versus R1), World Health Organization (WHO) histologic type (A, AB, B1 versus B2, B3), Masaoka stage, and size of tumor (<8 cm versus ≥8 cm) demonstrated significant differences with freedom from recurrence. Upon multivariate analysis, Masaoka stage was the only independent predictor of recurrence.ConclusionWHO histologic type, Masaoka stage, and size of tumor were associated with recurrence. Particularly, Masaoka stage was the only independent predictor of recurrence after thymoma resection.

World Health Organization classification of thymomas provides significant prognostic information for selected stage III patients: evidence from an international thymoma study group

Information regarding prognosis of thymoma patients stratified by both World Health Organization classification and Masaoka staging system is very limited. Analyze 5-year survival data from a large number of thymoma patients stratified by both World Health Organization histologic type and Masaoka stage using meta-analysis. Perform power analysis to estimate the number of cases that would be needed to test the null hypothesis to a power of 80%. Five-year survival data from 905 thymoma patients treated with thymectomy at seven hospitals in America, Japan, Korea, India, Italy, and Germany. Survival data was reported as "dead" or "alive" to facilitate meta-analysis. Significant differences were detected only when comparing survival rates of thymoma patients in stages I to III with those of stage IV disease. Analysis by World Health Organization histologic type and stage yielded significant differences only in patients with thymomas A vs. B2 and A vs. B3 in stage III disease. No significant data heterogeneity was detected with funnel plots and Egger's regression test. Power analysis estimated that a study with 7077 patients is needed to evaluate the prognostic significance of all thymomas stratified by both World Health Organization histologic type and stage to a power of 80%. Selected World Health Organization histologic types are significantly associated with prognosis in stage III thymoma patients and may help select individuals benefiting from neoadjuvant therapy. Power analysis shows that studies with much larger number of patients are needed to exclude the possibility that histologic type may provide significant prognostic information in other stages of the disease.

Invited Commentary

The authors [1Prokakis C. Koletsis E. Salakou S. et al.Modified maximal thymectomy for myasthenia gravis: effect of maximal resection on late neurologic outcome and predictors of disease remission.Ann Thorac Surg. 2009; 88: 1638-1646Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar] describe the results of a “modified maximal thymectomy” in a series of patients who have myasthenia gravis with and without a thymoma. The authors claim the operation is analogous to a T-4 maximal thymectomy as described by Jaretzki and colleagues [2Jaretzki A. Steinglass K.M. Sonett J.R. Thymectomy in the management of myasthenia gravis.Sem Neurol. 2004; 24: 49-62Crossref PubMed Scopus (73) Google Scholar], but in reality it is a T-3b thymectomy. Although it is doubtful that there is much of a difference in outcome between these two “aggressive” thymectomy operations, a T-4 thymectomy implies a cervical incision and radical resection of all fat around the cervical thymus. The details of the evaluation of the neurologic outcome are somewhat vague. I would assume the two neurologists who are co-authors performed all the neurologic evaluations personally within a reasonably short time period, but we are not told these details in the article. The perioperative morbidity was very low, attesting to the clinical skills of the neurologist's preparation for surgery and surgical technique. The complete stable remission (CSR) rate was essentially the same for the patients with and without thymoma, as was the Kaplan Meir estimate and the mean time to a CSR. The absence of steroids in the preoperative treatment was a strong predictor of obtaining a CSR in both groups, whereas the World Health Organization histologic type also predicted a higher CSR rate in the patients with thymoma. Both of these observations have been made by others as noted in their references, but the reason why remains unknown. The strengths of this study include an apparent uniform operative approach during the long time period of the study, the low perioperative morbidity, the use of the Osserman classification to describe the preoperative condition of the patients, the use of the CSR as a “hard” end-point of the study, the relatively long mean follow-up, and the use of Kaplan-Meier actuarial analysis of the CSR rate, because it is a time-related event. The authors postulate that because they had a very low incidence of postoperative myasthenic crisis, it was attributable to early ligation of thymic veins. I believe this hypothesis is unfounded and rather premature. I believe it is more likely due to chance. Whether a T-3b thymectomy is superior to a transcervical T1b thymectomy is still unclear, because the patient populations reported are so dissimilar, as to make quick comparisons meaningless. A randomized trial would be ideal to settle this longstanding controversy. Due to a lack of equipoise on the part of surgeons, this trial is unlikely to ever happen. Perhaps an international group of interested neurologists and thoracic surgeons could agree what a common dataset requires and then submit cases to an independent for analyses with proper adjustment (perhaps with a propensity analysis) to attempt to settle this important question. Modified Maximal Thymectomy for Myasthenia Gravis: Effect of Maximal Resection on Late Neurologic Outcome and Predictors of Disease RemissionThe Annals of Thoracic SurgeryVol. 88Issue 5PreviewAlthough thymectomy is a standard practice of care in patients with myasthenia gravis, the best approach to thymic resection remains controversial. This study was conducted to assess the effect of maximal resection on neurologic outcome and identify predictors of disease remission. Full-Text PDF