Is lung resection appropriate for late octogenarians? Surgical outcomes of patients aged ≥ 80 years with lung cancer.

PURPOSE: This study aimed to determine the outcomes and prognostic factors associated with octogenarians who underwent pulmonary resection for lung cancer. METHODS/PATIENTS: From 2009 to 2018, 76 octogenarians underwent pulmonary surgery for lung cancer at the Kanazawa Medical University, Japan. They were divided into two groups (early and late octogenarians), and their clinicopathological characteristics and outcomes were investigated. Overall survival rates and recurrence-free survival rates were determined using Kaplan-Meier curves. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Limited surgery was performed more often in the late octogenarian group; however, most perioperative factors were not significantly different between the two groups. The 3-year overall survival and recurrence-free survival rates were 61.2% and 52.8%, respectively. The median observation period was 37.5 (8.9-112.3) months postoperatively. Kaplan-Meier curves showed that age ≥ 85 years (late octogenarian), smoking history, and squamous cell carcinoma on histology were associated with worse survival rates. Multivariate analysis identified age ≥ 85 years (late octogenarian) (p = 0.011) and cigarette smoking (p = 0.025) as unfavorable prognostic factors for overall survival and recurrence-free survival, respectively. CONCLUSIONS: Most octogenarians with an indication for surgery can tolerate pulmonary surgery. However, owing to the limitations of this retrospective, single-center study, future studies involving multiple-institutions are required to confirm our findings.

[Descending necrotizing mediastinitis].

We treated of 3 patients with descending necrotizing mediastinitis that is often to be fatal. There are 3 important issues regarding the treatment of this disease. First, the precise sites of abscess should be determined by computed tomography (CT) scans from the neck to diaphragm. Second, effective drainage of the neck and mediastinal abscess should be carried out immediately when the sites of abscess are determined. Third, drainage under video-assisted thoracic surgery (VATS) is an appropriate treatment because VATS is less invasive and provides an easier placement of the drainage tubes at abscess sites.

[Complete resection of an advanced mediastinal nonseminomatous germ cell tumor with multiple distant metastases after down-staging by chemotherapy].

A mediastinal nonseminomatous germ cell tumor was completely resected after down-staging by chemotherapy despite the presence of multiple distant metastases. A 22-year-old female was admitted for superior vena cava (SVC) syndrome. Her SVC was obstructed by a large anterior mediastinal tumor; she also exhibited distant metastases on a left rib, in the liver, and multiple in the lung. The blood alpha-fetoprotein (AFP) level was extremely elevated to 57,530 ng/ml. Four courses of BEP therapy [cisplatin (CDDP), bleomycin (BLM), etoposide (VP-16)] and a high dose chemotherapy followed by a peripheral blood stem cell transplantation made the tumor become smaller and effected its down-staging. Residual mediastinal tumor with an intravascular tumor in SVC was completely resected. The SVC was reconstructed by an artificial vessel graft. A mediastinal nonseminomatous germ cell tumor, even though it has multiple distant metastases, can achieve down-staging and complete resection by a chemotherapy based on scientific evidence.

[Multidisciplinary treatment of lung cancer in 21st century].

Lung cancer is the leading cause of cancer deaths in Japan. Recently, big progress in the treatment of lung cancer has been achieved, such as new anti-cancer drugs, molecular targeted therapy, stereotactic radiotherapy, etc. Multidisciplinary approach has been required to the therapy for lung cancer patients. In this paper, we introduce The 21st Century Multidisciplinary Center in Kanazawa Medical University, and the Hokuriku Training Program for Making Specialists in Cancer Treatment.

[Comparison of the images in virtual bronchoscopy under different conditions].

OBJECTIVE: We report herein the comparison of the virtual bronchoscopy (VB) images which were constructed with 2 different computed tomography (CT) scanners combined with 3 different applications in 2 healthy adult volunteers. METHODS: CT scanners were multi-detector row CT (MDCT) [64 detectors] and MDCT (16 detectors). Applications, by which VB images were made, were Leonardo (Leo), Ziostation (Zio), and Plus XNVZ2 (Plus). The image quality was evaluated by 3 expert bronchoscopists. RESULTS: The change of the threshold value was necessary in Leo for practical use in subsegmental bronchi and more distal area, but unnecessary in Plus or Zio. When Plus was used, the VB images from the data obtained with MDCT (16 detectors) and MDCT (64 detectors) had almost equal quality. CONCLUSIONS: Although the process to construct VB images was different in each application, it was regarded that Plus was not inferior to Zio or Leo in VB image quality.

[Huge right atrial myxoma].

Myxomas are account for approximately half of primary cardiac tumors, and 75% cases originate in left atrium. We report our experience of a right atrial myxoma. A 68-year-old woman was referred to us due to anorexia, general fatigue and facial edema. Echocardiogram, computed tomography (CT), magnetic resonance imaging (MRI), and catheter angiocardiogram revealed a huge tumor in right atrium. The tumor was resected completely with the attached right atrial free wall under cardiopulmonary bypass. Pathological examination showed myxomatous tissue. Postoperative course was uneventful. She discharged the hospital on the 37th day after the operation, and is now doing well without any symptoms.

[Mediastinal lymph node metastasis of thyroid cancer occurring 15 years after the initial operation; report of a case].

A 71-year-old woman was found to have an abnormal shadow on a chest X-ray. Fifteen years earlier she had undergone a subtotal thyroidectomy for thyroid cancer without any lymph node metastasis. Chest computed tomography (CT) revealed a mediastinal tumor with full of blood stream. Since the positron emission tomography (PET) disclosed an increased uptake of fluoro-2-deoxy-D-glucose (FDG) in the tumor, a malignant lymphatic tumor was therefore suspected. An immunohistological examination of biopsy specimens taken by thoracoscopic procedure demonstrated tumor to be lymph node metastasis of the previous thyroid cancer. After a tumor resection by means of a thoracotomy and total thyroidectomy, the patient was scheduled to receive radioiodine therapy. The previously reported cases are also herein reviewed.

CPEB1 mediates epithelial-to-mesenchyme transition and breast cancer metastasis.

In mouse mammary epithelial cells, cytoplasmic polyadenylation element binding protein 1 (CPEB1) mediates the apical localization of ZO-1 mRNA, which encodes a critical tight junction component. In mice lacking CPEB1 and in cultured cells from which CPEB has been depleted, randomly distributed ZO-1 mRNA leads to the loss of cell polarity. We have investigated whether this diminution of polarity results in an epithelial-to-mesenchyme (EMT) transition and possible increased metastatic potential. Here, we show that CPEB1-depleted mammary epithelial cells alter their gene expression profile in a manner consistent with an EMT and also become motile, which are made particularly robust when cells are treated with transforming growth factor-ß, an enhancer of EMT. CPEB1-depleted mammary cells become metastatic to the lung following injection into mouse fat pads while ectopically expressed CPEB1 prevents metastasis. Surprisingly, CPEB1 depletion causes some EMT/metastasis-related mRNAs to have shorter poly(A) tails while other mRNAs to have longer poly(A) tails. Matrix metalloproteinase 9 (MMP9) mRNA, which encodes a metastasis-promoting factor, undergoes poly(A) lengthening and enhanced translation upon CPEB reduction. Moreover, in human breast cancer cells that become progressively more metastatic, CPEB1 is reduced while MMP9 becomes more abundant. These data suggest that at least in part, CPEB1 regulation of MMP9 mRNA expression mediates metastasis of breast cancer cells.

Relationship of lymph node metastasis to primary tumor size and microscopic appearance of roentgenographically occult lung cancer.

We investigated the relationship of lymph node metastasis to primary tumor size and microscopic appearance in 92 resected specimens obtained from patients with roentgenographically occult lung cancer (ROLC) located at a site along the airway between the main bronchus and the sub-subsegmental bronchi. Most of the patients were discovered by mass screening. All were treated surgically after bronchoscopic localization of cancer. The bronchial tree of the resected specimens was serial-sectioned into 2-mm thick blocks from the margin of resection to the sub-subsegmental bronchi. Bronchial wall invasion was noted in some blocks of all the specimens. The length of longitudinal extension (LLE) was defined as the product of the thickness and the number of consecutive blocks involved, counting from the most proximal to the most distal block. LLE was used as primary tumor size. Hilar and mediastinal lymph nodes were examined in 84 patients who underwent lymph node dissection. No nodal involvement was found in 59 cancers with LLE of less than 20 mm. Of 25 cancers with LLE of 20 mm or more, six showed nodal involvement. Eleven in situ carcinomas and four cancers of the "suspicious for invasion" type showed no lymph node metastasis. We contend that no lymph node dissection is required when pulmonary resection is performed for patients with ROLC if it is in situ carcinoma, if it is of the "suspicious for invasion" type, or if the LLE is smaller than 20 mm.

Relationship between length of longitudinal extension and maximal depth of transmural invasion in roentgenographically occult squamous cell carcinoma of the bronchus (nonpolypoid type).

This study was designed to verify our hypothesis that there are two different growth types in roentgenographically occult squamous cell carcinoma of the bronchus. Serial blocks prepared from the entire bronchial tree of 83 resected specimens of occult carcinoma were used for the evaluation of the relationship between the length of longitudinal extension and the maximal depth of transmural invasion. We prepared a length-depth diagram of 92 lesions, including multifocal carcinomas, which confirmed that there are at least two types: Most of these lesions are of the creeping type, which shows a marked superficial growth; the minority are of the penetrating type, which shows a marked downward growth. The diagram suggests that occult carcinoma has a propensity either for longitudinal growth along the bronchial lumen or for transmural growth into the bronchial wall at the time of occurrence. It is likely that the penetrating type grows rapidly and becomes advanced in a short time. Identification of longer lesions of the creeping type is occasionally problematical both at bronchoscopy and at surgical treatment. The stump is usually positive for carcinoma unless frozen sections or imprint specimens of the margin of resection are examined, because it is frequently difficult to identify the proximal end of extension by bronchoscopy.

Clinicopathological analysis of 19 cases of isolated carcinoma in situ of the bronchus.

Nineteen cases of isolated squamous cell carcinoma in situ (CIS) of the bronchus were described clinicopathologically from among 149 male heavy smokers with roentgenographically occult lung cancer discovered mainly by mass screening performed from 1982 to 1991. All 19 patients had positive sputum cytology tests and negative chest x-ray films and underwent lobectomy (except one who had segmentectomy because of poor lung function). Prior to operation, localization was accomplished by one to eight bronchoscopies using repetitive brush cytology and biopsy. Five cases were bronchoscopically invisible. Polypoid protuberance was noted in three cases, micronodular swelling in three, thickening of spur in five, and mucosal granularity in three. Histology by serial block sectioning showed that there was no nodal involvement in any cases; the maximum length or diameter was 12 mm. Thirteen tumors were < or = 4 mm, four of which were confined to the spur where they occurred. Follow-up data showed a favorable prognosis. Segmentectomy or sleeve resection of bronchus without mediastinal lymph node dissection may be adequate for CIS.

Relation between bronchoscopic findings and tumor size of roentgenographically occult bronchogenic squamous cell carcinoma.

A total of 105 lesions in 98 patients with roentgenographically occult bronchogenic squamous cell carcinoma were examined. The relationship of bronchoscopic findings to the depth of invasion into the bronchial wall and the length of longitudinal extension along the bronchus was documented. From viewpoints of the degree of difficulty of bronchoscopic detection and with reference to the height of the lesions, the bronchoscopic findings were classified into three categories: remarkable, minute, and hidden. Of the 105 lesions, 55 (52%) were remarkable, 27 (26%) were minute, and the remaining 23 (22%) were hidden. Of the 23 hidden lesions, 12 were within and 11 were beyond the range of endoscopic visibility. The maximal depth of bronchial invasion (mean +/- standard error) was 3.07 +/- 0.40 mm in the category designated remarkable and 1.62 +/- 0.47 mm in the category designated minute. The depth was 0.93 +/- 0.36 mm in the hidden lesions within the range of endoscopic visibility and 0.78 +/- 0.21 mm in the hidden lesions beyond the range of endoscopic visibility. The maximal length of longitudinal extension along the bronchus was 19.6 +/- 1.5 mm in the remarkable lesions, 9.9 +/- 1.4 mm in the minute lesions, 5.5 +/- 1.0 mm in the hidden lesions within the range of endoscopic visibility, and 8.6 +/- 2.1 mm in the hidden lesions beyond the range of endoscopic visibility. It is useful for predicting the depth of invasion to classify bronchoscopic findings into these three categories for the study of roentgenographically occult bronchogenic squamous cell carcinomas.

Results of surgical treatment for roentgenographically occult bronchogenic squamous cell carcinoma.

Ninety-four patients with roentgenographically occult bronchogenic squamous cell carcinoma had surgical resection. Fifty-three reported having no symptoms. In 83 carcinoma was detected by cytologic examination of the sputum during lung cancer screening. The carcinomas were located in segmental bronchi (34 cases), subsegmental bronchi (19 cases), divisional bronchi (17 cases), and subsubsegmental or more peripheral bronchi (15 cases). The number of cases classified by TNM staging were 16 Tis N0 M0, 72 T1 N0 M0, 4 T1 N1 M0, and 2 T2 N1 M0. Extrabronchial invasion of the resected carcinoma was observed in 17 lesions (16 cases). Five of six patients with lymph node metastasis in the resected specimens had carcinoma with extrabronchial invasion. Multiple primary lung cancers were observed in nine patients at the time of operation and in seven subsequently. Four of seven patients with subsequent primary lung cancer had surgical resection, and no recurrence was observed after the second operation. There were two deaths from lung cancer: One was caused by subsequent primary lung cancer and the other by mediastinal lymph node metastasis. In the 75 patients with intrabronchial cancer invasion and without lymph node metastasis who had complete resection, there was no local recurrence or metastasis of cancer. The 5-year survivals were 80.4% (death from all causes) and 93.5% (death from lung cancer). Although subsequent primary lung cancer is troublesome, operation is a reliable treatment for occult bronchogenic squamous cell carcinoma.

Prognostic assessment of 1310 patients with non-small-cell lung cancer who underwent complete resection from 1980 to 1993.

OBJECTIVE: The TNM staging system of lung cancer is widely used as a guide for estimating prognosis and selecting treatment modality. In 1997, the International Union Against Cancer and the American Joint Committee on Cancer have adopted a revised stage grouping for lung cancer. However, the validity of the new stage grouping has not been fully established. We investigated the prognoses of patients who had resection of non-small-cell lung cancer to confirm the validity of the revised classification. METHODS: A total of 1310 patients with non-small-cell lung cancer underwent complete resection and pathologic staging of the disease in our hospitals from 1980 through 1993. A pulmonary resection was performed with a systematic nodal dissection. The survivals were calculated with the Kaplan-Meier method on the basis of overall deaths, and the survival curves were compared by log rank test. RESULTS: There were significant differences in survival between patients with T1 N0 M0 and T2 N0 M0 disease and between those with T1 N1 M0 and T2 N1 M0 disease. However, there was no significant difference between patients with T2 NO M0 disease and those with T1 N1 M0 disease. No significant difference in survival was observed among patients with T2 N1 M0, T3 NO M0, and T3 N1 M0 cancer. Patients with different invaded organs of T3 subdivision (pleura, chest wall, pericardium, or diaphragm) had a different prognosis. There was no significant difference between patients with T3 N2 M0 disease and those with stage IIIB disease. CONCLUSIONS: We supported most of the revision, such as dividing stage I, dividing stage II, and putting T3 N0 M0 to stage IIB. Furthermore, we found some candidates for a subsequent revision, such as putting T3 N1 M0 to stage IIB, putting T2 N0 M0 and T1 N1 M0 together, regarding diaphragm invasion as T4, and putting T3 N2 M0 to stage IIIB.

Occult lung cancer beyond bronchoscopic visibility in sputum-cytology positive patients.

Sputum cytology is useful for screening and diagnosis of centrally located lung cancer in Japan. On the other hand, cancer beyond the range of bronchoscopic visibility in X-ray negative patients can be detected only with difficulty. Of 265 patients detected by sputum cytology in mass screening, 85 had an abnormal chest roentgenogram and the remaining 180 were roentgenographically occult. A total of 200 roentgenographically occult squamous cell carcinoma lesions were detected in the above 180 patients. A total of 45 of the 200 lesions were bronchoscopically occult. Twenty-two of the above 45 lesions were beyond the range of bronchoscopic visibility with a standard bronchoscope. The data obtained show that a sputum cytology positive, X-ray negative squamous cell carcinoma may lie outside the reach of a flexible bronchoscope. Thus, when it is difficult to localize a cancer, brushing of the peripheral bronchi beyond bronchoscopic visibility and chest computed tomography should be performed.

What kind of hilar lung cancer can be a candidate for segmentectomy with curative intent?: Retrospective clinicopathological study of completely resected roentgenographically occult bronchogenic squamous cell carcinoma.

Although a randomized control trial demonstrated that limited surgery for small peripheral lung cancers was not as curative as lobectomy, there have been no reports concerning segmentectomy for small hilar lung cancers. In this study, we analyzed the clinicopathological features of roentgenographically occult bronchogenic squamous cell carcinomas in order to select candidates for limited resection with curative intent. From April 1982 through June 1995, 105 roentgenographically occult bronchogenic squamous cell carcinomas whose proximal edge of the lesion was more peripheral than the orifice of the segmental bronchus were completely resected. The bronchoscopic findings of the lesions were classified into three categories: remarkable, minute and hidden. Moreover, in terms of the range of endoscopic visibility, the lesions were classified into two categories: lesions within the range of endoscopic visibility and those beyond it. If lymph nodes show no signs of metastasis, roentgenographically occult bronchogenic squamous cell carcinoma is regarded as localized carcinoma and can be a candidate for segmentectomy with curative intent. In cases with minute or hidden bronchoscopic findings or of lesions within the range of endoscopic visibility, metastatic lymph nodes were never observed. Accordingly, roentgenographically occult bronchogenic squamous cell carcinomas with minute or hidden bronchoscopic findings or those within the range of endoscopic visibility can be candidates for curative segmentectomy.

Preservation of alveolar epithelial fluid transport mechanisms in rewarmed human lung after severe hypothermia.

Although hypothermia abolishes alveolar fluid clearance in the in situ goat lung and in the ex vivo human lung, it is unknown whether alveolar fluid clearance resumes in lungs that are rewarmed after severe hypothermia. An isosmolar albumin solution was instilled into resected human lungs that were rewarmed to 37 degrees C after hypothermia (7 +/- 3 degrees C), and then alveolar fluid clearance was measured by the concentration of albumin in the alveolar fluid sample after 4 h. In control experiments in lungs that had not been cooled and rewarmed, alveolar fluid clearance was 11 +/- 2% over 4 h. In separate experiments, hypothermia completely abolished alveolar fluid clearance. However, alveolar fluid clearance resumed to a normal level of 12 +/- 1% over 4 h in the lungs that were rewarmed after hypothermia. Amiloride decreased alveolar fluid clearance by 47% in the rewarmed lungs. Terbutaline increased alveolar fluid clearance by nearly 300% in 2-h experiments in the rewarmed lungs (P < 0.05). The results of this study indicate that alveolar sodium-channel transport mechanisms are preserved in resected human lungs that are exposed to rewarming after hypothermia.

Multicentricity in resected occult bronchogenic squamous cell carcinoma.

The frequency and the treatment of multicentricity in 127 patients with resected roentgenographically occult bronchogenic squamous cell carcinoma were studied. The cumulative rate and the incidence of postoperative metachronous multiple primary lung cancer were 0.11 at 5 years after initial operation and 0.022 per patient-year, respectively. The cumulative rate and the incidence of second primary lung cancer, which includes synchronous and subsequent metachronous cancer in patients with initial lung cancer, were 0.17 at 5 years after the initial operation and 0.041 per patient-year, respectively. The cumulative rate and the incidence of third primary lung cancer in patients with second primary lung cancer were 0.47 at 5 years, which was significantly higher (p = 0.05) than that of second primary lung cancer, and 0.11 per patient-year, respectively. In all 12 patients with synchronous multiple primary lung cancer, no recurrence was observed after treatment, but 3 had subsequent multiple primary lung cancer. Among the 13 patients with postoperative metachronous multiple primary lung cancer, recurrence was observed in 1 of the 6 patients who underwent resection and in 2 of the 4 patients treated with laser or radiation therapy or both. The overall survival rate at 5 years after initial operation in patients with solitary and those with multicentric occult bronchogenic squamous cell carcinomas was 0.90 and 0.59, respectively.

Effect of long-term administration of ethyl eicosapentate (EPA-E) on local cerebral blood flow and glucose utilization in stroke-prone spontaneously hypertensive rats (SHRSP).

The objective of this study was to determine the effect of ethyl eicosopentate (EPA-E) on local cerebral blood flow (1-CBF) and local glucose utilization (1-CGU) in specific regions of the brain in stroke-prone spontaneously hypertensive rats (SHRSP). EPA-E (100 mg/kg body weight) or saline was orally administered to 8-week-old SHRSP. L-CBF and 1-CGU in the EPA-E-treated, saline-treated, and 8-week-old control rats were measured autoradiographically using 14C-iodoantipyrine and 14C-deoxyglucose (Sakurada's and Sokoloff's methods). The 1-CBF of the saline-treated group decreased significantly with age in all areas measured. EPA-E treatment alleviated the age-dependent decrease in 1-CBF in all areas, especially those in the basal ganglia. The 1-CGU of the saline-treated group did not change with age, however EPA-E treatment increased 1-CGU in all areas measured, though the changes were not significant. EPA-E ameliorated the decrease in cerebral blood flow and improved glucose metabolism in SHRSP suffering from severe hypertension. These results suggest that EPA-E may be useful in the prevention of stroke.

ONO-5046 is a potent inhibitor of neutrophil elastase in human pleural effusion after lobectomy.

The imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy and the effects of the neutrophil elastase inhibitors, sodium N-[2-[4-(2,2-Dimethylpropionyloxy)phenyl-sulfonylamino]benzo yl]aminoacetic acid (ONO-5046) and purified alpha1-antitrypsin, on neutrophil elastase activity were determined. The amount of neutrophil elastase complexed to alpha1-antitrypsin, measured by an enzyme-linked immunosorbent assay, was 170 times higher in pleural effusion than in blood 3 h after lobectomy. The alpha1-antitrypsin levels measured by laser nephelometry did not increase in either blood or pleural effusion. Although neutrophil elastase activity, measured by the hydrolysis of succinyl-(Ala)3-p-nitroanilide, was not detected in blood, it was increased in pleural effusion 3 h and 24 h after lobectomy. ONO-5046, but not alpha1-antitrypsin, reduced the neutrophil elastase activity in pleural effusion. There is an imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy. ONO-5046 is a potent inhibitor of neutrophil elastase activity in human pleural effusion.