Keisuke Asakura

Percutaneous cryoablation of lung tumors: Feasibility and safety

PURPOSE To evaluate the safety and feasibility of cryoablation for lung tumors as well as the incidence of, and risk factors for, complications. MATERIALS AND METHODS This study included 193 cryoablation sessions for 396 lung tumors in 117 consecutive patients. Univariate and multivariate analyses were performed to assess risk factors for common complications. Changes in laboratory values were analyzed the day after cryoablation. RESULTS Pneumothorax, pleural effusion, and hemoptysis occurred after 119 (61.7%), 136 (70.5%), and 71 (36.8%) sessions, respectively. Phrenic nerve palsy, frostbite, and empyema occurred after one session each (0.52%). Proximal tumor implantation was observed in one of 471 punctures (0.20%). Of 119 sessions with pneumothorax, 21 (17.6%) required chest tube insertion and two (1.7%) required pleurodesis. Delayed and recurrent pneumothorax occurred in 15 of 193 sessions each (7.8%). A greater number of cryoprobes was a significant (P = .001) predictor of pneumothorax. Male sex (P = .047) and no history of ipsilateral surgery (P = .012) were predictors for the need for chest tube insertion, and no history of ipsilateral surgery (P = .021) was a predictor for delayed/recurrent pneumothorax. Greater number of cryoprobes (P = .001) and no history of ipsilateral surgery (P = .004) were predictors for pleural effusion. Greater number of cryoprobes (P < .001) and younger age (P = .034) were predictors for hemoptysis. Mean changes in white blood cell count, platelet count, hemoglobin level, and C-reactive protein level were 2,418/μL ± 2,260 (P < .001), -2.0 × 10(4)/μL ± 3.2 (P < .001), -0.77 mg/dL ± 0.89 (P < .001), and 3.0 mg/dL ± 2.9 (P < .001), respectively. CONCLUSIONS Percutaneous cryoablation could be performed minimally invasively with acceptable rates of complications.

Curcumin induces autophagy in ACC-MESO-1 cells.

Malignant pleural mesothelioma is known to be widely resistant to therapy and new treatment strategies are needed. Curcumin, which has a long history as a dietary spice is known to suppress the growth of multiple cancer lines, but the effects on mesothelioma cells are not well defined. In the present study we examined the effects of curcumin on ACC‐MESO‐1, which is a human derived mesothelioma cell line. We found that curcumin dose‐dependently reduced cell viability but did not induce apoptosis. Curcumin administration increased LC3B‐II/LC3B‐I expression, and induced the formation of autophagosomes on electron microscopy. These changes were attenuated by RNA silencing of atg5. From these findings it was speculated that induction of autophagy was at least in part involved in the reduction of cell viability by curcumin. Copyright

Percutaneous Cryoablation of Pulmonary Metastases from Colorectal Cancer

Objective To evaluate the safety and efficacy of cryoablation for metastatic lung tumors from colorectal cancer. Methods The procedures were performed on 24 patients (36–82 years of age, with a median age of 62; 17 male patients, 7 female patients) for 55 metastatic tumors in the lung, during 30 sessions. The procedural safety, local progression free interval, and overall survival were assessed by follow-up computed tomographic scanning performed every 3–4 months. Results The major complications were pneumothorax, 19 sessions (63%), pleural effusion, 21 sessions (70%), transient and self-limiting hemoptysis, 13 sessions (43%) and tract seeding, 1 session (3%). The 1- and 3-year local progression free intervals were 90.8% and 59%, respectively. The 3-years local progression free intervals of tumors ≤15 mm in diameter was 79.8% and that of tumors >15 mm was 28.6% (p = 0.001; log-rank test). The 1- and 3-year overall survival rates were 91% and 59.6%, respectively. Conclusion The results indicated that percutaneous cryoablation is a feasible treatment option. The local progression free interval was satisfactory at least for tumors that were ≤15 mm in diameter.

Factors affecting local progression after percutaneous cryoablation of lung tumors

PURPOSE To evaluate factors predicting local tumor progression after percutaneous cryoablation of lung tumors (PCLT). MATERIALS AND METHODS Seventy-one consecutive patients with 210 tumors (11 primary and 199 metastatic pulmonary neoplasms; mean maximum diameter, 12.8 mm) were treated with 102 sessions of PCLT. Rates of local tumor progression and technique effectiveness were estimated by Kaplan-Meier method. Multiple variables were evaluated with the log-rank test, followed by uni- and multivariate multilevel analyses to identify independent risk factors, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. All statistical tests were two-sided. RESULTS Median follow-up period was 454 days (range, 79-2,467 d). Local tumor progression occurred in 50 tumors (23.8%). One-, 2-, and 3-year local progression-free rates were 80.4%, 69.0%, and 67.7%, respectively, and technique effectiveness rates were 91.4%, 83.0%, and 83.0%, respectively. Existence of a thick vessel (diameter≥3 mm) no more than 3 mm from the edge of the tumor was assessed as an independent factor (HR, 3.84; 95% CI, 1.59-9.30; P = .003) associated with local progression by multivariate analysis. CONCLUSIONS Presence of a vessel at least 3 mm in diameter close to the tumor represents an independent risk factor for local progression after PCLT.

Effect of cutting technique at the intersegmental plane during segmentectomy on expansion of the preserved segment: Comparison between staplers and scissors in ex vivo pig lung

OBJECTIVE Cutting the intersegmental plane by using a stapler during segmentectomy might interfere with the expansion of the preserved lung due to visceral pleura caught in a staple line, especially in a large regional segmentectomy, such as left upper division or basal segmentectomy. We compared the preserved lung volume after segmentectomy among the methods using stapler, sharp dissection, and their combination for cutting the intersegmental plane in ex vivo pig lungs. We also examined a covering effect of polyglycolic acid mesh and fibrin glue. METHODS To assume a large regional segmentectomy in clinical practice, segments of the left caudal lobe except the lateral segment 2 (L2 segment) were resected, and the lung volume of the preserved L2 segment was measured. The intersegmental plane was cut by the following three methods: (1) stapler (n = 8); (2) scissors (n = 8); and (3) the combined method, that is, cutting the shallow lung tissue with scissors and the deep one with stapler (n = 8). The opened intersegmental plane was covered with polyglycolic acid mesh and fibrin glue. The air leakage was checked by injecting air through the bronchus at pressures of up to 30 cmH(2)O. Thereafter, normal saline was injected through the bronchus at pressures of 10, 20, and 30 cmH(2)O, to measure lung volumes by the volume-displacement method. RESULTS Polyglycolic acid mesh and fibrin glue prevented air leakage completely at up to 30 cmH(2)O. At the saline injection pressures of 10, 20, and 30 cmH(2)O, the mean volumes of L2 segment were 72 ± 14, 96 ± 14, and 109 ± 26 ml with the stapler; 86 ± 11, 117 ± 19, and 135 ± 39 ml with scissors; and 98 ± 10, 140 ± 20, and 155 ± 40 ml with the combined methods, respectively. The volume of the preserved L2 segment was significantly lower with the stapler method than with either the scissors or combined method at each pressure (p < 0.01). The difference was not significant between the scissors and combined methods. CONCLUSIONS Coverage with polyglycolic acid mesh and fibrin glue prevented air leakage from the opened intersegmental plane. The stapler interferes with the expansion of preserved lung in comparison to scissors or combined methods in a large regional segmentectomy.

Sentinel nodes in lung cancer: Review of our 10-year experience

Sentinel node (SN) identification in patients with lung cancer is useful not only to minimize lymph node dissection, but also to target the best lymph nodes for intraoperative frozen section during segmentectomy. Since 2000, we have identified the SN in lung cancer patients using radioisotope (RI). This review presents our data on SN identification, describing the following: the procedure, using a radioisotope tracer; the flow of Tc-99 tin colloid after the injection; the characteristics of patients whose SNs could not be identified; ex vivo SN identification; reliability of in vivo SN identification; the algorithm for reducing mediastinal lymph node dissection; the differences in SN identification between large and small radioisotope particles; SNs at segmental lymph nodes; SN navigation segmentectomy for clinical stage IA non-small cell lung cancer; and small metastasis in the SN.

Incidence of pleural recurrence after computed tomography-guided needle biopsy in stage I lung cancer.

Objective A risk of tumor seeding after percutaneous needle biopsy has been reported in various organs, including the lung. This study retrospectively evaluated the proportion of ipsilateral pleural recurrence after computed tomography-guided needle biopsy (CTNB) in p-stage I lung cancer patients. Methods Of the 321 patients diagnosed with p-stage I lung cancer, 124 underwent CTNB before surgery, while 197 underwent non-CTNB procedures, including bronchoscopic biopsy in 188 patients and thoracoscopic wedge resection in 9. These patients were retrospectively analyzed. Results While the tumor size was significantly larger in the non-CTNB group (25±9 mm) in comparison to the CTNB group (19±9 mm) (p<0.001), percentage of pleural, vascular, or lymphatic invasions were comparable between the two groups. Eight patients developed ipsilateral pleural recurrences, one (1%) in the CTNB group, and 7 (4%) in the non-CTNB group. Of these, 3 patients developed pleural recurrence only at first, 1 (1%) in the CTNB group, and 2 (1%) in the non-CTNB group. The differences in the proportions of these pleural recurrences between the 2 groups were not significant. Subgroup analyses by baseline characteristics such as tumor size, pT stage, or microscopic pleural invasion, showed that proportions of pleural recurrences in CTNB group were not high compared with non-CTNB group in each subgroup. Analysis of progression-free survival showed that recurrences in CTNB were not high compared with non-CTNB. Conclusions The pleural recurrence was not significantly increased after CTNB in p-stage I lung cancer patients in this particular study.

Prognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer

Objectives The aim of this study was to investigate the relationship between clinicopathological prognostic factors, including surgical margin distance and tumor spread through air spaces (STAS), and recurrence after limited resection for primary lung cancer. Methods We identified 508 cases of limited resection (12.8%) and examined their clinicopathological features. Using Cox regression analysis, we examined the significant prognostic factors for recurrence of limited resection. Finally, we conducted a histopathological evaluation of tumor STAS. Results Multivariate Cox analysis showed that the risk for local recurrence was significantly associated with STAS (hazard ratio = 12.24, p = 0.001) and a tumor margin less than 1.0 cm (hazard ratio = 6.36, p = 0.02). However, the presence of tumor STAS was not significantly associated with distant recurrence (p = 0.98). This lack of association of STAS with distant recurrence may be due to the small number of distant recurrences. In all, 76 cases (15.0%) (60 adenocarcinomas, nine squamous cell carcinomas, and seven others) were positive for STAS. The morphological STAS patterns were 12 single cells, 45 small cell clusters, and 19 large nests. There was no significant relationship between the recurrence rate and morphological STAS pattern. The STAS‐positive group was associated with the presence of micropapillary (p = 0.002) and/or solid components (p = 0.008) in patients with adenocarcinoma and with lymphovascular and pleural invasion (p < 0.001). Conclusions The presence of STAS and tumor margins less than 1.0 cm are significant risk factors for local recurrence in early‐stage lung cancer after limited resection. Thus, the presence of tumor STAS might be a pathological prognostic factor for patients with lung cancer who have undergone limited resection. However, the pathological and molecular significance of STAS remain to be clarified.

Clinicopathological, Immunohistochemical, and Genetic Features of Primary Lung Adenocarcinoma Occurring in the Setting of Usual Interstitial Pneumonia Pattern

Introduction: An association between usual interstitial pneumonia (UIP) and carcinogenesis has been well established. However, few detailed analyses have investigated the clinicopathological, immunohistochemical, and genetic features of patients with primary lung adenocarcinoma (ADC) with UIP (UIP‐ADC). Methods: We identified 44 patients with ADC in the setting of UIP (the UIP‐ADC group) (1.9%) from 2309 patients with primary ADC and compared clinicopathological, immunohistochemical, and genetic features between the UIP‐ADC group and patients with ADC without UIP (the non–UIP‐ADC group). Results: Clinicopathological features of UIP‐ADC included an older age at occurrence; male predominance; smoking history; predilection for the lower lobe; large tumor size; high incidence of lymph vessel invasion, pleural invasion, and lymph node metastasis; and poor survival rate. However, the cause of death of patients with UIP‐ADC was largely influenced by respiratory complications. Histologically, patients in the UIP‐ADC group could be stratified according to invasive mucinous‐predominant subtype. Genetically, patients in the UIP‐ADC group had lower EGFR and higher KRAS mutation rates compared with patients in the non–UIP‐ADC group. Conclusions: UIP‐ADC was associated with a poor prognosis owing to the high frequency of perioperative complications rather than the malignancy of the tumor itself. There was a high prevalence of the invasive mucinous‐predominant subtype in cases of UIP‐ADC. UIP‐ADC also had a low prevalence of EGFR mutations and a high prevalence of KRAS mutations. These findings suggest that UIP‐ADC should be distinct from non–UIP‐ADC.

Prognostic Impact of Preoperative Tumor Marker Levels and Lymphovascular Invasion in Pathological Stage I Adenocarcinoma and Squamous Cell Carcinoma of the Lung

Introduction: Some unfavorable prognostic factors for stage I non–small-cell lung cancers have been reported; however, they are not reflected in the current Tumor–Node–Metastasis classification. Methods: We retrospectively reviewed 629 patients who underwent complete resection of pathological stage I adenocarcinomas (ADs) or squamous cell carcinomas (SQs) at two institutes between 1996 and 2011. The correlation between clinicopathological characteristics and survival rates was analyzed to identify prognostic factors. Results: Multivariate analysis indicated that among ADs, high serum carcinoembryonic antigen levels (p = 0.04 for overall survival [OS]; p < 0.01 for recurrence-free survival [RFS]; p = 0.02 for disease-specific survival [DSS]), lymphatic permeation (p < 0.01 for RFS and DSS), and vascular invasion (p < 0.01 for OS and RFS; p = 0.03 for DSS) were independent prognostic factors. Among SQs, high squamous cell carcinoma antigen (SCC) (p < 0.05 for OS), and vascular invasion (p < 0.05 for RFS and DSS) were independently prognostic. We suggest that among completely resected tumors less than or equal to 5 cm without lymph node metastasis, the current stages IA and IB AD with high serum carcinoembryonic antigen levels, lymphatic permeation, or vascular invasion should be upgraded to stage IB and IIA, respectively. The current stage IA SQ with high SCC antigen levels or vascular invasion should be upgraded to stage IB. These reclassifications accurately reflect survival status (p < 0.04 in all comparisons). Conclusions: Some important differences in prognostic factors were observed between AD and SQ. High preoperative serum tumor marker levels and lymphovascular invasion should be included as additional criteria in the forthcoming Tumor–Node–Metastasis staging.