Carcinomatous Pleuritis Research Articles

Cyclin-dependent kinase 4 upregulation mediates acquired resistance of dabrafenib plus trametinib in BRAF V600E-mutated lung cancer.

BackgroundCombination therapy with the B-Raf inhibitor, dabrafenib, and the MEK inhibitor, trametinib (DT) is commonly used to treat patients with B-Raf proto-oncogene, serine/threonine kinase V600E (BRAF V600E)-mutated non-small cell lung cancer (NSCLC). However, the mechanisms through which cancer develops DT resistance are unclear. Here, we investigated new mechanisms underlying acquired DT-resistant NSCLC with the BRAF V600E mutation.MethodsWe compared genomic signatures before and after DT treatment in patients with NSCLC.ResultsTwo of four patients treated with DT developed carcinomatous pleuritis within 3 months. Target DNA sequencing and quantitative polymerase chain reaction (PCR) analyses revealed the increased expression level of cyclin-dependent kinase 4 (CDK4). We also found prominent protein expression of CDK4 after DT treatment. Induction of CDK4 expression in a cell line derived from a patient with the BRAF V600E mutation resulted in partial resistance to dabrafenib.ConclusionsOur findings suggest a possible relationship between CDK4 upregulation and acquired resistance to DT therapy.

Radical aggressive treatment among non-small cell lung cancer patients with malignant pleural effusion without extra-thoracic disease.

Malignant pleural effusion (MPE) is an indicator of advanced disease (stage M1a) in patients with non-small cell lung cancer (NSCLC). Typically, these patients are candidates for palliative treatment. There is a lack of evidence about the radical surgical treatment in carcinomatous pleuritis with massive effusion. Here, we present data from a specific subset of patients with MPE treated with systemic therapy and aggressive surgical therapy. M1a NSCLC adenocarcinoma patients with MPE and without extra-thoracic disease were included. After receiving systemic therapy, all patients underwent surgical treatment, which included pneumonectomy or lobectomy, plus mediastinal dissection. Following surgery, patients received radiotherapy to thoracic wall and mediastinum. A total of six patients were analyzed. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status ≤1, two patients harbored EGFR mutation and were treated with tyrosine kinase inhibitors (TKIs), the other four patients were treated with pemetrexed and platin as first-line treatment. Following systemic therapy, two patients had a pneumonectomy, four patients had a lobectomy plus pleurectomy performed. All patients continued with maintenance systemic therapy, and achieved complete responses, according to RECIST 1.1 criteria. The media progression-free survival (PFS) time was 15.9 months (95% CI: 15.6-55.5 months). At the last follow-up, all patients were still alive, with 4 of them without signs of macroscopic tumoral activity. The median overall survival (OS) was not reached. NSCLC patients with MPE without extra-thoracic disease could benefit from an aggressive surgical approach following standard of care systemic therapy. However, considering the low sample size of this study and the relatively low incidence of MPE without extra-thoracic disease, further prospective multi-center studies are necessary to evaluate aggressive surgery as a therapeutic option.

O3-9-4 - Phase II study of carboplatin/pemetrexed/bevacizumab for non-squamous NSCLC with carcinomatous pleuritis (NEJ013A)

O3-9-4 - Phase II study of carboplatin/pemetrexed/bevacizumab for non-squamous NSCLC with carcinomatous pleuritis (NEJ013A)

Tongue squamous cell carcinoma producing both parathyroid hormone-related protein and granulocyte colony-stimulating factor: a case report and literature review

BackgroundParaneoplastic syndrome generally results from tumor-derived hormones or peptides that cause metabolic derangements. Common metabolic conditions include hyponatremia, hypercalcemia, hypoglycemia, and Cushing’s syndrome. Herein, we report a very rare case of tongue carcinoma presenting with leukocytosis and hypercalcemia.Case presentationA 57-year-old man was admitted to our hospital with tongue squamous cell carcinoma (cT4aN0M0, stage IV). He underwent radical resection following preoperative chemoradiotherapy, but locoregional recurrence was detected 2 months after surgery. He presented with marked leukocytosis and hypercalcemia with elevated serum levels of granulocyte colony-stimulating factor (G-CSF) and parathyroid hormone-related protein (PTHrP). He was therefore managed with intravenous fluids, furosemide, prednisolone, elcatonin, and pamidronate. However, the patient died 1 month later of carcinomatous pleuritis following distant metastasis to the lung. Immunohistochemical analyses of the resected specimens revealed positive staining for PTHrP and G-CSF in the cancer cells.ConclusionsIn this case, it was considered that tumor-derived G-CSF and PTHrP caused leukocytosis and hypercalcemia.

Experimental validation of talc pleurodesis for carcinomatous pleuritis in an animal model.

This study was performed to evaluate the change of pleural cavity by talc pleurodesis for carcinomatous pleuritis in an animal model. Models of malignant pleuritis were produced by an intra-venous injection of lung adenocarcinoma cells to male BALB/c nude mice at 6weeks of age. Two weeks after the injection, either talc or saline was injected into the left thoracic cavity and the mice were further observed for 4weeks. Six weeks after the injection, they were killed and the occurrence of lung cancer, amount of pleural effusion, and histological change of the pleural cavity were examined and compared between the two groups with or without talc administration. Talc administration caused a significant reduction in pleural effusion with no increase of pleural adhesion. Talc administration resulted in marked pleural thickening compared to saline treatment. The vascular architecture and its area did not differ between the two groups. Talc pleurodesis to reduce pleural effusion is valid for carcinomatous pleuritis, potentially through an acceleration of pleural thickening.

Morphologische Diagnostik maligner Pleuramesotheliome

The World Health Organization (WHO) classification differentiates between pleural tumors of mesothelial and mesenchymal origin as well as lymphoproliferative disorders, with malignant mesotheliomas forming the most common pleural primary tumor. Histologically, epithelioid (40-60 %), sarcomatoid (20-40 %), and biphasic mesotheliomas (20-40 %) are distinguished. The certain morphological diagnosis of a malignant pleural mesothelioma requires the establishment of mesothelial differentiation by means of an appropriate panel of antibodies to exclude pleural dissemination of a pulmonary or extrapulmonary epithelial malignancy and also requires the establishment of at least focal invasive growth to distinguish from reactive mesothelial proliferation. The exclusion of a malignant pleural mesothelioma may induce further differential diagnostic considerations, e. g. concerning the assignment to a certain primary tumor after the establishment of carcinomatous pleuritis.

Role of surgery in multi-modality treatment for carcinomatous pleuritis in patients with non-small cell lung cancer.

To evaluate the role of surgery in the treatment of the patients with non-small cell lung cancer with pleural dissemination. The clinical records of 25 patients (mean age 69 years) diagnosed with carcinomatous pleuritis during a thoracotomy by pathological examination and followed by surgery between 1994 and 2012 were reviewed. The treatment modality, including surgery, the clinicopathologic characteristics and 5-year survival were analyzed. There were 16 adenocarcinomas, 6 squamous cell carcinomas and 3 large cell carcinomas. Surgery included resection of the main tumor by partial resection in 10 cases, segmentectomy in 2 cases, lobar resection in 12 cases and bilobectomy in 1 case. Intrathoracic irrigation was performed in 20 cases. The pathological N status was N0/N1/N2/Nx: 10/6/7/2. Fifteen patients received adjuvant therapy. The overall 5-year survival rate was 22.2 %. The 5-year survival rates of the N0, N1 and N2 groups were 36.0, 16.7 and 14.3 %, respectively (p = 0.0068). Nine patients lived more than 3 years including 5 in N0, 3 in N1 and 1 in N2. Surgery should not be excluded from the multi-modality treatment of patients with carcinomatous pleuritis because there are some patients who could benefit from surgery especially if they are in N0 status.

Surgical management of locally advanced lung cancer.

Majority of cases of lung cancer are detected at an advanced stage; such patients are usually treated with chemotherapy and radiotherapy, and the prognosis is frequently poor. Surgical resection remains the only reliable curative method for the treatment of lung cancer, and combined resection of the primary tumor and involved neighboring structures is performed when possible in patients with locally advanced disease. In the TNM classification, tumors with direct extrapulmonary extension are subdivided based on the anatomic extent of disease and its potential for surgical treatment: T3 lesions with limited, circumscribed extension are thought to be potentially surgically resectable, whereas T4 tumors with extensive extension are considered unresectable. Although surgical treatment for T3 lesions is generally accepted, the outcome is frequently not satisfactory. On the other hand, advanced surgical techniques are now being applied for T4 lesions due to improvements in surgery and anesthesiology and progress in combined treatment modalities. In the present staging, T4N0-1M0 lesions are categorized as stage IIIA disease, and T4 tumors without mediastinal nodal metastasis are now considered to be potentially curable if complete resection is possible. This article reviews the modern surgical management of patients with lung cancer invading neighboring structures, including the chest wall, superior sulcus, diaphragm, tracheal carina, left atrium, superior vena cava, aorta and vertebrae. Furthermore, the surgical treatment of carcinomatous pleuritis, which was categorized as T4 disease in the previous TNM classification, is also assessed, and the role of surgical resection in cases of locally advanced lung cancer is discussed.

肺葉切除後に肺内転移が認められた犬に対し外科切除および補助的化学療法を行った1例

A 9-year-old neutered female Miniature Dachshund had undergone lobectomy of the left frontal lobe for lung carcinoma followed by nine post-operative doses of carboplatin chemotherapy(250 mg/m2, every 3weeks). The dog was referred to the Japan Animal Referral Medical Center (Nagoya), because of lung masses in the opposite right middle and posterior lobes. Whole body contrast-enhanced computed tomography(CT)was performed and revealed lung solitary tumors in the relevant areas. No abnormal findings were observed in other lobes or intrathoracic lymph nodes. Since the possibility of metastatic lesions of lung carcinoma incompletely removed in the previous surgery was considered, we performed CT again on day 45 for evaluation of the new tumor progression. The size of both tumors increased, and right middle and posterior lung lobectomies were carried out on day 53. There were no adhesive lesions around the tumors, carcinomatous pleuritis, pleural fluid or hilar lymphadenopathy. While histopathology revealed high-grade lung adenocarcinoma with numerous mitoses, there was no evidence of intravascular invasion, suggesting complete resection. A tentative diagnosis of metastatic lung tumor(T2N0M1)was made. Adjuvant chemotherapy with carboplatin(250 mg/m2, for every 3 weeks)and piroxicam(0.3 mg/kg/3 days)was also given starting on day 21, and no evidence of recurrent lesions was observed on day 726 with a good health condition maintained. From these results, it is suggested that aggressive surgery plus adjuvant chemotherapy can be appropriate treatments for metastatic lung carcinoma.

EGFR-TKI'ya tepki sonrası akciğer adenokarsinomadan peritoneal relaps

kinase inhibitors (EGFR-TKIs) for EGFR-mutated elderly non-small cell lung cancer (NSCLC) patients has been reported (1,2). It is supposed that EGFR-TKIs are increasingly prescribed for them. In NSCLC patients, metastases to meningeal as well as peritoneal space are rare (3,4). However, carcinomatous meningitis, which attracts attention as a recurrence site of the patients who received EGFR-TKIs), is recently a devastating event occurring in NSCLC patients (5). For them, the treatment options currently available are very limited, and the prognosis of them remains poor (3,4). Usefulness of EGFR-TKIs for peritoneal carcinomatosis in two chemo-naive NSCLC patients has recently been reported (6,7), but antemortem diagnosis of carcinomatous peritonitis in NSCLC patients is very difficult (4). We experienced three cases with peritoneal relapse from lung adenocarcinoma after a response to EGFR-TKI. Table 1 showed clinical features of the three lung cancer patients with peritoneal recurrence. They were an 83 yearold woman and a 77 year-old men, and a 72 year-old woman. All of them were non-smokers, and diagnosed as having lung adenocarcinoma pathologically, and they had a point mutation in exon 21 (L858R), respectively. At the time of initial diagnosis, these two women had carcinomatous pleuritis. Gefitinib or erlotinib was prescribed as first line chemotherapy in each patient. All of them responded to the therapy, and progressive free survival was 31, 9, and 8 months, respectively. After these response periods, they complained distension of the abdomen. Abdominal CT scan detected ascites, but there found no other recurrent site than peritoneum. Cytological examination of ascites, lung adenocarcinoma was confirmed. Two patients had isolated peritoneal relapse, and one had peritoneal and meningeal relapse (8). They had supportive care only because of their poor performance status.

Ten cases of resected solitary pulmonary metastases arising from gastric cancer.

Because carcinomatous lymphangitis and carcinomatous pleuritis are the usual forms of metastasis associated with gastric cancer, resection of solitary pulmonary metastases arising from gastric cancer is rarely performed. To clarify the characteristics of pulmonary metastases from gastric cancer, we investigated patients who underwent resection of metastatic solitary lung tumors arising from gastric cancer. Between October 2003 and October 2012, 10 patients underwent pulmonary metastasectomy for metastatic gastric cancer at our institution. We retrospectively evaluated features of the primary gastric cancer and the clinicopathological features of the pulmonary metastases in these cases. 70% of the patients had stage II disease. Lymphatic invasion was observed in all cases of primary gastric cancer. The method of pulmonary resection was partial resection in 5 cases, segmentectomy in 1, and lobectomy in 4. On histopathological examination, immunohistochemical staining was negative for thyroid transcription factor-1 and napsin A in all cases. Patients who underwent resection of pulmonary metastases arising from gastric cancer had a good prognosis: the 4-year survival rate was 75%. Carefully chosen patients have a good opportunity to obtain benefits from resection of pulmonary metastases arising from gastric cancer.

Cytoreductive surgery and post-operative heated pleural chemotherapy for the management of pleural surface malignancy

Purpose: We retrospectively analysed the long-term outcomes of cytoreductive surgery and post-operative heated pleural chemotherapy (HPC) for thoracic malignancies with pleural spread. Materials and methods: Between 1987 and 2010, 160 patients were enrolled. There were 101 patients with non-small cell lung cancer (NSCLC), 25 with malignant pleural mesothelioma (MPM), 12 with thymoma, and 22 with tumours metastatic to the lung and pleura. Immediately after intra-thoracic administration of cisplatin or carboplatin, hyperthermia was performed by using an 8.00 MHz radiofrequency capacitive heating device for 1 to 4 courses in each patient. Results: There was no systemic toxicity or treatment-related mortality. Five-year overall survival rates were 37.4% in NSCLC, 15.9% in MPM, 91.7% in thymoma, and 25.8% in metastatic lung tumour. Five-year local relapse-free survival (RFS) rates were 55.2% in NSCLC, 24.4% in MPM, 64.8% in thymoma, and 27.2% in tumours metastatic to the lung and pleura. When 101 NSCLCs were categorised into pleural lavage cytology positive (grade 1: n = 37), limited extent of carcinomatous pleuritis (grade 2: n = 21), and extensive carcinomatous pleuritis (grade 3: n = 43), 5-year overall survival rates were 62.5%, 49.2%, and 13.6%, respectively. The local RFS was significantly better in group 1/2 than in group 3. Conclusions: Although our study has some of the usual weaknesses of a single institution retrospective study, cytoreductive surgery and HPC are feasible and safe. It is suggested that HPC may have a potential role for local control as adjuvant treatment for cytoreductive surgery in patients with minor pleural spread.

Malignant pleural effusion in breast cancer 12 years after mastectomy that was successfully treated with endocrine therapy

Patient: Female, 94Final Diagnosis: Malignant pleural effusionSymptoms: —Medication: —Clinical Procedure: CytologySpecialty: OncologyObjective:Unusual clinical courseBackground:The most common site of postoperative breast cancer recurrence is bone, followed by local relapse, lung, and liver. The majority of relapses occur within the first 3 years after surgery. Pleural recurrences more than 10 years after surgery are rare.Case Report:A 94-year-old woman who had undergone modified radical mastectomy for right breast cancer (invasive ductal carcinoma, pT2, pN1, ER+, PgR+) 12 years earlier presented to our hospital with carcinomatous pleuritis and a chief complaint of dyspnea. Endocrine therapy with oral letrozole was started and the pleural effusion had disappeared 3 months later.Conclusions:Oral endocrine therapy may be effective for the treatment of late recurrence of hormon receptor-positive breast cancer in elderly women.

Clinical Characteristics of Resected T3 Non-small Cell Lung Cancer Characterized by Parietal Pleural Invasion or Chest Wall Invasion

This study investigated the clinicopathological characteristics and the surgical outcome in patients with non-small cell carcinoma (NSCLC) with parietal pleura invasion or chest wall invasion (p3/T3). This study clinicopathologically evaluated 760 patients who had undergone a resection for NSCLC between 1999 and 2008. There were 43 (5.7%) patients with p3/T3 NSCLC. The patients included 37 males and 6 females. The histological types included 23 squamous cell carcinomas, 13 adenocarcinomas, 3 large cell carcinomas, 3 pleomorphic carcinomas, and 1 spindle cell carcinoma. Pneumonectomy was performed in 2 patients, bilobectomy in 1, lobectomy in 31, segmentectomy in 3, and partial resection of the lung in 6. The combined resection regions were parietal pleural in 23, ribs in 16, pericardium in 2, and diaphragm in 2 patients. Major complications included empyema in 1, chylothorax in 1, and postoperative bleeding in 1 patient. The first recurrence sites in 16 patients with recurrent disease were the lung in 5 patients, brain in 3, bone in 2, adrenal gland in 2, skin in 2, liver in 1, mesenterium in 1, mediastinal lymph node in 1, axillary lymph node in 1, and carcinomatous pleuritis in 1. The overall 5-year survival rate after surgery was 50.6%. An en bloc resection for p3/T3 NSCLC provides a modestly favorable prognosis. Local recurrence was observed in a minority of case, and recurrence by distant metastasis was observed in most cases, suggesting a greater need for postoperative chemotherapy.

A case of intractable pneumothorax caused by carcinomatous pleuritis

症例は92歳女性．労作時呼吸困難に対し胸部X線写真が施行され，左気胸の診断にて当科へ紹介となった．胸腔ドレナージによる保存的加療では改善が得られず，手術の予定となった．術前精査での胸部CTにて，左肺上葉に画像診断上原発性肺癌と考えられる結節影が指摘された．その他肺野には気胸の原因となるような病変は指摘されず，手術にて腫瘍を含めた楔状切除を施行した．病理診断にて原発性肺癌と診断され，また，術中所見と合わせすでに癌性胸膜炎を来たしているものと判断された．術後エアリークは消失していたが，術後2日目からエアリークが再発し，最終的に癒着療法を施行した難治性気胸の1例であった．原発性肺癌に併発した気胸についての報告は散見されるが，癌性胸膜炎を来たした段階で気胸の手術が施行された報告はなく，また，癌性胸膜炎により気胸が難治性であった可能性も疑われるため，若干の文献的考察を加え報告する．

Surgery for metastatic pleural extension of non-small-cell lung cancer

Malignant cells in the pleural fluid or pleural metastases are now classified stage IV in lung cancer and alter the treatment. Our purpose was to question the role of surgery in such patients. The clinical records of 4668 patients, who underwent lung cancer surgery, were reviewed. In some, an undiagnosed pleural malignant disease (M1a) was discovered during thoracotomy. When feasible, selected patients underwent complete surgical resection of the primary tumor and pleural nodules. We analyzed the epidemiology, pathology, and prognosis characteristics of that group (study group), as compared with the population undergoing pulmonary resection in a curative attempt (overall population) or exploratory thoracotomy in case of unexpected disseminated carcinomatous pleuritis (control group). The study group included 32 patients (25 males), mean age 59 ± 8.8 years, who underwent pneumonectomy (n = 9) or lobectomy (n = 23), associated with mediastinal lymph nodes dissection and surgical resection of associated pleural nodules. There were 21 adenocarcinomas, seven squamous cell carcinomas, two undifferentiated large cell carcinomas, and two miscellaneous tumors. Pathological node (pN) was: N0 in 10 patients (31.3%), N1 in four (12.5%), and N2 in 18 (56.3%). Five-year survival rate was 16% after resection, and 21% if the resection was a lobectomy. Complete surgical resection of non-small-cell lung cancer (NSCLC) associated with limited metastatic pleural involvement is associated with long-term survival in 16% of the cases. A review of the published data, together with the results of this series, may justify the inclusion of surgery in multimodality treatment of NSCLC patients with metastatic pleural extension.

Thoracoscopy Under Local Anesthesia Diagnosed Carcinomatous Pleuritis in a Case of Recurrent Kidney Cancer 18 Years After Initial Surgery

Thoracoscopy Under Local Anesthesia Diagnosed Carcinomatous Pleuritis in a Case of Recurrent Kidney Cancer 18 Years After Initial Surgery

Predominant Vasogenic Edema in a Patient with Fatal Cerebral Air Embolism

Cerebral air embolism (CAE) is a rare neurologic complication that can occur in patients undergoing various medical procedures or trauma. CAE can sometimes result in death caused by severe brain edema. In spite of these implications, the pathophysiologic mechanisms and radiologic features of fatal CAE remain to be elucidated. In this case report, a patient with carcinomatous pleuritis lost consciousness and developed quadriplegia and had generalized seizures during intrathoracic lavage. Serial computed tomography (CT) revealed the presence of air in intracranial blood vessels following severe brain edema; these are typically observed on the CT scans of patients with fatal CAE. Diffusion-weighted imaging (DWI) of the brain obtained at 24 hours after the onset of CAE revealed scattered cortical gyriform high signal intensity often observed in CAE cases, whereas the apparent diffusion coefficient and T2-weighted imaging revealed diffuse hyperintensity in the subcortical deep white matter, indicating vasogenic edema. Our case showed predominant vasogenic edema rather than cortical ischemic changes in the subcortical deep white matter area. These findings indicate that diffuse subcortical vasogenic edema could be the main cause of mortality in fatal CAE.

Modification of the surgical procedure to enable the complete resection of lung cancer with carcinomatous pleuritis

Carcinomatous pleuritis, accompanied by pleural dissemination or malignant pleural effusion, is listed as one of the factors limiting adequate surgical treatment. It is relatively easy to peel the parietal pleura of the chest wall and mediastinum during a pleuropneumonectomy, but it is quite difficult to peel the parietal pleura of the diaphragm. A pleuropneumonectomy was conducted with the combined resection of the pericardium and all layers of the diaphragm without opening of the peritoneum through a posterolateral subcostal approach. This approach thus made it possible to perform a complete resection of the diaphragm relatively easily in a reliable manner, and also contributed to a more thorough resection of pleural dissemination without a second thoracotomy.

Surgical Resection for Patients With Mucinous Bronchioloalveolar Carcinoma

The clinical features of mucinous bronchioloalveolar carcinoma (BAC) have remained unclear due to the low incidence of this disease. This study investigated the clinicopathological features and the surgical outcome in patients with mucinous BAC. We clinicopathologically evaluated 782 patients who underwent resection for nonsmall cell carcinoma between 1999 and 2008, of whom, 13 (1.6%) demonstrated to have mucinous BAC. The patients with mucinous BAC included six men and seven women. The mean age was 69.1 years (range: 55-78 years). Eight patients (61.5%) had a smoking habit. No patients had any subjective symptoms. The tumour diameter ranged from 1.2 cm to 10 cm. The surgical procedures included 11 lobectomies, and two partial resections of affected lobes. The pathological stage was IA in eight patients, IB in two, IIA in two, and IIIA in one. None of the patients had lymph node metastases or lymphovascular invasion. The overall postoperative 5-year survival rate was 52.5%. The 5-year survival rate according to tumour diameter was 100% in patients with tumours ≤ 3 cm, and 25.1% in patients with tumours > 3 cm. Two patients died due to pulmonary metastases, and one died from carcinomatous pleuritis and pulmonary metastases. Patients with small mucinous BAC (≤ 3 cm) in diameter showed excellent prognosis after surgical resection. However, mucinous BAC > 3 cm in diameter tended to recur with pulmonary metastasis.