Risk assessment of perioperative mortality after pulmonary resection in patients with primary lung cancer: the 30- or 90-day mortality.

OBJECTIVES: Although 30-day mortality rate is adapted to evaluate perioperative mortality after surgery, whether 90-day mortality rate adequately evaluates perioperative mortality remains unknown. Therefore, we analyzed 30- and 90-day mortality rates after pulmonary resection in patients with primary lung cancer. METHODS: A total of 2207 pulmonary resections for primary lung cancer performed between 1996 and 2010 at the Aichi Cancer Center Hospital were analyzed and divided into two groups of almost equal number: the early period group (1070 patients, 1996-2004) and the late period group (1137 patients, 2005-2010). Sixty-six and 34 patients died within a year during the early and late periods, respectively. The causes of death (recurrence, bleeding, sudden death, respiratory failure, and adverse event of chemotherapy), and 30- and 90-day mortality rates were investigated. RESULTS: The 30-/90-day mortality rates in the early and late period groups were 0.56/0.75 and 0.35/0.79 %, respectively. The postoperative survival days of 75 patients who died from recurrence within 1 year after pulmonary resection and 7 patients from bleeding or sudden death were more than 91 days and <30 days, respectively. The median postoperative survival of patients who died from respiratory failure was 67 days (range 20-142 days) in the early period and 100 days (range 47-149 days) in the late period. In the late period, it was difficult to assess perioperative mortality of pulmonary complications with 30-day mortality. CONCLUSIONS: A risk assessment of perioperative mortality after pulmonary resection should be performed using the 30- and 90-day mortality.

Significance of the serum carcinoembryonic antigen level during the follow-up of patients with completely resected non-small-cell lung cancer.

OBJECTIVES: The purpose of this study was to elucidate the detectability of recurrence and the prognostic significance of the serum carcinoembryonic antigen (CEA) levels in patients with completely resected non-small-cell lung cancer (NSCLC). METHODS: Five hundred and eighteen NSCLC patients who underwent complete resection at Aichi Cancer Center between April 2001 and March 2006 were enrolled in this study. The patient characteristics were as follows: the median age was 63 years; 331 tumours were classified as pathological stage I, 88 tumours were pathological stage II and 99 tumours were pathological stage III; 140 tumours were adenocarcinomas with epidermal growth factor receptor (EGFR) mutations, 268 tumours were adenocarcinomas with EGFR wild-type mutations and 110 tumours were other NSCLCs. The patients were divided into three groups: those with a normal CEA level before and 1-3 months after surgery (N group, n = 380), those with an elevated CEA level before surgery and a normal CEA level 1-3 months after surgery (HN group, n = 105) and those with an elevated CEA level 1-3 months after surgery regardless of the preoperative CEA level (H group, n = 33). The correlations between the changes in the serum CEA levels and the clinical outcomes were analysed. RESULTS: Recurrence developed in 122 patients (32%) in the N group, 49 patients (47%) in the HN group and 19 patients (58%) in the H group (P = 0.001). The sensitivity and specificity of an elevated serum CEA level during the follow-up period for detecting recurrence were 30 and 98% in the N group and 82 and 73% in the HN group, respectively. Twenty-seven asymptomatic recurrent tumours combined with an elevated serum CEA level were detected in the HN group. In the multivariate Cox regression analysis, the serum CEA level 1-3 months after surgery had prognostic value for overall survival. CONCLUSIONS: In completely resected NSCLC patients, measuring the serum CEA level during the follow-up period is useful in patients in whom an elevated level normalizes after surgery, and the serum CEA level 1-3 months after surgery is considered to have prognostic significance regarding survival.

Paravertebral block via the surgical field versus epidural block for patients undergoing thoracotomy: a randomized clinical trial.

PURPOSE: A paravertebral block (PVB) given via the surgical field can be safer and technically simpler than an epidural block (EP) for postoperative pain control. We conducted this clinical trial to confirm the effectiveness of PVB after thoracotomy. METHODS: In this non-inferiority trial, patients were randomly assigned to receive PVB (n = 35) or EP (n = 35). The primary endpoint was the pain assessed using the visual analog scale (VAS) at rest, 2, 24, and 48 h after thoracotomy, with the non-inferiority margin set at 15 mm. The secondary end points were the pain assessed using the VAS on exercising and on coughing, 2, 24, and 48 h after surgery, respectively, and the complications and need for additional analgesic agents. RESULTS: This trial revealed that PVB was not inferior to EP with respect to the primary end point: The mean VAS scores at rest, 2, 24, and 48 h after thoracotomy were 26.3, 10.8, and 8.3 mm in the PVB group and 23.6, 12.4, and 12.6 mm in the EP group, respectively (P < 0.01 for non-inferiority at all points). There were no significant differences between the groups in the incidence of complications or the need for additional analgesic agents. CONCLUSION: PVB may replace EP for postoperative pain control because of its technical simplicity and safety.

How long should small lung lesions of ground-glass opacity be followed?

INTRODUCTION: Pulmonary ground-glass nodules are frequently encountered. The purpose of this study was to evaluate the natural history of them and to gain some insights on how to follow them up. METHODS: We retrospectively studied patients with pulmonary nodules that met the following criteria: (1) tumor diameter of 3 cm or less, (2) ground-glass opacity proportion of 50% or more, and (3) observation without treatment for 6 months or more. Between 1999 and 2012, 108 pulmonary lesions in 61 patients fulfilled these criteria. We reevaluated their computed tomography images and analyzed changes in their size. RESULTS: The tumors were 1 cm or lesser in size in 69 lesions, 1.1 cm to 2 cm in 34, and 2.1 cm to 3 cm in five. The proportion of solid lesions was 0% for 82 lesions, 1% to 25% for 19, and 26% to 50 % for seven. At the median observation period of 4.2 years, 29 lesions had become larger, whereas the remaining 79 had persisted without changing in size (±1 mm). The median size change in the nodules that grew was 7 mm (range, 2-32 mm). All 29 tumors began to grow within 3 years of their first observation: 1 year or lesser in 13 lesions, after 1.1 years to 2 years in 12, and after 2.1 years to 3 years in four. CONCLUSIONS: Some small lung lesions exhibiting ground-glass opacity persisted without changes in size, whereas others grew gradually. The tendency to grow was clear within the first 3 years in all cases. Therefore, we conclude that these lesions should be followed for at least 3 years.

Solitary pulmonary metastasis from lung cancer harboring EML4-ALK after a 15-year disease-free interval.

It is often difficult to differentiate metachronous primary lung cancers from local pulmonary recurrences when the histopathological findings are similar. A 43-year-old man underwent right upper lobectomy with lymph node dissection for primary lung adenocarcinoma (p-T2aN0M0, stage IB). Fifteen years later, he developed a lung nodule in his right middle lobe. The tumor was preoperatively thought to be a metachronous second primary lung adenocarcinoma, and was surgically resected. Histopathological findings for both tumors were of poorly differentiated adenocarcinoma with mucus production. Both tumors also harbored the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene (variant 3a+b). Based on this molecular finding, the pulmonary nodule was considered to be a recurrence after very long latent period.

Pulmonary metastasectomy for gastric cancer: a 13-year single-institution experience.

PURPOSE: Pulmonary metastases from gastric cancer are rare, and the role of surgery is unclear. The purpose of this study was to determine which patients with metachronous metastatic gastric cancer (MGC) might benefit from pulmonary resection. METHODS: Between 1998 and 2011, 12 patients underwent 14 pulmonary resections for MGC. We reviewed their clinical courses and evaluated their radiological findings. RESULTS: Solitary pulmonary lesions were identified for 11 metastases, and the remaining three showed multiple pulmonary lesions. Six patients received treatment for the metastases before pulmonary resection. Lobectomy was performed for five lesions and wedge resection was performed for the remaining nine lesions. At the median follow-up time of 23.0 months, four patients were alive without disease, and the median DFS following pulmonary resection was 6.6 months. The overall 5-year survival rate following pulmonary resection was 58.4 %. In a univariate analysis, the number of lesions and the tumor doubling time (TDT) were significant predictors of the DFS, although prior treatment was not a significant predictor of the DFS. CONCLUSION: Pulmonary resection for MGC might be an effective therapeutic option when there is a solitary metastatic lesion that has a long TDT, even if the patient has been previously treated for metastases.

Genetic and Prognostic Differences of Non-small Cell Lung Cancer between Elderly Patients and Younger Counterparts.

Many elderly patients suffer from lung cancers, but it is not clear if their lung cancers differ from those of younger patients. In this study, we compared genetic and prognostic characteristics of lung cancers of patients aged ≥75 years with those of patients aged ≤ 64 years. In the genetic analysis, we explored 292 surgically treated non-squamous cell lung cancers with known mutational status of epidermal growth factor (EGFR) and anaplastic lymphoma kinase (ALK). In the prognostic analysis, we retrospectively analyzed 405 surgically treated non-small cell lung cancers (NSCLCs) before the era of routine clinical application of post-surgical adjuvant chemotherapy. Postsurgical recurrence-free survival (RFS) was compared between elderly patients and younger counterparts. The genetic analysis showed elderly non-squamous cell lung cancer patients to have higher prevalence of EGFR mutations (53.1 % vs 42.0%, P = 0.15) and lower prevalence of the ALK translocation (0 % vs 4.5%, P = 0.23) than their younger counterparts. The prognostic analysis showed postsurgical RFS was similar between the elderly NSCLC patients and the younger patients. However in multivariate analysis, adjusting for gender, smoking status, pathological stage, and histology, elderly patients had significantly worse prognoses (HR 1.57, 95% CI, 1.08-2.29; P = 0.02) compared with younger patients. These results suggest differences in genetic and prognostic aspects between elderly lung cancer patients and younger lung cancer patients.

Clinicoradiologic characteristics of patients with lung adenocarcinoma harboring EML4-ALK fusion oncogene.

INTRODUCTION: The fusion oncogene of echinoderm microtubule-associated protein like 4 (EML4) and anaplastic lymphoma kinase (ALK) defines a new molecular subset of non-small-cell lung cancer. We explored the EML4-ALK gene in a relatively large cohort and reviewed the clinicoradiologic background of the patients. METHODS: We studied 720 patients with lung adenocarcinoma. The clinicopathological characteristics of each patient were compared among the subgroups stratified by the EML4-ALK gene status. For radiographic evaluation, we scored the proportion of the ground-glass opacity (GGO) component and calculated the tumor disappearance rate (TDR) in each tumor in the cohort of 168 patients that were extracted by using a case-matching procedure. RESULTS: Twenty-eight (3.9%) patients harbored the EML4-ALK gene. Younger age (p=0.001), no or light history of smoking (p=0.05) and normal serum carcinoembryonic antigen (CEA) level (p=0.04) were characteristics of the patients with EML4-ALK. No significant difference was observed for overall and disease free survival between the two groups. All but one tumor in the EML4-ALK-positive group exhibited no GGO, whereas half of the tumors (69/140 patients) in the EML4-ALK-negative group exhibited some GGO (p=0.0004). The mean TDRs were 0.33 and 0.54, respectively, which was significantly lower in the positive group (p=0.0006). CONCLUSIONS: We identified younger age, no or light history of smoking, and normal serum CEA as clinical features of patients with EML4-ALK-positive lung adenocarcinoma. In addition, EML4-ALK-positive tumors exhibited a solid pattern on CT. These features may be of value in predicting for patient selection for ALK inhibition therapy in the absence of genetic screening.

Patterns of recurrence and outcome in patients with surgically resected small cell lung cancer.

BACKGROUND: Although prophylactic cranial irradiation (PCI) in limited-stage (LS) small cell lung cancer (SCLC) patients who are surgically resected and treated with adjuvant chemotherapy is considered to be a reasonable treatment option, the efficacy of PCI for those patients remains unclear. METHODS: The records of 28 patients with SCLC undergoing curative surgery at the Aichi Cancer Center Hospital between 1995 and March 2008 were retrospectively reviewed to assess patterns of relapse and overall survival. RESULTS: The patients were 27 men and 1 woman. Eight patients underwent induction chemotherapy. Fourteen patients (50%) had pathologic stage (p-stage) I disease, 7 patients (25%) had p-stage II, and 7 patients (25%) had p-stage III. Nineteen patients underwent adjuvant chemotherapy and one patient received adjuvant chemoradiotherapy. There were a total of 13 deaths and 8 were disease-related. Most patients developed hematogenous distant metastases before their death. The 5-year overall probability of survival was 47%. Ten (36%) of the 28 patients had a relapse. Two had a local relapse alone, one patient had combined local and distant relapses, and seven patients had distant metastases alone as their first site of failure. Four patients with p-stage II/III disease developed brain metastases with a cumulative incidence at 1 and 2 years of 25 and 36%, respectively. CONCLUSIONS: Our retrospective study suggested that PCI might have a role in surgically resected patients with p-stage II/III SCLC because of their relatively high frequency of brain metastasis.

Efficacy of erlotinib for brain and leptomeningeal metastases in patients with lung adenocarcinoma who showed initial good response to gefitinib.

INTRODUCTION: The efficacy of high-dose (1250 mg/d) gefitinib for the treatment of leptomeningeal metastasis in a patient with lung cancer harboring a mutation in the epidermal growth factor receptor (EGFR) gene was previously reported. We speculate that erlotinib, instead of high dose of gefitinib, may be also effective for the treatment of central nervous system (CNS) lesions, as trough serum concentration of erlotinib is nine times higher than that of gefitinib. PATIENTS AND METHODS: Patients with lung cancer in whom CNS lesions developed after an initial good response to gefitinib for extra CNS lesions were enrolled in the study. Tumor response, performance status, neurologic symptoms, and survival were retrospectively evaluated. RESULTS: All seven patients had EGFR mutations in their primary tumors except one patient. The median interval between gefitinib withdrawal and erlotinib administration was 5 days. Three patients showed partial response, three had stable disease, and one had progressive disease. Performance status and symptoms improved in five patients. The overall survival from the initiation of erlotinib treatment ranged from 15 to 530 days (median, 88 days). CONCLUSIONS: Erlotinib was a reasonable option for the treatment of CNS diseases that appeared after a good initial response of extra CNS disease to gefitinib.

Comparison of methods for placing and managing a silastic drain after pulmonary resection.

We have been using a silastic drain [Blake drain (BD)] after pulmonary resection by different placement methods and reviewed the daily amount of drainage in each patient. A 19-Fr BD was placed for each of 110 patients. First, a drain was inserted from the anterior chest wall and the tip reached the dorsal part of the diaphragm [anterior-to-posterior (AP)]. For the others [posterior-to-anterior (PA); n=37], we inserted a drain from the lower intercostal space, turned it around the apex and placed its tip in the lower front. Patients in the AP group included those placed under a water seal (AP-WS; n=43) or suction (AP-SC; n=30). The reference group consisted of 68 patients with a 32-Fr plastic drain during the same period [conventional drains (CD)]. The amount of drainage on the day of surgery in the PA group was significantly higher than that in the AP-WS group (P<0.0001) and similar to that in the CD group (P=0.54). The mean amount of drainage on postoperative day 1 and total amounts accumulating during drain placement showed no significant differences between the four groups. A BD placed using a PA approach with suction might be efficient for drainage.

Clinicopathological features of small-sized non-small cell lung cancer with mediastinal lymph node metastasis.

INTRODUCTION: In clinical practice, peripheral small-sized lung cancers with positive mediastinal lymph nodes are sometimes detected. To understand the characteristics of these aggressive tumors, we reviewed the clinicopathological features of small-sized non-small cell lung cancer patients with mediastinal lymph node metastasis resected in our institution. METHODS: We studied 360 patients with small-sized lung lesions with a maximum diameter of 2 cm or less. The clinicopathological characteristics of each patient were reviewed and compared among the subgroups, which were stratified according to pathological nodal status. RESULTS: 21 patients (5.8%) had a positive mediastinal lymph node. Among them, 17 patients had lung lesions larger than 1.5 cm. No mediastinal nodal involvement was found in patients with squamous cell carcinomas. In contrast, mediastinal nodal involvement was significantly common in patients with poorly differentiated carcinoma (P=0.004) and high serum carcinoembryonic antigen levels detected during preoperative evaluation (P=0.006). None of the 14 patients with upper lobe tumor had a positive subcarinal lymph node. Lower lobe tumors frequently developed extensive multiple-level involvement, which included the upper mediastinum. Radiographic evaluation of pN2 patients using computed tomography revealed a total absence of ground-glass opacity, or the presence of a small area of ground-glass opacity. CONCLUSIONS: Most small-sized non-small cell lung cancer cases with mediastinal lymph node metastasis were invasive adenocarcinoma with poor differentiation, which usually showed a solid shadow without ground-glass opacity on computed tomography.