Nationwide prospective registry database of patients with newly diagnosed untreated pleural mesothelioma in Japan.

Due to the scarcity of large-sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44-88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non-surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non-surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma.

Complications and Predictive Factors for Air Leak > 10 Days with Neoadjuvant Chemotherapy Followed by Pleurectomy/Decortication for Malignant Pleural Mesothelioma.

BACKGROUND: A few studies have reported the incidence and clinical implications of complications after pleurectomy/decortication (P/D). OBJECTIVE: The aim of this study was to assess the details of complications and predictive factors of particularly durable air leak with P/D. METHODS: Data on 163 consecutive patients who underwent neoadjuvant chemotherapy (NAC) followed by P/D for malignant pleural mesothelioma between September 2012 and May 2020 at our institution were retrospectively analyzed. Postoperative complications and the significance of various preoperative risk factors for air leak > 10 days (AL10) to identify the group having a higher risk for particularly durable air leak were investigated. Risk factors for AL10 were sought using univariate and multivariate analyses. RESULTS: Of 163 patients, 30- and 90-day mortality was 0.6% and 2.5%, respectively. Eighty-four (51.4%) patients experienced grade III or worse postoperative complications according to the Clavien-Dindo classification. The median duration of air leak was 7 postoperative days. AL10 occurred in 53 (32.5%) patients. Fifty-eight patients (35.6%) underwent pleurodesis and five patients (3.1%) underwent reoperation to control the air leak. On univariate analysis, performance status (PS; p = 0.003), prognostic nutritional index (p = 0.01), and pleural effusion (p = 0.04) were statistically significant risk factors for AL10, while on multivariate analysis, PS (odds ratio 4.0, 95% confidence interval 1.3-12.7; p = 0.02) remained the only variable predicted for AL10. CONCLUSIONS: Recent postoperative mortality rates in NAC followed by P/D are quite acceptable. Approximately one in every three patients experienced AL10, and PS may be a risk factor associated with AL10.

Poor Prognostic Factors in Patients with Malignant Pleural Mesothelioma Classified as Pathological Stage IB According to the Eighth Edition TNM Classification.

INTRODUCTION: The change in TNM classification of malignant pleural mesothelioma (MPM) between the seventh and eighth edition classifications has resulted in the downstaging of many advanced-stage patients into pathological stage IB. Many mesotheliomas without lymph node metastasis have been classified as stage IB in the eighth edition classification. Stage IB mesotheliomas comprised a heterogeneous group with different prognosis. It is necessary to clarify the prognostic factors in this group. METHODS: Between September 2009 and August 2016, a total of 89 patients with MPM underwent curative intent surgery [pleurectomy decortication n = 57 (64.1%), extrapleural pneumonectomy n = 32 (35.9%)] at our institution. Of these, 40 were reclassified as stage IB according to the eighth edition TNM classification. Independent unfavorable prognostic factors were identified by univariate analyses using the log-rank test and Cox proportional hazards regression models. RESULTS: Three independent significant factors were identified that indicated an unfavorable prognosis: a nonepithelioid subtype, lymphovascular invasion, and preoperative forced expiratory volume in 1 s (FEV1) < 2000 ml. Patients with no, one, and two of these risk factors showed 3-year overall survival probabilities of 94.7, 62.5, and 0%, respectively. The 3-year survival of patients with one factor did not differ significantly from that of patients with stage III MPM, whereas that of patients with two factors was significantly shorter (p = 0.015). CONCLUSIONS: Independent poor prognostic factors for patients with stage IB MPM patients, allowing subgroups with poorer and more favorable prognoses to be identified. This should help personalize decisions on adjuvant chemotherapy.

Post-recurrence chemotherapy for mesothelioma patients undergoing extrapleural pneumonectomy.

BACKGROUND: Additional chemotherapy is often not feasible in patients with recurrent malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP), due to deteriorated cardiopulmonary reserve. We thus examined the feasibility and efficacy of additional chemotherapy in patients with recurrent MPM after EPP. METHODS: A retrospective review was conducted of 59 consecutive patients who underwent bi-/tri-modal treatment with induction chemotherapy, EPP, and radiation therapy from July 2004 to August 2013 at Hyogo College of Medicine (Nishinomiya, Japan). RESULTS: Of 59 patients, 39 (male/female = 31/8, right/left = 15/24, pathological stage I/II/III/IV = 1/7/23/3, bi-/tri-modality = 27/12) relapsed at a median age of 62 (range 37-71) years. The median time to recurrence after EPP was 11.6 months. Of the 39 relapsed patients, 12 received best supportive care alone, six started but discontinued chemotherapy, and the remaining 21 (53%) completed more than three cycles of intravenous chemotherapy. The median survival time after EPP was significantly longer in 21 patients who received additional chemotherapy than in 18 patients who did not (39.2 vs. 12.2 months, P = 0.009). CONCLUSIONS: Additional systemic chemotherapy was successfully administered in more than 50% of relapsed patients after bi-/tri-modal treatment, which included EPP, and resulted in a longer survival in comparison with best supportive care alone.

Current surgical strategies for malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. The main components of multimodality treatment include surgery, chemotherapy, and radiation therapy. Surgery remains controversial. Two procedures are currently offered: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). The recent scientific literature suggests that P/D is a well-tolerated procedure, with the potential of becoming a default procedure in multimodality regimens. However, the precise treatment schemes and surgical procedures are yet to be established. In our study, we review the advantages and disadvantages of EPP and P/D, summarize the post-EPP and post-P/D observations (including mortality, morbidity, and median survival time), and discuss the choice of surgical technique (EPP vs. P/D). Moreover, we highlight the aspects of the multimodality treatments that are offered to MPM patients, including chemotherapy, radiotherapy, intensity-modulated radiation therapy, and other types of therapy.

[Current surgical therapy for malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a rare tumor and associated with very poor prognosis. The median survival time( MST) was 8.9 months for those treated by palliative care only. For a radical treatment, total removal of the tumor is the main therapy as well as other solid tumors, but these diffuse and infiltrate growth pattern of tumor make it difficult. The MST was 13 months for patients treated by surgery only. On the other hand, MST using pemetrexed/cisplatin was 12.1 months. There are negative opinions for invasive surgical treatment such as extrapleural pneumonectomy (EPP). Currently surgical treatment of mesothelioma is conducted as part of the multidisciplinary treatment combined with chemotherapy and radiation therapy.

Circulating tumor cells (CTCs) in malignant pleural mesothelioma (MPM).

PURPOSE: To investigate the diagnostic and prognostic value of circulating tumor cells (CTCs), a potential surrogate of micrometastasis, in malignant pleural mesothelioma (MPM). METHODS: We prospectively evaluated CTCs in 7.5 mL of peripheral blood sampled from patients with a suspicion of MPM. A semiautomated system was used to capture CTCs with an antibody against the epithelial cell adhesion molecule. RESULTS: Of 136 eligible patients, 32 were finally diagnosed with nonmalignant diseases (NM), and 104 had MPM. CTCs were detected in 32.7 % (34 of 104) of MPM patients but in only 9.4 % (3 of 32) of NM patients (P = 0.011). The CTC count was significantly higher in MPM patients than in NM patients (P = 0.007), and a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination between MPM and NM, with an area under ROC curve of 0.623 (95 % confidence interval, 0.523-0.723; P = 0.036). Among MPM patients, CTCs were more frequently detected in patients with epithelioid subtype (39.7 %, 31 of 78) than in those with nonepithelioid subtypes (11.5 %, 3 of 26; P = 0.016). Positive CTCs (CTC count ≥ 1) were a significant factor to predict a poor prognosis among epithelioid patients (median overall survival, 22.3 months for positive CTCs vs. 12.6 months for negative CTCs; P = 0.004) and not in nonepithelioid patients (P = 0.649). A multivariate analysis showed that positive CTCs were a significant and independent factor to predict a poor prognosis (hazard ratio, 2.904; 95 % confidence interval, 1.530-5.511; P = 0.001) for epithelioid MPM patients. CONCLUSIONS: CTC was a promising marker in diagnosis and prediction of prognosis in MPM, especially in epithelioid MPM.

Frequency of epidermal growth factor receptor mutations in Bangladeshi patients with adenocarcinoma of the lung.

BACKGROUND: Worldwide studies on lung adenocarcinoma have demonstrated a genetic divergence of the epidermal growth factor receptor (EGFR) pathway according to ethnicity, such as higher frequency of activated EGFR mutations among East Asian patients. However, such information is still lacking in some developing countries. METHODS: We investigated the frequency of EGFR mutations among Bangladeshi patients with adenocarcinoma of the lung. Fine-needle aspiration tissue samples were collected from 61 Bangladeshi patients. Polymerase chain reaction-single-strand conformation polymorphism was performed on extracted DNA for mutational analysis of EGFR exons 19 and 21. RESULTS: EGFR mutations were found in 14 of 61 (23.0 %) Bangladeshi patients. There was no significant difference in EGFR mutation rate with regard to patient's age, sex, smoking history, clinical stage of lung cancer, subtypes of adenocarcinoma, and tumor differentiation. CONCLUSION: The present study revealed that the EGFR mutation rate in Bangladeshi patients with adenocarcinoma of the lung was higher than in African-American, Arabian, and white Caucasian patients, and was lower than in East Asia.

Characteristic immunophenotype of solid subtype component in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinomas represent a morphologically heterogeneous tumor composed of an admixture of different histologic subtypes (lepidic, papillary, acinar, and solid subtype). The presence of a solid subtype component is reported to be associated with a poorer prognosis. The aim of this study was to evaluate the characteristic immunophenotype of the solid subtype component compared with the immunophenotypes of other components. METHODS: We analyzed the clinicopathological characteristics of stage I adenocarcinoma patients with predominant solid subtype disease. Furthermore, we immunostained adenocarcinomas with predominant lepidic, papillary, acinar, and solid subtype components (n = 23 each) for 10 molecular markers of tumor invasiveness and scored the results. RESULTS: Patients showing predominance of the solid subtype component (solid subtype adenocarcinoma) had a poorer prognosis than those showing predominance of the lepidic, papillary, or acinar component. Lymphovascular invasion was more often detected in solid subtype tumors than in others. The solid subtype component showed a significantly stronger staining intensity of laminin-5 expression than the lepidic, papillary, and acinar components (P < 0.001, P < 0.001, and P = 0.016, respectively). The fibronectin and vimentin expression levels were also significantly higher in the solid subtype component than in other components. This immunostaining character was validated by using mixed-subtype adenocarcinomas containing all four components in the same tumor. CONCLUSIONS: This study concluded that the solid subtype component in lung adenocarcinomas exhibit the invasive immunophenotype, including increased laminin-5 expression, compared with the other components, which may be associated with a poorer prognosis.

Circulating endothelial cell (CEC) as a diagnostic and prognostic marker in malignant pleural mesothelioma (MPM).

BACKGROUND: The purpose of this study was to investigate the diagnostic and prognostic value of circulating endothelial cell (CEC), a potential surrogate of tumor angiogenesis, in malignant pleural mesothelioma (MPM). METHODS: We prospectively evaluated CEC count in 4.0 mL of peripheral blood sampled from patients with a suspicion of MPM. An automated system was used to capture CECs with an anti-CD146 antibody. RESULTS: Of 109 eligible patients, 30 were finally diagnosed with non-malignant diseases, and 79 were with MPM. CEC count was significantly higher in MPM patients than in NM patients (mean CEC count, 120.3 and 39.9, respectively; P = 0.001), and a receiver operating characteristic (ROC) curve analysis showed that CEC provided a significant diagnostic performance in discrimination between MPM and nonmalignant diseases with an area under curve (AUC-ROC) of 0.700 (95 % confidence interval [95 % CI], 0.595-0.806; P = 0.001). Among MPM patients, CEC count was positively correlated with intratumoral microvessel density (MVD), a measurement of tumor angiogenesis (Spearman correlation coefficiency [r] = 0.444; P = 0.001). Higher CEC count (>50) was significantly associated with a poor prognosis (median overall survival, 11.4 months [95 % CI, 7.6-15.2] for higher CEC count patients versus 20.1 months [95 % CI, 16.0-24.2] for lower CEC count patients; P = 0.028). A multivariate analysis showed that higher CEC count was a significant and independent factor to predict a poor prognosis (hazard ratio [HR], 2.24, [95 % CI, 1.24-4.43]; P = 0.009). CONCLUSIONS: CEC, as a surrogate of tumor angiogenesis, was a promising marker in diagnosis and prediction of prognosis in MPM.

Practical approaches to diagnose and treat for T0 malignant pleural mesothelioma: a proposal for diagnostic total parietal pleurectomy.

Malignant pleural mesothelioma (MPM) remains suffering poor prognosis in spite of recent diagnostic and therapeutic progress. Although there is currently no established evidence, early diagnosis and early intervention may play a key role to improve prognosis of MPM, similarly to other malignancies. As pleural effusion is usually the first clinical sign of MPM, pleural effusion cytology is often the first diagnostic examination to be carried out. Since the sensitivity of pleural effusion cytology is approximately 60%, however, false-negative diagnosis is given to almost half of true MPM patients at this clinical step. One practical way to reduce the number of misdiagnosed MPM is to encourage performing thoracoscopic pleural biopsy unless definitive diagnosis other than MPM is established. There still remain a considerable number of patients with radiological/thoracoscopic T0 MPM who are misdiagnosed with nonspecific pleuritis after a complete investigation including thoracoscopic biopsies. Such patients will turn out to be malignant during follow-up period, although they have the best opportunity for long-term survival if only early therapeutic intervention is given. Currently, we are performing diagnostic total parietal pleurectomy in highly selected patients, who are characterized with strong clinical suspicion, positive pleural effusion cytology but uncertain pathological diagnosis, excellent cardiopulmonary reserve, and with written informed consent for highly invasive diagnostic surgery for pathologically unproven disease.

Control of air leakage during pleurectomy/decortication by the ventilation and anchoring method.

OBJECTIVES: We previously established a novel method of lung repair called the ventilation and anchoring (V/A) method. We evaluated the usefulness of the V/A method for controlling air leakage during pleurectomy/decortication (P/D). METHODS: For this study, we enrolled patients with malignant pleural mesothelioma (MPM) who planned to receive P/D. Our lung repair method involves (1) suturing lung parenchyma for an apparent injured lesion and (2) coating the lung parenchyma with fibrin glue (FG) using the V/A method. The tidal volume (TV) was measured under pressure-controlled ventilation in the ipsilateral-affected lung 10 times at the following four points: after thoracotomy, at completion of visceral pleurectomy, after suturing lung parenchyma, and 5 min after coating with FG. The primary endpoint was the mean TV (mTV) change, and the secondary endpoints were the duration of air leakage and incidence of pleurodesis. RESULTS: Between April 2014 and April 2016, 25 patients of the 29 consecutive patients enrolled were eligible. The mTV significantly decreased after completion of visceral pleurectomy but significantly increased after repair of the lung parenchyma, especially after coating with FG. The median duration of postoperative air leakage was 4 days (range: 2-19 days). Postoperative air leakage > 7 days was observed in 11 (44%) patients. Of these 11 patients, 6 received pleurodesis; however, no further revision was needed. CONCLUSIONS: Significant increases in TV were observed after coating with FG via the V/A method during P/D. Coating with FG using the V/A method can contribute to a reduction in air leakage during P/D.

Multicentre, prospective, observational study investigating the most appropriate surgical option that can prevent the recurrence of primary spontaneous pneumothorax after surgery: the PATCH study, protocol.

INTRODUCTION: Thoracoscopic surgery is performed for refractory or recurrent primary spontaneous pneumothorax (PSP). To reduce postoperative recurrence, additional treatment is occasionally adopted during surgery after bulla resection. However, the most effective method has not been fully elucidated. Furthermore, the preference for additional treatment varies among countries, and its efficacy in preventing recurrence must be evaluated based on settings tailored for the conditions of a specific country. The number of registries collecting detailed data about PSP surgery is limited. Therefore, to address this issue, a prospective multicentre observational study was performed. METHODS AND ANALYSIS: This multicentre, prospective, observational study will enrol 450 participants aged between 16 and 40 years who initially underwent PSP surgery. Data about demographic characteristics, disease and family history, surgical details, and CT scan findings will be collected. Follow-up must be conducted until 3 years after surgery or in the event of recurrence, whichever came first. Patients without recurrence will undergo annual follow-up until 3 years after surgery. The primary outcome is the rate of recurrence within 2 years after surgery. A multivariate analysis will be performed to compare the efficacy of different surgical options. Then, adverse outcomes correlated with various treatments and the feasibility of treatment methods will be compared. ETHICS AND DISSEMINATION: This study was approved by the local ethics committee of all participating centres. The findings will be available in 2025, and they can be used as a basis for clinical decision-making regarding appropriate options for the initial PSP surgery. TRIAL REGISTRATION NUMBER: NCT04758143.

Treatment of bronchial fistula after extraplural pneumonectomy using flexible bronchoscopy with the administration of OK432, fibroblast growth factor basic and fibrin glue sealant.

Treatment options for bronchial fistula (BF) after pneumonectomy are often limited and carry significant morbidity and mortality. The patient underwent right extrapleural pneumonectomy for malignant pleural mesothelioma had BF without macroscopic fistula found by bronchography. We treated this minor BF using bronchoscopy with the administration of OK-432, fibroblast growth factor basic, and fibrin glue sealant. Two weeks after this treatment, we confirmed the improvement of the fistula by bronchography. Bronchoscopic therapy for BF was useful for a small, early fistula without infection.

Three tumor markers for improved efficacy in the management of patients with malignant pleural mesothelioma.

BACKGROUND: Evaluation of tumor markers may facilitate follow-up of malignant pleural mesothelioma (MPM). We aimed was to evaluate the value of tumor markers for monitoring and predicting recurrence in patients with MPM. METHODS: In total, 152 patients who underwent curative-intent surgery after induction chemotherapy for MPM between July 2004 and December 2017 were retrospectively reviewed. Preoperative and postoperative (≤3 months after surgery) levels of soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (Cyfra21-1), and tissue polypeptide antigen (TPA) and rates of recurrence and non-recurrence were evaluated. Factors associated with recurrence-free survival (RFS) were assessed using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: Of the 152 patients, the positive rates of preoperative SMRP, Cyfra21-1, and TPA, levels were 26.7%, 8.6%, 9.6%, respectively; the respective postoperative levels were 4.0%, 6.3%, and 6.5%; the respective levels in patients with recurrence were 39.3%, 31.4%, 28.6%; the respective levels in patients with no recurrence were 3.7%, 0.0%, 3.8%. Nearly half (45.2%) of the patients with recurrence exhibited an increase in one or more tumor marker levels. Multivariate analysis revealed that the preoperative positive rates of one or more of the three tumor markers (hazard ratio: 1.8, 95% confidence interval: 1.1-2.8; P=0.02) were independent significant predictors of recurrence. CONCLUSIONS: The positive rates of SMRP, Cyfra21-1, and TPA in recurrence-free patients were extremely low, with high specificity. Preoperative levels of SMRP, Cyfra21-1, and TPA, which identified patients with a high risk for recurrence, could improve management of patients with MPM.

Clinical Outcomes With Recurrence After Pleurectomy/Decortication for Malignant Pleural Mesothelioma.

BACKGROUND: Most patients with malignant pleural mesothelioma experience recurrence after treatment. However no clinical studies have evaluated postrecurrence survival after pleurectomy/decortication for malignant pleural mesothelioma. This study aimed to clarify postrecurrence survival, treatment, prognostic factors, and recurrence pattern after pleurectomy/decortication. METHODS: We conducted a retrospective cohort study of 90 patients who underwent neoadjuvant chemotherapy followed by pleurectomy/decortication at our hospital between September 2012 and December 2017. Survival and recurrence were calculated using the Kaplan-Meier method with the log-rank test. Clinical factors related to postrecurrence survival were assessed using multivariate analysis with the Cox proportional hazards model. RESULTS: Of 90 patients, 57 (63.3%) developed recurrence. The 1- and 3-year recurrence-free survival rates were 69.7% and 34.0%, respectively (median recurrence-free survival time, 19.0 months). With regard to initial recurrence, 39 patients (68.4%) developed local recurrence, 6 (10.5%) developed distant recurrence, and 12 (21.1%) developed both local and distant recurrences. The 1-year postrecurrence survival rate was 59.5% (median post-recurrence survival time, 14.4 months). Forty-three patients (75.4%) underwent a postrecurrence treatment. Multivariate analysis revealed that postrecurrence treatment (hazard ratio, 0.2; 95% confidence interval, 0.07-0.55; P = .002), performance status 0 to 1 (hazard ratio, 0.24; 95% confidence interval, 0.08-0.76; P = .01), and disease-free interval more than 12 months (hazard ratio, 0.4; 95% confidence interval, 0.16-0.99; P = .04) were the independent, favorable, and significant prognostic factors of postrecurrence survival. CONCLUSIONS: Postrecurrence survival after pleurectomy/decortication is acceptable, and postrecurrence treatment, performance status, and disease-free interval are important prognostic factors of postrecurrence survival.

Surgical Risk and Survival Associated With Less Invasive Surgery for Malignant Pleural Mesothelioma.

We compared less invasive surgery with conventional surgery for malignant pleural mesothelioma (MPM). We retrospectively reviewed consecutive patients with MPM who received surgery at Hyogo College of Medicine between July 2004 and April 2016. Patients underwent multimodal treatment comprising chemotherapy (neoadjuvant and/or adjuvant) and surgery with or without 54 Gy hemithoracic radiotherapy. Patients were grouped into 3 groups according to the surgery intended: Conventional extrapleural pneumonectomy was intended in Group 1 (until August 2009); less invasive extrapleural pneumonectomy was intended in Group 2 (after September 2009); pleurectomy/decortication was intended in Group 3 (after September 2012). We included 152 patients (median age 64 [37-71] years; 131 men, 21 women), mostly with epithelioid subtypes (91.4%). Of them, 149 (98.0%) underwent neoadjuvant chemotherapy and 117 (77.0%) underwent surgery (60 had extrapleural pneumonectomy and 57 had pleurectomy/decortication). Macroscopic complete resection was achieved in 94.9% (111/117), and the mortality rates at 30 and 90 days were 1.7% (2/117) and 3.4% (4/117), respectively. The overall median survival time and progression-free survival for all 152 patients were 34.9 and 17.4 months. The overall median survival time for Groups 1, 2, and 3 were 18.5, 41.9, and 43.4 months, respectively. The progression-free survival for Groups 1, 2, and 3 were 12.0, 24.5, and 21.8 months, respectively. Compared with conventional surgical techniques, less invasive surgery for MPM yielded lower surgical risks and comparable or improved survival.

The mTOR Signaling Pathway Is Associated With the Prognosis of Malignant Pleural Mesothelioma After Multimodality Therapy.

BACKGROUND/AIM: We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. PATIENTS AND METHODS: Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). RESULTS: On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. CONCLUSION: The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.

Pleural thickness after neoadjuvant chemotherapy is a prognostic factor in malignant pleural mesothelioma.

OBJECTIVES: Definitive diagnosis of the T-component is sometimes challenging in malignant pleural mesothelioma (MPM). Pleural thickness has been reported to be a prognostic factor for MPM and is a potential T-component. METHODS: We conducted a historical cohort study of patients who underwent neoadjuvant chemotherapy (NAC) and curative-intent surgery as a multimodal treatment for MPM from January 2007 to June 2016. The maximum measurement of pleural thickness among 3 levels and the sum at each level determined using axial computed tomography imaging before and after NAC were termed as "max" and "sum," respectively. We assessed the association between pleural thickness and the primary and secondary end points of overall survival and recurrence-free survival. Survival was analyzed using the Kaplan-Meier curve, log rank test, and multivariate Cox regression model. RESULTS: We enrolled 105 patients. We excluded 1 because of missing data; thus, the sample size was 104. The median follow-up period was 29.1 months with recurrence in 78 patients (70.3%) and death in 67 (60.4%). Max and sum ranged from pre (before NAC) values of 0 to 35 (median, 6.05) and 0 to 97 (median, 12.9) to post (after NAC) values of 0 to 30.8 (median, 4.25) and 0 to 67.0 (median, 9.25), respectively. Post values max and sum were associated with overall survival and recurrence-free survival. Post sum values were associated with recurrence (adjusted hazard ratio, 2.59; 95% confidence interval, 1.42-3.83) and death (adjusted hazard ratio, 2.13; 95% confidence interval, 1.16-4.52), respectively. CONCLUSIONS: Pleural thickness after NAC was an independent prognostic factor in patients who underwent multimodal treatment.

Perivascular epithelioid cell tumor of the rib.

We present a rare case of perivascular epithelioid cell tumor (PEComa) in the right 6th rib of a 28-year-old man. A plain computed tomography scan showed a round osteolytic lesion in the right 6th rib. The resected tissue contained a globular-shaped, soft tumor. Histologically, the tumor was rich in vasculature and exclusively composed of perivascular epithelioid cells with clear cytoplasm. Immunohistochemically, the tumor expressed diffusely a melanocyte marker, human melanoma black-45, and focally a myogenic marker, alpha-smooth muscle actin, but not an epithelial marker, AE1/AE3. Fontana-Masson-positive melanin pigments were present and c-kit receptor tyrosine kinase (CD117), involved in the development of melanocytes but not myogenic cells, was expressed in tumor cells. These findings indicate that the tumor is PEComa with some differentiation into melanocytes. Notably, owing to the unique location of the occurrence, the tumor occupied bone marrow tissues of the rib, resulting that the tumor has the potential for hematogenous metastasis. In spite of the lack of cells with severe atypia, necrosis, and numerous mitoses, tumor cells invaded into surrounding tissues and overexpressed cyclin D1. To the best of our knowledge, this is the first case report of PEComa arising from the rib with the signs of malignant potential.