Ryu Kanzaki

Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT: Risk factors, pattern, and histopathological study

BACKGROUND Integrated F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is widely used for mediastinal lymph node (MLN) staging in patients with non-small cell lung cancer (NSCLC). However, FDG-PET/CT has certain limitations. Prediction of occult MLN metastasis could allow selection of candidates for preoperative cervical mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration. This study defined risk factors for occult MLN metastasis in patients with NSCLC patients who were diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT. METHODS Consecutive patients with NSCLC who underwent staging using integrated FDG-PET/CT as an adjunct to CT prior to lung resection from October 2006 to September 2009 were evaluated retrospectively. The prevalence of MLN metastasis in patients diagnosed as clinical N0-1 was analyzed according to clinicopathological factors such as tumor location, tumor size, histology, and FDG uptake by the primary tumor. Risk factors for occult MLN metastasis were defined by multivariate analysis. Patterns of occult MLN metastasis were also analyzed and the involved MLNs were further examined histopathologically. RESULTS The incidence of MLN metastasis was 11% (24 patients of 224). Multivariate analysis identified adenocarcinoma (P=0.04), tumors located in upper or middle lobe (P=0.02), tumor size >3 cm (P=0.01), and SUV(max) of primary tumor >4.0 g/ml (P=0.04) as significant risk factors for MLN metastasis. The pattern of occult MLN metastasis was typical for NSCLC cases. The size of metastatic foci were small, with 68% of foci smaller than 4.0mm. CONCLUSIONS The present study demonstrated that adenocarcinoma, tumors located in the upper or middle lobe, tumor size >3 cm, and SUV(max) of primary tumor >4.0 g/ml are risk factors for occult MLN metastasis in patients with NSCLC who were diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT. Patients with tumors located in the right upper or middle lobe are considered candidates for cervical mediastinoscopy because the involved metastatic mediastinal lymph nodes are easily accessible by these modalities.

Long-term results of surgical resection for pulmonary metastasis from renal cell carcinoma: a 25-year single-institution experience

OBJECTIVE Despite the report of new treatment options, surgery remains the best treatment for pulmonary metastases from renal cell carcinoma (RCC). Repeat resection is also an effective means for recurrent pulmonary metastases. The aim of the present study was to define the prognostic factors for survival after pulmonary metastasectomy from RCC based on a 25-year single-centre experience. METHODS Between 1973 and 2008, 59 thoracotomies on 48 patients (38 men, 10 women) were performed in our hospital. Repeat resections were performed in eight patients. The clinicopathological and surgical data of these patients obtained from the medical records were analysed. The time interval between lung resection and death, or latest follow-up, ranged from 3 to 177 months (median 39 months). Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Multivariate analysis was performed using the Cox multivariate proportional hazard model. RESULTS The cumulative 3-, 5- and 10-year survival rates were 60%, 47% and 18%, respectively. Multivariate analysis identified disease-free interval (DFI) (≥ 2 years) and complete resection as significant prognostic factors for survival. Among eight patients, who underwent repeat resection, two remain alive with no evidence of disease. These two patients had long DFI and long DFI-2 (time from first pulmonary metastasectomy to diagnosis of recurrent pulmonary metastasis). CONCLUSIONS The results showed that (1) surgical resection of pulmonary metastasis from RCC has a favourable outcome in selected patients, (2) DFI and completeness of resection are prognostic markers for survival after pulmonary metastasectomy and (3) repeat lung resection for metastatic RCC is a safe procedure that provides satisfactory patient outcomes.

Clinical value of F18-fluorodeoxyglucose positron emission tomography-computed tomography in patients with non-small cell lung cancer after potentially curative surgery: experience with 241 patients

OBJECTIVES F18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT), which allows differentiation between malignant and benign lesions based on difference in tissue glucose metabolism, has become increasingly important in lung cancer diagnosis. This study examined the clinical value of FDG-PET/CT in a large number of patients with non-small cell lung cancer (NSCLC) after potentially curative surgery. METHODS Four hundred and ninety FDG-PET/CT of 241 patients (143 males and 98 females; age range 38-87 years; mean 68.0 years) between May 2006 and February 2008 were retrospectively evaluated. All the 241 patients had undergone potentially curative surgery for NSCLC >6 months before FDG-PET/CT and their pathologic stages were stage I and II according to the tumor-node-metastasis (TNM) classification. A final diagnosis of recurrence was confirmed by histologic or cytologic examination of the disease or by clinical and radiologic follow-up image analysis. Confirmation of recurrence-free status was based on a clinical and radiologic image analysis follow-up period of at least 12 months with no evidence of active malignancy. The diagnostic performance of FDG-PET/CT was evaluated. Details of false results and incidental detection of diseases other than recurrent lung cancer by FDG-PET/CT was also analyzed. RESULTS Recurrences were confirmed in 35 (15%) patients, and 206 patients (85%) had no evidence of recurrence. FDG-PET/CT correctly diagnosed recurrence in 34 of 35 patients and provided true negative findings in 198 of 206 patients who had no evidence of recurrence (sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 97%, 96%, 96%, 81%, and 99%, respectively), indicating a high diagnostic performance. However, one patient had false negative studies and eight patients had false positive studies; misdiagnosis was more frequently in intrathoracic sites associated with postoperative changes. Malignancies other than recurrence were detected in nine of all 241 patients (4%) including five second primary lung cancers. CONCLUSIONS The present study demonstrated the high diagnostic performance of FDG-PET/CT in detecting recurrences in a large group of patients with NSCLC after potentially curative surgery. FDG-PET/CT is useful not only for diagnosis of recurrence but also for detection of other diseases.

Outcome of surgical resection for recurrent pulmonary metastasis from colorectal carcinoma.

BACKGROUND The outcomes after repeat pulmonary resection for colorectal cancer (CRC) and the factors associated with the prognosis of these patients remain uncharacterized. METHODS Data on 156 patients who underwent curative resection of pulmonary metastasis from CRC were reviewed. Repeat pulmonary resection was performed in 25 patients; the present study examined the outcomes and factors associated with prognosis after repeat pulmonary resection. RESULTS The 5-year survival rate after the first pulmonary resection was 56.2%. A multivariate analysis identified a histological type other than well-differentiated adenocarcinoma, a high prethoracotomy serum carcinoembryonic antigen (CEA) level, and the presence of hilar or mediastinal lymph node metastasis as poor prognostic factors for the first pulmonary resection. The 5-year survival rate after repeat pulmonary resection was 42.1%. Hilar or mediastinal lymph node metastasis at the time of the repeat resection was significantly associated with poor survival. CONCLUSIONS Repeat pulmonary resection for metastatic CRC provides satisfactory outcomes. Hilar or mediastinal lymph node involvement is consistently associated with a poor prognosis after the first and repeat pulmonary resections.

Outcome of surgical resection of pulmonary metastasis from urinary tract transitional cell carcinoma

There is little information on pulmonary metastasectomy of urinary tract transitional cell carcinoma (TCC). In this study, we examined the long-term outcome and the factors associated with long-term survival after pulmonary metastasectomy of urinary tract TCC based on a 20-year single center experience. Between 1984 and 2005, 18 patients (12 men, six women) underwent pulmonary metastasectomy of the urinary tract TCC in our hospital. The clinicopathological and surgical data of these patients obtained from the medical records were analyzed in this retrospective study. The time interval between lung resection and death, or latest follow-up ranged from two to 200 months (median 52). Survival analysis was conducted by the Kaplan-Meier method and log-rank test. The cumulative three- and five-year survival rates were 59.8% and 46.5%, respectively. The number of resected metastatic tumors (solitary vs. multiple) was associated with long-term survival (P<0.05). The five-year survival rate of patients with solitary metastasis was 85.7% while that of patients with multiple metastases was 20.0%. Pulmonary metastasectomy of urinary tract TCC is associated with a favorable outcome, and solitary metastasis is associated with long-term survival. Aggressive management of solitary pulmonary metastasis from a urinary tract TCC is feasible in selected patients.

Ectopic Hepatocellular Carcinoma Arising in the Left Triangular Ligament of the Liver

Hepatocellular carcinoma (HCC) rarely originates in extrahepatic liver tissue. Laparoscopic resection is widely used to treat HCC. This report presents a case of a patient with ectopic HCC arising in the left triangular ligament of the liver that was successfully treated by laparoscopic resection. A 59-year-old female presented with an elevated serum alpha-fetoprotein (AFP) level (2,508 ng/ml). Dynamic computed tomography demonstrated a tumor measuring 20 mm in diameter below the left diaphragm just adjacent to the spleen. The tumor showed contrast enhancement in the hepatic arterial phase and became less dense than the liver parenchyma in the portal phase. The patient was diagnosed with ectopic HCC arising in the left diaphragm and laparoscopic surgery was performed. The tumor was located in the left triangular ligament of the liver and had a stalk between the tumor and the liver. The tumor was resected, and the final diagnosis was moderately differentiated ectopic HCC arising in the left triangular ligament of the liver. The patient had an uneventful postoperative recovery and has experienced no recurrence over 18 months after the operation.

Clinical predictor of pre- or minimally invasive pulmonary adenocarcinoma: possibility of sub-classification of clinical T1a

OBJECTIVES A new pathological classification for pre- and minimally invasive adenocarcinoma has been established, with distinction prior to surgery crucial because of the extremely good prognosis. METHODS Of 412 patients who underwent surgery for lung cancer from 2008 to 2011, 110 classified as c-stage I had each of the following four parameters assessed for predictive power for pre- or minimally invasive adenocarcinoma and relapse-free survival (RFS): (i) whole tumour size (WS) shown by computed tomography (CT) , (ii) size of the solid (SS) component in CT findings, (iii) maximum standard uptake value in fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan images (SUVmax) and (iv) serum level of carcinoembryonic antigen. RESULTS For prediction of pre- or minimally invasive adenocarcinoma, the area under the receiver-operating curve was >0.7 for all the four parameters, while only SS was found to be an independent factor in multivariate logistic regression analysis. In Cox proportional hazard model analysis, SS and SUVmax were statistically significant, and SS was exclusively independent in multivariate analysis. Differences in RFS between T1a and T1b were more pronounced when using SS compared with WS. In the sub-classification of T1a, we used a breakpoint of 1.0 cm in SS (T1a-α and T1a-β), which resulted in a 2-year RFS rate of 1.00 for T1a-α (n=21), 0.89 for T1a-β (n=27) and 0.68 for T1b (n=26) (P=0.002 between T1a-β and T1b). CONCLUSIONS The SS parameter was useful to distinguish pre- and minimally invasive adenocarcinoma from other types of lung cancer, and set a T1a sub-classification.

Candida esophagitis complicated by an esophago-airway fistula: Report of a case

Candida esophagitis rarely involves life-threatening complications, such as necrosis, perforation, or fistula formation between the esophagus and the airway. We herein report a case of Candida esophagitis complicated by esophagobronchial and esophagopulmonary fistulas. The patient in our study was a 70-year-old man with a 3-month history of dysphagia. Based on endoscopy and histological findings, he was diagnosed with a coinfection of Candida spp. and herpes simplex virus. Antifungal and antiviral therapy was administered without success. The esophagopulmonary fistula formation and a lung abscess were identified 7 months later. The patient was deemed intolerable to an esophagectomy due to his poor general condition, thus necessitating a two-stage operation. A cervical esophagostomy and a tube drainage of the thoracic esophagus were followed by an esophageal bypass using the pedicled jejunum via an antethoracic route. Although the lung abscess resolved, the inflammation of the esophagus persisted. A fistula between the esophagus and the left main bronchus eventually formed postoperatively and the patient died due to respiratory failure.

The Role of Surgery in Metastatic Bladder Cancer: A Systematic Review

CONTEXT The role of surgery in metastatic bladder cancer (BCa) is unclear. OBJECTIVE In this collaborative review article, we reviewed the contemporary literature on the surgical management of metastatic BCa and factors associated with outcomes to support the development of clinical guidelines as well as informed clinical decision-making. EVIDENCE ACQUISITION A systematic search of English language literature using PubMed-Medline and Scopus from 1999 to 2016 was performed. EVIDENCE SYNTHESIS The beneficial role of consolidation surgery in metastatic BCa is still unproven. In patients with clinically evident lymph node metastasis, data suggest a survival advantage for patients undergoing postchemotherapy radical cystectomy with lymphadenectomy, especially in those with measurable response to chemotherapy (CHT). Intraoperatively identified enlarged pelvic lymph nodes should be removed. Anecdotal reports of resection of pulmonary metastasis as part of multimodal approach suggest possible improved survival in well-selected patients. Cytoreductive radical cystectomy as local treatment has also been explored in patients with metastatic disease, although its benefits remain to be assessed. CONCLUSIONS Consolidative extirpative surgery may be considered in patients with clinically evident pelvic or retroperitoneal lymph nodal metastases but only if they have had a response to CHT. Surgery for limited pulmonary metastases may also be considered in very selected cases. Best candidates are those with resectable disease who demonstrate measurable response to CHT with good performance status. In the absence of data from prospective randomized studies, each patient should be evaluated on an individual basis and decisions made together with the patient and multidisciplinary teams. PATIENT SUMMARY Surgical resection of metastases is technically feasible and can be safely performed. It may help improve cancer control and eventually survival in very selected patients with limited metastatic burden. In a patient who is motivated to receive chemotherapy and to undergo extirpative surgical intervention, surgery should be discussed with the patient among other consolidation therapies in the setting of multidisciplinary teams.

Podocalyxin influences malignant potential by controlling epithelial-mesenchymal transition in lung adenocarcinoma

Epithelial–mesenchymal transition (EMT) plays an important role in the progression of lung carcinoma. Podocalyxin (PODXL), which belongs to the CD34 family and regulates cell morphology, has been linked to EMT in lung cancer, and PODXL overexpression is associated with poor prognosis in several different classes of cancers. The aim of this study was to clarify the role of PODXL overexpression in EMT in lung cancer, and to determine the prognostic value of PODXL overexpression in tumors from lung cancer patients. The morphology, EMT marker expression, and migration and invasion abilities of engineered A549 PODXL‐knockdown (KD) or PODXL‐overexpression (OE) lung adenocarcinoma cells were examined. PODXL expression levels were assessed by immunohistochemistry in 114 human clinical lung adenocarcinoma specimens and correlated with clinical outcomes. PODXL‐KD cells were epithelial in shape, whereas PODXL‐OE cells displayed mesenchymal morphology. Epithelial markers were upregulated in PODXL‐KD cells and downregulated in PODXL‐OE cells, whereas mesenchymal markers were downregulated in the former and upregulated in the latter. A highly selective inhibitor of phosphatidylinositol 3‐kinase‐Akt signaling attenuated EMT of PODXL‐OE cells, while a transforming growth factor inhibitor did not, suggesting that PODXL induces EMT of lung adenocarcinoma cells via the phosphatidylinositol 3‐kinase pathway. In lung adenocarcinoma clinical specimens, PODXL expression was detected in minimally invasive and invasive adenocarcinoma, but not in non‐invasive adenocarcinoma. Disease free survival and cancer‐specific survival were significantly worse for patients whose tumors overexpressed PODXL. PODXL overexpression induces EMT in lung adenocarcinoma and contributes to tumor progression.