Efficacy and safety of fibrin sealant patch in the treatment of air leakage in thoracic surgery.

AIM: Air leakage represents a major problem in lung surgery. Absorbable fibrin sealant patch (AFSP), a collagen sponge coated with human fibrinogen and thrombin, can be used as an adjunct to primary stapling or suturing. This study compared the efficacy of AFSP with manual suturing after primary stapling. METHODS: This was a prospective, multicenter, randomized study. Patients undergoing lobectomy, bilobectomy, anatomical segmentectomy for lung cancer or wedge resection for pulmonary metastasis with air leakage grade 1 or 2 according to Macchiarini scale after stapler suture were randomized to receive AFSP or standard surgical treatment (ST). The primary endpoint was the reduction of intraoperative air leakage intensity. Duration of postoperative air leakage and number of days until removal of last chest drain were secondary endpoints. Safety was recorded for all patients. RESULTS: A total of 346 patients were enrolled in 14 centres, 179 of whom received AFSP and 167 ST. Intraoperative air leak intensity was reduced in 90.5% of AFSP patients and 82% of ST patients (P=0.03). A significant reduction in postoperative air leakage duration was observed in the AFSP group (P=0.0437). The median number of days until removal of last drainage was 6 (3-37) in the AFSP group and 7 (2-27) in the ST (P=0.38). Occurrence of adverse events was comparable in both groups. CONCLUSION: AFSP was more efficacious than standard ST as an adjunct to primary stapling in reducing intraoperative air leakage intensity and duration of postoperative air leakage in patients undergoing pulmonary surgery. AFSP was well tolerated.

KRAS G12C mutation and risk of disease recurrence in stage I surgically resected lung adenocarcinoma.

KRAS G12C mutations are found in about 12-13% of LUAD samples and it is unclear whether they are associated with worse survival outcomes in resected, stage I LUAD. We assessed whether KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours and to KRAS wild-type tumours in a cohort of resected, stage I LUAD (IRE cohort). We then leveraged on publicly available datasets (TCGA-LUAD, MSK-LUAD604) to further test the hypothesis in external cohorts. In the stage I IRE cohort we found a significant association between the KRAS-G12C mutation and worse DFS in multivariable analysis (HR: 2.47). In the TCGA-LUAD stage I cohort we did not find statistically significant associations between the KRAS-G12C mutation and DFS. In the MSK-LUAD604 stage I cohort we found that KRAS-G12C mutated tumours had worse RFS when compared to KRAS-nonG12C mutated tumours in univariable analysis (HR 3.5). In the pooled stage I cohort we found that KRAS-G12C mutated tumours had worse DFS when compared to KRAS-nonG12C mutated tumours (HR 2.6), to KRAS wild-type tumours (HR 1.6) and to any other tumours (HR 1.8); in multivariable analysis, the KRAS-G12C mutation was associated with worse DFS (HR 1.61). Our results suggest that patients with resected, stage I LUAD with a KRAS-G12C mutation may have inferior survival outcomes..

Tracheotomy-related posterior tracheal wall rupture, trans-tracheal repair.

Laceration of the membranous part of the tracheo-bronchial tree is a rare complication that can occur after single lumen intubation, double-lumen intubation, percutaneous and surgical tracheotomy. The case of a 76-year-old male is presented in whom a posterior tracheal wall laceration, related to tracheotomy, was diagnosed and immediately treated at the end of a head and neck operation. A 6 cm long laceration started 1.5 cm below the tracheotomy level and ended 2 cm above the carina. The tear was closed from distal to proximal area via the tracheotomy opening with PDS 4/0 interrupted sutures using a thoracoscopic needle-holder. This original surgical technique is described in detail. In tracheotomy related tears, the fact that an opening in the trachea already exists and that the lesion rarely extends beyond the carina, should guide the surgeon to make every effort to repair the laceration through this already existing access.

The Third Italian Consensus Conference for Malignant Pleural Mesothelioma: State of the art and recommendations.

Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.

Familial pleural malignant mesothelioma: clustering in three sisters and one cousin.

Malignant mesothelioma is associated with asbestos, yet its occurrence in genetically-related individuals suggests a role of host predisposition. We have identified a cluster of pleural malignant mesothelioma in three sisters and one cousin (male). The women had worked in the same confectionery shop as pastry cooks and/or pastry shop assistants; the use of an asbestos-insulated oven was the putative source of exposure. The man had occupational exposure as a heating system installation worker. The family history reported malignant cancers in first-degree (larynx, brother; pleura and lung, mother), second-degree (lung, aunt and uncle) and third-degree (lung, cousin) relatives. The study reveals the potential existence of the mesothelioma risk among pastry cooks and highlights the fact that inherited factors may be involved in the development of this tumour.

Chest wall invasion in non-small cell lung carcinoma: a rationale for en bloc resection.

OBJECTIVE: The choice of surgical approach to non-small cell lung cancer invading the chest wall, extrapleural resection versus en bloc chest wall resection, is much more related to the experience of the surgeon than to objective criteria. The aim of the present study is to help to establish a rationale for en bloc chest wall resection in lung cancer invading the chest wall. METHODS: From January 1990 to June 1999, of 1855 patients having major pulmonary resections for non-small cell lung carcinoma, 104 (5.6%) patients with neoplasms involving the chest wall underwent en bloc chest wall and lung resection plus radical mediastinal lymphadenectomy. RESULTS: All patients underwent complete resection with microscopically disease-free tissue margins. Depth of invasion was into the parietal pleura only in 28 (26.92%), into the pleura and soft tissue in 36 (34.62%), and into the pleura, soft tissue, and bone in 40 (38.46%). No operative mortality was reported. Follow-up was completed in 96 patients. One patient had a local recurrence. The overall 5-year estimated survival was 61.4%. Survival in the subsets T3 N0 and T3 N2 were, respectively, 67.3% and 17.9% (P =.007). The 5-year survival was 79.1% in involvement of parietal pleura only and 54.0% in involvement of soft tissue with or without bone invasion (P =.014). Five-year survival was 53.0% in adenocarcinoma versus 71.8% in squamous cell carcinoma (P =.329) and 74.1% in patients who did undergo radiation therapy versus 46.7% in patients who did not undergo radiation therapy (P =.023). CONCLUSIONS: En bloc resection of the chest wall and lung is the procedure of choice to obtain complete resection in lung carcinoma invading the chest wall. Survival is highly dependent on the completeness of resection, nodal involvement, and depth of chest wall invasion.

Computed tomography for the evaluation of intrathoracic invasion by lung cancer.

We conducted computed tomographic examinations of the chest in 171 patients with lung cancer whose disease was subsequently surgically staged; routine mediastinal exploration was undertaken in all patients undergoing thoracotomy (151), and in 20 patients only anterior mediastinotomy or mediastinoscopy was performed. We have considered three groups of patients: In Group I (including all 171 patients) mediastinal lymph nodes were evaluated for metastatic involvement; nodes were considered diseased when greater than 1 cm. Sensitivity, specificity, and accuracy were 95%, 83%, and 89%. Among these 171 patients, 34 (Group II) had a central tumor otherwise considered operable, which was shown on plain roentgenograms to be in contact with the mediastinum; infiltration of hilar and mediastinal vessels and of mediastinal tissues was investigated preoperatively with computed tomography and then ascertained at thoracotomy. Sensitivity, specificity, and accuracy were 68%, 72% and 70%. Twenty-seven patients (Group III) had a peripheral tumor abutting the pleural surface and suspected to invade the parietal pleura and chest wall; patients with evident bone infiltration were excluded. Sensitivity, specificity, and accuracy of computed tomography were 50%, 90%, and 65%.

Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients.

The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC.

Localized (solitary) fibrous tumors of the pleura: an analysis of 55 patients.

BACKGROUND: Localized (solitary) fibrous tumors (LFTPs) of the pleura are rare, slow-growing neoplasms thought to originate from submesothelial connective tissue. The aim of this article is to present 55 new cases of LFTP, and to discuss the treatment of choice and the clinical behavior of such neoplasms. METHODS: From July 1990 to November 1999, 55 patients (32 male, 23 female) with an LFTP were surgically treated at our Institution. Neoplasms were considered to be malignant if one or more of the following histologic features were present: high cellularity with crowding and overlapping of nuclei; high mitotic activity; or mild, moderate, or marked pleomorphism. RESULTS: No operative mortality was reported. Forty-eight of the cases arose from the visceral pleura and seven arose from the parietal pleura. A local removal of the neoplasm with free surgical margins was accomplished by video-assisted thoracic surgery in 39 patients and by standard thoracotomy in 10 patients. Four patients underwent formal lung resections, 1 had thymectomy, and 1 had en bloc chest wall resection. Four malignant variants were identified. One patient developed local recurrence and underwent redo surgery with chest wall resection. One patient died of unrelated disease. The remaining patients are alive and disease free at a median follow-up of 53.2 months. CONCLUSIONS: LFTPs show a benign outcome in most of the cases. Video-assisted thoracic surgery, with intraoperative assessment of the surgical margins, represents the treatment of choice.

Videothoracoscopic treatment of primary spontaneous pneumothorax: a 6-year experience.

BACKGROUND: Timing and surgical approach in the treatment of primary spontaneous pneumothorax (PSP) are not well defined. The objective of this study is to propose a treatment protocol by videothoracoscopy (VATS) in PSP. METHODS: From July 1992 to May 1998, 432 patients underwent VATS treatment of PSP. Indications were: recurrent ipsilateral pneumothorax: 322 cases; persistent air leak following a first episode: 93 patients; recurrence following VATS: 16 cases; recurrence following thoracotomy: 1 patient. Vanderschueren's classification was used for staging. Surgical indications were: stages I and II, subtotal pleurectomy or talc poudrage; stages III and IV, stapling or ligation of the bullae and subtotal pleurectomy or talc poudrage. Differences in recurrence rates were calculated to compare the specific procedures. RESULTS: No postoperative deaths occurred. Complication rate was 4.16%. Conversion rate was 2.3%. Mean follow-up was 38 months (2 to 72 months). Overall recurrence rate was 4.4%. Specific recurrence rates following stapling and talc poudrage were, respectively, 1.27% and 1.79%. Talc poudrage and stapling of the bullae are respectively superior to subtotal pleurectomy (p < 0.0001) and ligation (p < 0.0001). CONCLUSIONS: Stapling of the bullae and talc poudrage by VATS represent the treatment of choice of PSP.

Recurrences following videothoracoscopic treatment of primary spontaneous pneumothorax: the role of redo-videothoracoscopy.

OBJECTIVE: There is very little experience regarding recurrences following videothoracoscopic (VATS) treatment of primary spontaneous pneumothorax. We report our experience with 19 patients who underwent redo-VATS to evaluate the feasibility of such surgical approach. METHODS: From July 1, 1992 to September 1, 2000, out of 2136 VATS procedures performed at our institution, 597 patients (27.94%) underwent VATS treatment of primary spontaneous pneumothorax with a recurrence rate of 3.85% (23 cases). Primary VATS treatment in these patients was: talc poudrage, three cases; subtotal pleurectomy, three cases; ligation of the bullae + subtotal pleurectomy, 12 cases; stapling of the bullae + subtotal pleurectomy, two cases; ligation of the bullae + talc poudrage, one case; stapling of the bullae + talc poudrage, one case. Treatment of the 23 recurrences included: 15 redo-VATS, four standard thoracotomy, three pleural drainage, one bed rest. Four additional redo-VATS were also performed in four patients operated on in different institutions. Redo-VATS showed residual bullae in nine cases and a minimal leaking area in one patient; in the remaining nine patients no lesion was found. Redo-VATS treatment was: stapling of the bullae + talc poudrage in nine patients; suture of the leaking area with a no-knife stapler + talc poudrage in one patient; isolated talc poudrage in the remaining nine patients with no-evidence of bullae or blebs. RESULTS: No mortality was reported; no major complications occurred. The conversion rate in the group of redo-VATS was 5.2% (one patient). At a mean follow-up of 32 months no patient showed recurrent pneumothorax. CONCLUSIONS: In the light of our initial experience, redo-VATS seems to be a promising tool for the surgical therapy of recurrences following VATS treatment of primary spontaneous pneumothorax.

Long-term follow-up of video-assisted talc pleurodesis in malignant recurrent pleural effusions.

OBJECTIVE: Recurrent pleural effusion is a common condition and often presents a challenge for treatment. The aim of this report is to evaluate the long-term follow-up of thoracoscopic management of malignant recurrent pleural effusions. METHODS: From July 1st, 1992 to February 28th, 2001, out of 2311 VATS procedures performed at our Institution, 690 patients (29.85%) underwent videothoracoscopy (VATS) for recurrent pleural effusion. Of these 611 (88.55%) were treated for a malignant pleural effusion. There were 374 male and 237 female, with a mean age of 61.2 years. In all patients VATS was performed under general anaesthesia. The pleural effusion was carefully aspirated; fibrinous adhesions were taken down while dense fibrous adhesions were selectively divided; some limited decortications were also performed. Multiple pleural biopsies were always performed. Pleurodesis was performed with 5 g of sterile purified talc insufflated through a talc atomizer. One chest tube was left in situ for 3-5 days. RESULTS: Operative mortality was 0.81% (five cases). Postoperative complications occurred in 19 cases (3.1%). Specific histologic diagnosis was obtained in all patients. Follow-up was available for 602 patients (98.5%). After a median follow-up of 64 months (range 5-105 months), talc pleurodesis was successful in controlling recurrence of effusion in 92.7% (558 out of 602) of patients. The success rate did not show any statistically significant difference between patients who underwent postoperative adjuvant therapy and patients who did not. In two patients with failure of talc pleurodesis a redo-VATS was performed. CONCLUSIONS: VATS represents the method of choice for both diagnosis and treatment of malignant recurrent pleural effusions. Talc poudrage is safe and effective in obtaining pleurodesis.

The combination of carboplatin and weekly paclitaxel: a safe and active regimen in advanced non small-cell lung cancer patients. A phase I-II study.

The combination of carboplatin and paclitaxel given every three weeks is a tolerated and reasonably active regimen in advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the maximum tolerated dose (MTD) of a fixed dose of carboplatin with an area under the curve (AUC) of 6 and escalating doses of weekly paclitaxel with an initial dose of 50 mg/m2 with 10 mg/m2 increments at each level in untreated NSCLC patients (phase I study). The study continued with a phase II study. Thirty patients entered the phase I study. The MTD was: carboplatin AUC = 6 on days 1 and 28 plus paclitaxel 100 mg/m2 (1 hour) on days 1, 8,15, 28. The dose-limiting toxicity (DLT) was severe neutropenia and cardiological toxicity. Subsequently, 42 patients entered the phase II study with the same treatment schedule. The 2-drug combination was globally well tolerated. The overall response rate (RR) was 42% [CI 95%: 26.3-57.7], stable disease (SD) 29% and progression (PD) 29%. The median duration of response was 8.0 mos (range: 1.0-19.0). The median time to progression was 8.0 mos (range: 7.0-19.0) and the median survival was 14.0 months (range: 9.0-19.0). The association of carboplatin AUC = 6 and weekly paclitaxel 100 mg/m2 proved to be manageable, active and extremely safe even in elderly patients (one third of all patients in our cohort). The survival results were interesting: the median survival time was 14 months (9-19 months) and the 1- and 2-year survival was 59% and 16%, respectively.

Malignant mesothelioma in Rome, Italy 1980-1995. A retrospective study of 79 patients.

AIM AND BACKGROUND: To evaluate the characteristics of a case-series of 79 malignant mesothelioma patients collected from the main teaching hospital of Rome, Italy, and other local clinics of Latium Region and to assess the role of asbestos exposure, since previous studies on the occurrence of the disease in this area were lacking. METHODS: The study included cytohistologically diagnosed malignant mesothelioma (71 pleural, 7 peritoneal, and 1 testicular tunica vaginalis) detected or referred for consultation during the period 1980-1995. Information regarding occupational and/or nonoccupational exposures was derived from clinical records and interviews, when available. RESULTS: Patients were resident in Rome and other towns of Latium; a few were from other parts of central and southern Italy. Exposure to asbestos was assessed for 45.5% of patients, another 45.5% had unknown exposure, and for the remaining 9% such information was lacking. Occupational exposure occurred in 53% of men for whom information was available and nonoccupational exposure occurred in 20% of women. The study identified two clusters of cases from an asbestos-cement plant and a facility where asbestos was ubiquitous. Furthermore, most exposed subjects reported occupations in the construction industry, which is particularly active in the Latium Region; others were railroad workers, naval mechanics and navy personnel, bakers, explosive workers and car mechanics. A few patients reported indoor exposure to asbestos at home and/or in the workplace. CONCLUSIONS: The study confirmed that mesothelioma risk is present in several job titles of the construction industry, and it is no longer confined to workers employed in the manufacture or application of asbestos products. The occurrence of malignant mesothelioma in patients with unexpected occupational and nonoccupational exposures indicates the need for further investigation on previously underestimated exposures.

Cytodiagnosis of a primary non-Hodgkin's lymphoma of bone.

We report fine-needle aspiration cytology and histologic findings of a primary non-Hodgkin's lymphoma of bone involving the rib and iliac bones. Smears contained abnormal lymphoid cells and abundant lymphoglandular bodies, suggesting a malignant lymphoproliferative disease. However, histologic sections showed nests of tumor cells with extensive cytoplasmic clearing surrounded by sclerosis, thus mimicking a carcinoma. Clinical data, radiographic findings, and cytohistological correlation led to a final diagnosis of primary non-Hodgkin's lymphoma of the bone, confirmed by immunopositive staining for leukocyte common antigen CD45 and B-cell associated antigen CD20. It is concluded that finding numerous lymphoglandular bodies in bone tumor specimens allows an accurate diagnosis of lymphoid tissue. The rarity of bone lymphoma and the misleading histologic features can cause considerable difficulty in diagnosing this entity. The importance of identifying lymphoglandular bodies and the appropriate use of immunochemistry are emphasized.

Concomitant malignant mesothelioma of the pleura, peritoneum, and tunica vaginalis testis.

We describe the cytohistological, immunohistochemical and ultrastructural findings in a 55-yr-old-man with history of asbestos exposure and diffuse malignant mesothelioma (DMM) of the pleura, peritoneum, and tunica vaginalis presenting with chest pain and scrotal swelling. Pleural fine-needle aspiration (FNA) revealed mesenchymal elements and spindle-shaped epithelial-like cells, while biopsy showed pure sarcomatous tumor invading lung parenchymal. In both samples tumor cells coexpressed cytokeratin and vimentin. Peritoneal and hydrocele effusions contained aggregates of malignant mesothelial cells. Electron microscopy showed intermediate filaments, rare desmosomes and sparse microvilli. Morphological findings were consistent with a DMM, with a biphasic pattern in the pleura and an epithelial one in the peritoneum and tunica vaginalis. Although the possibility of a multicentric origin cannot be ruled out, clinical chronologic sequence suggests that the pleura was the primary involved site, followed by spread to peritoneum and tunica vaginalis.

Chondroblastoma of the rib presenting as an intrathoracic mass. Report of a case with fine needle aspiration biopsy, immunocytochemistry and electron microscopy.

We describe an unusual case of chondroblastoma of the rib, initially presenting as a mediastinal mass eroding a vertebra, in which the preoperative diagnosis was made by fine needle aspiration (FNA) cytology and confirmed by histology and electron microscopy of the surgical specimen. Cytologic study of the smears revealed osteoclastlike giant cells and dishesive, mononucleate tumor cells; sections of the paraffin-embedded, aspirated material showed the chondroid matrix and typical chicken wire calcific deposits. Supporting diagnostic evidence was provided by immunohistochemical demonstration of S-100 protein. Unusual features were the presence of intranuclear pseudoinclusions and cytoplasmic granular deposits, which proved to contain iron on histochemical staining, ultrastructural morphology and x-ray analysis. This case emphasizes the value of FNA cytology in providing a correct diagnosis of chondroblastoma as well as the utility of embedding the aspirated material for histologic, immunohistochemical and ultrastructural studies.

Platelet-derived growth factor receptor immunoreactivity in mesothelioma and nonneoplastic mesothelial cells in serous effusions.

Expression of the platelet-derived growth factor receptor (PDGFR) was detected by immunocytochemistry in normal and malignant mesothelial cells from 14 benign effusions and 22 mesotheliomas. Two well-characterized antireceptor monoclonal antibodies to the PDGFR alpha-subunit (PR292) and beta-subunit (PR7212) were used. PDGFR alpha-subunit outlined cell membranes intensely in nonneoplastic mesothelial cells, whereas it was focal in mesothelioma and limited to a few cases only. PDGFR beta-subunit was weakly expressed in the cytoplasm of normal mesothelium; in contrast, malignant mesothelial cells showed strong cytoplasmic staining. Our results show that normal mesothelium may be responsive to PDGF by the predominant expression of PDGFR-alpha and less by PDGFR-beta and indicate the presence of growth-stimulation loops in mesothelioma through PDGF/PDGFR-beta interaction. Also, scattered staining for the PDGFR alpha-subunit suggests that a PDGF-A chain/PDGFR-alpha interaction may also be active in mesothelioma cells growing in suspension.

[Surgical therapy of locally advanced non-small cell lung carcinoma]. / La terapia chirurgica del carcinoma del polmone non-microcitoma localmente avanzato.

Experience during the past 10 years has shown up different opinions on the surgical treatment of patients with stage III non-small cell lung cancer. In the light of high resectability and survival rates (respectively 80.8% and 40% at 2 years in the experience of the Southwest Oncology Group) produced with neoadjuvant therapy (followed by surgery) it appears to be an appealing therapeutic option. Until recently, there have been no large prospective randomized phase III trials to answer the question of whether neoadjuvant therapy is superior to other treatment modalities (surgical resection alone; non-surgical treatment).

Protumorigenic effects of mir-145 loss in malignant pleural mesothelioma.

We identified a discrete number of microRNAs differentially expressed in benign or malignant mesothelial tissues. We focused on mir-145 whose levels were significantly downregulated in malignant mesothelial tissues and malignant pleural mesothelioma (MPM) cell lines as compared to benign tissues (pleura, peritoneum or cysts). We show that promoter hyper-methylation caused very low levels in MPM cell lines and specimens. Treatment of MPM cell lines with mir-145 agonists negatively modulated some protumorigenic properties of MPM cells, such as clonogenicity, cell migration and resistance to pemetrexed treatment. The main effector mechanism of the clonogenic death induced by mir-145 was that of accelerated senescence. We found that mir-145 targeted OCT4 via specific binding to its 3'-UTR. Increased intracellular levels of mir-145 decreased the levels of OCT4 and its target gene ZEB1, thereby counteracting the increase of OCT4 induced by pemetrexed treatment which is known to favor the development of chemoresistant cells. In line with this, reintroduction of OCT4 into mimic-145 treated cells counteracted the effects on clonogenicity and replicative senescence. This further supports the relevance of the mir-145-OCT4 interaction for the survival of MPM cells. The potential use of mir-145 expression levels to classify benign vs malignant mesothelial tissues and the differences between pemetrexed-induced senescence and that induced by the re-expression of mir-145 are discussed.