Hepatocyte Growth Factor Enhances Antineoplastic Effect of 5-Fluorouracil by Increasing UPP1 Expression in HepG2 Cells.

Aberrant activation of hepatocyte growth factor (HGF) and its receptor c-Met axis promotes tumor growth. Therefore, many clinical trials have been conducted. A phase 3 trial investigating a monoclonal antibody targeting HGF in combination with fluoropyrimidine-based chemotherapy had to be terminated prematurely; however, the reason behind the failure remains poorly defined. In this study, we investigated the influence of HGF on the antineoplastic effects of 5-fluorouracil (5-FU), a fluoropyrimidine, in HepG2 cells. HGF suppressed the proliferative activity of cells concomitantly treated with 5-FU more robustly as compared to that of cells treated with 5-FU alone, and markedly increased the expression of uridine phosphorylase 1 (UPP1). Intracellular concentration of 5-fluorouridine, an initial anabolite of 5-FU catalyzed by UPP1, was increased by HGF. Interestingly, erlotinib enhanced HGF-induced increase in UPP1 mRNA; in contrast, gefitinib suppressed it. Furthermore, erlotinib suppressed HGF-increased phosphorylation of the epidermal growth factor receptor at the Tyr1173 site involved in downregulation of extracellular signal-regulated kinase (Erk) activation, and enhanced the HGF-increased phosphorylation of Erk. Collectively, these findings suggest that inhibition of the HGF/c-Met axis diminishes the effects of fluoropyrimidine through downregulation of UPP1 expression. Therefore, extreme caution must be exercised in terms of patient safety while offering chemotherapy comprising fluoropyrimidine concomitantly with inhibitors of the HGF/c-Met axis.

[Preoperative Spontaneous Regression of Thymoma].

We report a case of preoperative spontaneous regression of thymoma in a 66-year-old woman who presented chest pain. Chest computed tomography revealed a well-defined tumor in the anterior mediastinum. The long axis of the tumor decreased from 25 to 18 mm during 1 month preoperatively. Video-assisted thoracoscopic thymothymectomy was performed for definitive diagnosis and treatment. Histopathologically, the tumor mainly comprised necrotic components with partially viable cells, and was diagnosed as a thymoma. The occlusion of the feeding artery by organized thrombus was found by pathology and it was considered to be the cause of coagulative necrosis.

Fluorodeoxyglucose Positron Emission Tomography Can Provide Useful Information for Differentiating Thymic Epithelial Tumors.

BACKGROUND: We examined the usefulness of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting the World Health Organization (WHO) histologic type and Masaoka stage of thymic epithelial tumors. METHODS: A total of 73 patients with thymic epithelial tumors who underwent preoperative FDG-PET were included. Relationships between the maximum standardized uptake value (SUVmax) and WHO histologic type and the Masaoka stage of the tumor were examined. Differences in SUVmax between the various groups were calculated. To avoid the effect of the tumor size on SUVmax, the ratio of SUVmax to tumor size (SUVmax/T) was also examined. RESULTS: There was a significant relationship between SUVmax and WHO histologic type. SUVmax of high-risk thymomas (types B2 and B3) was significantly higher than that of low-risk thymomas (types A, AB, and B1). SUVmax of thymic carcinomas was also significantly higher than those of the low-risk and high-risk groups. The relationship between the SUVmax/T and WHO histologic type showed more significant results. SUVmax and SUVmax/T showed higher values in patients with advanced Masaoka stage disease than in those with early-stage disease. CONCLUSIONS: FDG-PET can provide useful information for differentiating thymic epithelial tumors. The SUVmax/T is more useful than the SUVmax for differentiating between low-risk and high-risk thymomas.

Unusual cystic hamartomatous lung lesion with clinical manifestation of subpleural bullae in a woman of reproductive age: A case report.

Pulmonary hamartoma is a common benign lung disorder, and most cases show solid nodules. Here, we documented the clinicopathological features of a growing, bulla-like, multilocular hamartomatous lung lesion in a woman of reproductive age. To the best of our knowledge, this disorder has not been reported in the literature to date. An asymptomatic 29-year-old Japanese woman with no significant past medical history was referred to our institution for surgical treatment of a bullous lesion in the right upper lobe because the pulmonary lesion had enlarged to multilocular cysts, including a giant bulla, within 1 year, leading to compression of the right lung. The bullous lesion, which was projected from the apex of the lung via a narrow stalk, showed nonemphysematous, multiloculated tissue. The wall mimicked a bronchiolar structure with ciliated, nonatypical epithelium and layers of nonatypical spindle cells that were positive for smooth muscle markers and sex steroid hormone receptors. No cartilage was included in the lesion. We believe that this may be a novel form of hamartoma. This disorder may be included in a differential diagnosis of subpleural bullous diseases in women of reproductive age.

Radiological features and surgical management of lung abscess directly extending into the chest wall: A case report.

INTRODUCTION AND IMPORTANCE: We presented an extremely rare case of lung abscess following bronchoscopy associated with lung cancer that extended directly into the chest wall. CASE PRESENTATION: A 49-year-old man with adenocarcinoma underwent bronchoscopy. Eight days after the biopsy, the patient presented with chills and anterior chest wall pain. Chest computed tomography (CT) scan revealed a gas-containing lung abscess, measuring 10 cm in the left upper lobe and subcutaneous emphysema. The coronal view of the CT indicated a continuous passage of air from the lung abscess to the subcutaneous emphysema beneath the pectoralis muscle. Surgical debridement of the subcutaneous abscess was performed, resulting in drainage of a large volume of purulent material. We confirmed that the lung abscess had directly extended to the chest wall, leading to a decision to perform segmentectomy of the upper division of the left lung. CLINICAL DISCUSSION: Lung abscess associated with lung cancer is a rare, life-threatening complication, which may lead to significant delays in the commencement of oncological treatment and potentially worsen long-term outcomes. In the present case, surgical findings confirmed a lung abscess extending directly to the chest wall. Surgical therapy is the treatment of choice for this rare condition, providing rapid focus control. Therefore, prompt initiation of surgical therapy is essential when conservative measures prove ineffective. CONCLUSION: Lung abscesses may extend into the chest wall during differential diagnosis of infectious diseases of the chest wall. Successful treatment of this rare condition depends on prompt surgical intervention.

[Parasternal approach for anterior apical lung cancer with invasion of the first rib].

For complete resection of anterior apical invasive lung cancer, it is of clinical significance to select the appropriate surgical approaches based on the anatomic location of the tumor and extent of invasion of adjacent anatomic structures. However, patients with anterior apical lung cancer without vessel invasion are occasionally burdened with unnecessarily excessive surgical invasion. We present 2 cases of anterior apical lung cancer invading the 1st rib but not subclavian vein, who underwent complete resection through the parasternal approach. We also discuss the feasibility of this approach.

A spontaneous reduction in tumor size of a thymic carcinoma: a case report.

BACKGROUND: Spontaneous regression of thymic carcinoma is extremely rare. We report a case of a resected thymic carcinoma with preoperative spontaneous regression in a 67-year-old woman. CASE PRESENTATION: The patient presented with low-grade fever and anterior chest pain. Chest computed tomography (CT) showed a 55 × 43 mm exophytic heterogeneously enhancing mass showing some areas of necrosis. Chest CT done one day preoperatively revealed that the tumor had rapidly shrunk for one month. Surgical resection was performed to obtain a definitive diagnosis and achieve complete resection, yielding a postoperative diagnosis of thymic carcinoma. The patient survived without signs of recurrence for 12 months postoperatively. CONCLUSIONS: Mediastinal tumors with necrosis demonstrating spontaneous regression should include thymic carcinomas in the differential diagnosis.

Intrapulmonary solitary fibrous tumor coexisting with lung adenocarcinomas.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare tumor of mesenchymal origin and accounts for < 2% of all soft tissue masses. Although SFT has been identified in multiple anatomic locations and can grow anywhere in the body, intrapulmonary SFT are rare. CASE PRESENTATION: In this report, we presented a rare case of intrapulmonary solitary fibrous tumor (SFT) coexisting with lung adenocarcinoma in a 74-year-old man. Chest computed tomography showed a well-defined nodule with punctate calcification and measuring 2.3 × 2.1 cm and two ground-grass nodules with solid component. To obtain a definitive diagnosis and achieve complete resection, surgery was performed. The postoperative diagnosis was intrapulmonary SFT coexisting with lung adenocarcinoma. After surgery, he survived for 6 months without any signs of recurrence. CONCLUSION: Complete resection may be the best treatment for intrapulmonary SFT. Careful follow-up of the postoperative course is important, because differentiating between benignity and malignancy is difficult by histologic findings alone.

Primary mucinous adenocarcinoma of the thymus: A case report.

Primary thymic mucinous adenocarcinoma is extremely rare; to our knowledge, only 16 cases have been reported to date. A 68-year-old man presented to a previous hospital due to massive pericardial effusion. Cytological examination of the pericardial effusion revealed the presence of adenocarcinoma, and computed tomography showed an anterior mediastinal mass lesion invading the pericardium. Because systemic examination failed to detect other lesions, except for liver metastasis, mediastinal lymph node swelling, and pleural dissemination, a thoracoscopic biopsy of the mediastinal and pleural tumor was performed. The pathological diagnosis was thymic mucinous adenocarcinoma. Although he received chemotherapy, he died due to cancer 6 months after the biopsy.

Pulmonary torsion after resuscitative thoracotomy: a case report.

We report a rare case of pulmonary torsion after nonpulmonary thoracotomy. A 38-year-old woman with schizophrenia committed suicide by a self-infliction of sharp force into the chest and abdomen. During emergent abdominal damage control surgery, a left-sided resuscitative thoracostomy was also performed due to hemorrhagic shock. Although abnormal shadow was detected on postoperative chest roentgenogram and computed tomography, the diagnosis of pulmonary torsion was delayed. Seven days after initial surgery, pulmonary torsion was diagnosed and managed by left upper lobectomy. To our knowledge, this is the first report of pulmonary torsion after resuscitative thoracotomy.

Recurrent solitary fibrous tumor of the pleura with malignant transformation: a case report.

We report a rare case of recurrent solitary fibrous tumor (SFT) of the pleura with suspicious malignant transformation. A 78-year-old man had undergone prior surgical resection of the primary and recurrent SFT tumors at 11 and 2 years before the current presentation. Although his primary tumor had a round shape and did not show invasive growth, the current recurrent tumor extended through the neural foramen and had an osteoclastic progression into the thoracic spine. A computed tomography (CT) guided needle biopsy was performed and the pathological diagnosis of the tumor was confirmed as the recurrence of SFT. Immunohistochemically, the MIB-1 proliferation index (Ki-67) of the primary tumor and the current tumor was 1.74 and 30.00%, respectively. These clinical and immunohistochemical findings were strongly suspected the malignant transformation of SFT from benign. He was treated with radiotherapy, and a response was observed.

Prognostic Impact of a Novel Tumor Marker and Inflammation Index for Patients With Non-small-cell Lung Cancer.

BACKGROUND/AIM: Different tumor markers and systemic inflammation have been linked with cancer development and poor outcome. We aimed to establish a novel non-invasive prognostic index for patients with resectable non-small cell lung cancer (NSCLC) based on serum carcinoembryonic antigen (CEA) and C-reactive protein (CRP). PATIENTS AND METHODS: Four hundred and sixty-two patients curatively resected for NSCLC between 2008 and 2014 were included. All patients with a follow-up period of less than 5 years were omitted. The geometric mean of the normalized serum CEA and CRP levels was used as a novel tumor marker and inflammation index (TMII). The cut-off value of TMII was determined by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to identify the relative risk factors for survival. RESULTS: ROC curve analysis revealed a TMII cut-off value of 0.46. The group with high TMII displayed more adverse clinical characteristics. Furthermore, compared to patients with low TMII, the group with high TMII had significantly poorer survival. On multivariate analysis, TMII was independently associated with survival. CONCLUSION: We established a novel prognostic index (TMII) based on serum CEA and CRP. Preoperative TMII may predict poor outcomes in patients with NSCLC.

The Prognostic Values of a Novel Preoperative Inflammation-Based Score in Japanese Patients With Non-Small Cell Lung Cancer.

BACKGROUND: Several previous researchers have investigated the prognostic value of the combinations of systemic inflammatory markers. However, the prognostic power of these systemic inflammatory markers is not identical. We aimed to establish a novel prognostic score based on systemic inflammatory markers. METHODS: Four hundred non-small cell lung cancer (NSCLC) patients who underwent surgery and were followed more than 5 years were included. Univariate and multivariate analyses were calculated by the Cox proportional hazards regression model. RESULTS: Among systemic inflammatory markers which were used for the previously reported indexes, preoperative serum C-reactive protein (CRP) and body mass index (BMI) were independent prognostic markers in multivariate analysis, while serum albumin level, neutrophil to lymphocyte ratio and platelet to lymphocyte ratio were not. Based on this result, a novel score was established. Patients with both normal CRP (< 0.13 ng/dL) and high BMI (> 20.6 kg/m2) were allocated a score of 0. Patients in whom only one of these abnormalities was present were allocated a score of 1, whilst those with both high CRP and low BMI were given a score of 2. Patients with score 0 had 84.44% of 5-year cancer-specific survival, while patients with score 1 - 2 had a 61.88%. On multivariate analysis, this novel score was an independent prognostic factor. CONCLUSION: This novel score based on CRP and BMI might serve as an efficient prognostic indicator in resected NSCLC.

Resected thymic large cell neuroendocrine carcinoma: A case report and review of the literature.

INTRODUCTION: Large cell neuroendocrine carcinoma (LCNEC) of the thymus is an extremely rare neoplasm. PRESENTATION OF CASE: We report a rare case of LCNEC of the thymus in a 55-year-old woman. Her chest roentgenogram during a routine checkup revealed an abnormal shadow in the mediastinal left upper lung field. Chest computed tomography showed an anterior mediastinal mass measuring 4.8 × 4.0 cm. Positron emission tomography with 18F-fluorodeoxyglucose (FDG) showed high FDG accumulation at the lesion. To obtain a definitive diagnosis and achieve complete resection, a surgery was performed. The postoperative diagnosis was thymic LCNEC; it was classified as a Masaoka stage III tumor due to the invasion of tumor cells into the left lung. Postoperatively, the patient received adjuvant chemotherapy and survived without any signs of recurrence for 30 months after surgery. DISCUSSION/CONCLUSION: The detailed clinical features of thymic LCNEC remain unknown because of its rarity. In total, 20 cases of resection for LCNEC, including the present case, have been reported in the English language literature; we have presented a review of these cases and discussed the optimal therapy for this rare and virulent tumor of the thymus.

Impact of preoperative hemoglobin level on survival of non-small cell lung cancer patients.

BACKGROUND: Only a few studies have reported any prognostic impact of the preoperative hemoglobin level itself in resectable non-small cell lung cancer (NSCLC). The survival impact of preoperative hemoglobin level and the relationship between hemoglobin and serum CEA level were investigated. PATIENTS AND METHODS: Two hundred and forty consecutive NSCLC patients were reviewed retrospectively. RESULTS: The 5-year survival of patients with low and those with a normal hemoglobin level was 42.99% and 73.47%, respectively. Both univariate and multivariate analyses indicated the independent prognostic impact of the hemoglobin level. The result for stage I patients was identical. Patients with normal hemoglobin could be subdivided into 2 groups based on their serum CEA level; the 5-year survival of patients with normal and those with elevated CEA was 81.72% and 57.24%, respectively. CONCLUSION: The preoperative hemoglobin level was a prognostic factor for NSCLC patients. The combined use of hemoglobin and CEA levels might be useful to predict the prognosis of patients.

Induction of apoptosis by intrapleural perfusion hyperthermo-chemotherapy for malignant pleural mesothelioma.

PURPOSE: Despite extensive clinical research, no effective therapy for advanced malignant pleural mesothelioma has been established. In this study, we induced apoptosis in patients with this disease, using intrapleural perfusion hyperthermo-chemotherapy, a new procedure developed in our surgical department. We then measured the tumorcidal effect. MATERIAL AND METHODS: Our study included 6 consecutive patients with malignant pleural mesothelioma (stage III: 5; stage IV: 1). Because of the advanced stage of the disease, none of the patients underwent tumor resection or pleurectomy. All patients, however, received perfusion treatment. Tumor cells collected from pleural effusions pre-and at 0, 24, and 48 h postperfusion were examined using an immunocytochemical stain to determine apoptosis. The percentage of positively stained cells was expressed as the apoptotic index. RESULTS: Preperfusion, the apoptotic index was 3.8%+/-2.0%, indicating spontaneous apoptosis of untreated tumor cells. Postperfusion, the apoptotic index at 0, 24, and 48 h was 22.8%+/-5.15%, 63.8%+/-8.2%, and 47.8%+/-6.9%, respectively. The patients had a median survival time of 30 months. No patient morbidity was associated with the perfusion treatment. CONCLUSION: In patients with malignant pleural mesothelioma, intrapleural perfusion hyperthermo-chemotherapy induced potent apoptosis of tumor cells, increasing immediately postperfusion and peaking at 24 h.

Squamous cell carcinoma of the hilar lymph node with unknown primary tumor: a case report.

We herein report a rare case of squamous cell carcinoma (SCC) located in the hilar nodes with unknown primary tumor. A 56-year-old man underwent a thoracotomy under the clinical diagnosis of lung cancer with hilar nodes involvement. The tumor was found at the hilus and resected without pulmonary resection. The pathological diagnosis of this tumor was metastatic SCC in hilar lymph nodes. Examinations of the whole body failed to detect a primary site of the SCC. The patient is doing well with no clinical sign of recurrence 32 months after surgery.

Malignant peripheral nerve sheath tumor with Horner's syndrome: a case report.

We report on a 42-year-old woman with malignant peripheral nerve sheath tumor (MPNST) arising from the cervical sympathetic nerve. A collar incision and partial sternotomy were performed at the second intercostal space. The mass was spindle shaped and connected to the sympathetic trunk on the cranial and caudal sides, and it compressed the left carotid sheath on the median side. After the patient's uneventful recovery from surgery, adjuvant radiotherapy was administered to the area of resection. The patient remains well 5 years after surgery with no evidence of recurrence.

The advanced lung cancer inflammation index is an independent prognostic factor after surgical resection in patients with non-small-cell lung cancer.

OBJECTIVES: The usefulness of a recently developed advanced lung cancer inflammation index (ALI) has been reported in advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer. However, no previous studies have examined the prognostic significance of ALI in patients with operable NSCLC. Therefore, the aim of this study was to explore the relationship between ALI and the prognosis of resected NSCLC. METHODS: Three hundred and forty-three patients with NSCLC who underwent surgery at our institution between 2008 and 2012 were included. The ALI score was calculated as body mass index × serum albumin/neutrophil to lymphocyte ratio. A Web-based software programme [Cutoff Finder (http://molpath.charite.de/cutoff/)] was used to determine the optimal cut-off value for ALI. The Kaplan-Meier methods and a multivariable Cox proportional hazards model were used to evaluate the potential prognostic factors. RESULTS: The optimal cut-off value of ALI was defined as 37.66. The low-ALI group (ALI < 37.66) displayed more adverse clinical characteristics. Furthermore, compared with patients in the high-ALI group (ALI > 37.66), those in the low-ALI group had significantly poorer survival rates. On multivariable analysis, gender, histological diagnosis, pN status, serum carcinoembryonic antigen level, serum C-reactive protein level and ALI were associated independently with cancer-specific survival. CONCLUSIONS: This study is the first to investigate whether ALI is useful for predicting postoperative survival in patients with NSCLC. Preoperative ALI might serve as a potentially clinically valuable marker of the prognosis for patients with operable NSCLC.

Comparison of Inflammation-Based Prognostic Scores in Patients undergoing Curative Resection for Non-small Cell Lung Cancer.

BACKGROUND: Inflammation-based prognostic scores, including Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII) and advance lung cancer inflammation index (ALI) are reported to be associated with survival in patients with non-small cell lung cancer (NSCLC). However, at present, there are no studies that compared these scoring systems for resectable NSCLC. METHODS: Three hundred forty-one NSCLC patients who underwent surgery at our institution were included. The optimal cut-off values of SII and ALI were calculated by the Cutoff Finder. The area under the receiver operating characteristics curve (AUC) was calculated to compare the predictive ability of each of the scoring systems. Univariate and multivariate analyses were performed to identify the clinicopathological variables associated with overall survival. RESULTS: The optimal cut-off value of SII and ALI were 471.2 × 109/L and 37.66, respectively. All scores were significantly related to the 5-year cancer-specific survival. The ALI consistently had a higher AUC value in comparison with other inflammation-based prognostic scores. A multivariate analysis showed that GPS and ALI were independently associated with overall cancer-specific survival. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate that GPS and ALI appear to be superior to other inflammation-based prognostic scores in patients undergoing potentially curative resection for NSCLC.