Impact of Sarcopenia on Surgical Outcomes in Non-small Cell Lung Cancer.

BACKGROUND: Sarcopenia influences overall survival (OS) and tumor progression in non-small cell lung cancer (NSCLC) patients. However, the impact of postoperative complications and the outcome of limited surgery have not been highlighted. Therefore, the aim of this study is to elucidate the prognostic impact of sarcopenia on surgical outcomes. PATIENTS AND METHODS: This study included NSCLC patients who had undergone lung cancer resection between 2007 and 2017. Sarcopenia was confirmed based on computed tomography of the cross-sectional area of the psoas muscle at the third lumbar vertebra level. We used propensity score-matched analysis to elucidate the impact of sarcopenia on postoperative complications and limited surgery. RESULTS: A total of 391 patients were enrolled, including 198 sarcopenic patients. Multivariate analysis showed that sarcopenia was an independent unfavorable prognostic factor associated with OS and recurrence-free survival [hazard ratio (HR), 3.33, P < 0.001; HR, 2.76, P < 0.001, respectively]. Regarding the incidence of postoperative complications, there was no difference between sarcopenic and nonsarcopenic patients (69/198 versus 55/193, P = 0.19). After propensity score matching, among patients without sarcopenia, the 5-year OS was lower in those with limited surgery than in those with standard surgery (70.7% vs. 96.4%, P = 0.011). In contrast, among sarcopenic patients, there was no difference in the 5-year OS between patients with limited surgery and those with standard surgery (53.2% vs. 60.7%, P = 0.66). CONCLUSIONS: Sarcopenia is a prognostic predictor for poor OS and may contribute to the selection of limited surgery for sarcopenic patients. Preoperative assessment of sarcopenia may provide clinically important information.

The Prognostic Impact of Pericardial Fat Volumes in Resected Non-small Cell Lung Cancer.

BACKGROUND: Pericardial fat (PF) has not been considered a prognostic biomarker for overall survival (OS) in lung cancer. This study was designed to elucidate the impact of PF on prognosis of resected non-small cell lung cancer patients. METHODS: We retrospectively reviewed a total of 349 patients who underwent lung resection and received high-resolution computed tomography in our institute. PF volume was calculated. PF extended vertically from the diaphragm to the bifurcation of the right main pulmonary artery. Propensity score matched analysis was used to compare OS between the high- and low-PF groups. RESULTS: PF volume increased according to body mass index (p < 0.001). Receiver operating characteristics (ROC) curve analysis for 3-year OS showed the possibility of better predictivity of PF than body-mass index (area under the curve, 0.66 vs. 0.61, p = 0.010). Cutoff level of PF volume was determined based on the ROC with 122 cm3. Five-year OS was poorer in the low-PF group (63.5% vs. 73.4%; p = 0.002). After propensity score matching, each group consisted of 89 cases. Five-year OS was poorer in the low-PF group (66.5% vs. 82.7%; p = 0.008). A Cox proportional hazards model showed low-PF volume was associated with poorer OS (hazard ratio, 2.14; p = 0.009). The number of respiratory-related deaths was higher in the low-PF group (10/89 vs. 2/89, p = 0.032). CONCLUSIONS: Low-PF volume may be associated with poor OS with an increase in the number of respiratory-related deaths. Patients with low-PF volume require careful follow-up after surgery.

Fabrication of tissue-engineered cell sheets by automated cell culture equipment.

Most cells for regenerative medicine are currently cultured manually. In order to promote the widespread use of regenerative medicine, it will be necessary to develop automated culture techniques so that cells can be produced in greater quantities at lower cost and with more stable quality. In the field of regenerative medicine technology, cell sheet therapy is an effective tissue engineering technique whereby cells can be grafted by attaching them to a target site. We have developed automated cell culture equipment to promote the use of this cell sheet regenerative treatment. This equipment features a fully closed culture vessel and circuit system that avoids contamination with bacteria and the like from the external environment, and it was designed to allow 10 cell sheets to be simultaneously cultured in parallel. We used this equipment to fabricate 50 sheets of human oral mucosal epithelial cells in five automated culture tests in this trial. By analyzing these sheets, we confirmed that 49 of the 50 sheets satisfied the quality standards of clinical research. To compare the characteristics of automatically fabricated cell sheets with those of manually fabricated cell sheets, we performed histological analyses using immunostaining and transmission electron microscopy. The results confirmed that cell sheets fabricated with the automated cell culture are differentiated in the same way as cultures fabricated manually.

Long-term impact of complications after lung resections in non-small cell lung cancer.

BACKGROUND: Postoperative complications after lung resection are common and fatal. The immediate effects of postoperative complications are related to poor prognosis; however, the long-term effects have not been assessed. Thus, this investigation aimed to clarify the long-term effects of postoperative complications among patients with resected non-small cell lung cancer (NSCLC). METHODS: This retrospective cohort study included 345 patients with resected NSCLC from a single institution. We used the Clavien-Dindo classification to classify postoperative complications. Postoperative complications were defined as complications with a Clavien-Dindo grade of ≥2. The Kaplan-Meier method was used to evaluate survival. Prognostic factors were analyzed using a Cox proportional hazard model. RESULTS: There were 110 patients with postoperative complications (31.9%). The 5-year overall survival (OS), recurrence-free survival (RFS), and cause-specific survival (CSS) rates were significantly lower in patients with complications than in those without complications [OS: 66.1%, 95% confidence interval (CI): 55.4-74.8% vs. 78.0%, 95% CI: 71.8-83.1%, P=0.001; RFS: 48.8%, 95% CI: 38.1-58.7% vs. 70.8%, 95% CI: 64.2-76.4%, P<0.001; CSS: 82.7%, 95% CI: 72.8-89.3% vs. 88.2%, 95% CI: 82.8-92.0%, P=0.005]. The 5-year OS was lower in the pulmonary complication group than in the other complication group (58.1%, 95% CI: 40.0-72.4% vs. 70.5%, 95% CI: 56.6-80.6%, P=0.033). Postoperative complications were indicated as a poor prognostic factor for OS (hazard ratio, 1.67; 95% CI: 1.11-2.53; P=0.002). CONCLUSIONS: Postoperative complications were associated with unfavorable OS because of the worse prognosis of postoperative pulmonary complications.

Postoperative C-reactive Protein Is a Predictive Biomarker for Survival After Non-small Cell Lung Cancer Resection.

BACKGROUND/AIM: Preoperative C-reactive protein (CRP) is well recognized as a prognostic factor of non-small cell lung cancer (NSCLC). The present study aimed to elucidate the prognostic impact of postoperative CRP in patients with NSCLC following lung resection. PATIENTS AND METHODS: We retrospectively reviewed 336 patients with NSCLC treated with lung resection. CRP levels were measured at postoperative week 6 (CRP6w; range: 4-8 weeks). Patients were divided into two groups based on CRP6w median value (5.0 mg/l); the 5-year overall survival (OS) as well as the recurrence-free survival (RFS) was evaluated in both groups. RESULTS: Five-year OS and RFS were worse in the high-CRP6w group than in the low-CRP6w group (62.9% vs. 82.9%; p<0.001, 48.4% vs. 76.1%; p<0.001, respectively). Subgroup analysis for pathological stage I and ≥II also revealed worse OS in the high-CRP6w group. Multivariate analysis revealed an association between high CRP6w and worse OS (hazard ratio, 2.23; p<0.001). CONCLUSION: CRP6w may serve as a prognostic biomarker in patients with resected NSCLC.

A 0.5-T pure-in-plane-field magnetizing holder for in-situ Lorentz microscopy.

A side-entry specimen holder capable of applying a 0.5-tesla in-plane magnetic-induction field for in-situ transmission electron microscopy was developed. Three miniaturized electromagnets with 300 × 300-µm pole area and 180-µm pole gap are stacked along the electron-beam path in the holder. The middle magnet is used for magnetizing the specimen, which is inserted into the pole gap by using a 40-µm-width cantilever for atomic-force microscopy. The upper and lower magnets are used to keep the electron beam parallel to the optical axis. Magnetic-field magnitude was determined on the basis of experimentally measured electron-deflection angles and induction-field profiles along the electron-beam path calculated by finite element electromagnetic simulation. Magnetization reversal in 300-nm-thick Nd-Fe-B magnets from the saturated state was in-situ observed by using the holder and a 1-MeV cold-field-emission transmission electron microscope. The observation revealed that domain-wall pinning occurred in different manners at the c-plane and non-c-plane grain boundaries. The holder was thereby shown to be useful for analysis of magnetization-reversal behaviors of hard magnetic materials.

[ST Segment Elevation on Electrocardiogram (ECG) during Pleural Lavage with Distilled Water;Report of a Case].

Pleural lavage with distilled water is often employed in lung resection to eliminate malignant cells. Here we report a case of transient ST segment elevation on electrocardiogram (ECG) during pleural lavage with distilled water. A 73-year-old female was referred to our hospital because of an abnormal shadow on a chest roentogenogram. Chest computed tomography scan revealed a mass in left S4+5 segment of left upper lobe. It was proved to be adenocarcinoma of the lung by transbronchial lung biopsy and she underwent left upper lobectomy. During pleural lavage with distilled water, ST segment was elevated on ECG. In this case, it was because that the pericardium was excised and the myocardium was exposed to distilled water during pleural lavage.

Impact of the favorable prognosis of patients with lung cancer adjoining bullae.

BACKGROUND: Lung cancer adjoining bullae (LC-AB) is an uncommon manifestation. The clinical characteristics and prognosis of LC-AB remain unclear. The aim of this study is to investigate the clinical features and overall survival (OS) of patients with LC-AB following lung resection compared to non-LC-AB group. METHODS: We retrospectively investigated 291 consecutive patients with lung cancer who underwent curative resection in a single institution between April 2007 and March 2015. A total of LC-AB was 52 patients. LC-AB was determined using thin slice computed tomography (CT) imaging and pathological findings. Survival analysis was calculated using the Kaplan-Meier method. We used a Cox proportional hazards model for the univariate and multivariate analysis to identify prognostic factors. RESULTS: The LC-AB group showed a higher frequency of younger patients (P=0.017), former or current smokers (P=0.011), men (P=0.021), tumor location in the upper lobe (P=0.031), moderately or poorly differentiated tumor histology (P<0.001), pleural indentation (P=0.007), and non-adenocarcinoma histology (P=0.016) than the non-LC-AB group. The 5-year survival and recurrence-free survival (RFS) rates were significantly higher in the LC-AB group than the non-LC-AB group (88.5% vs. 74.9%, P=0.010, 75.4% vs. 61.3%, P=0.030, respectively). Multivariate analysis using a Cox proportional hazard model of OS showed that LC-AB was an independent prognostic factor [hazard ratio (HR): 0.30, 95% confidence interval (CI): 0.12-0.77, P=0.012]. CONCLUSIONS: Patients with LC-AB had better OS than those with non-LC-AB. Thus, LC-AB may be an independent favorable prognostic factor following curative resection.

Impact of Postoperative Pneumonia Developing After Discharge on Long-Term Follow-up for Resected Lung Cancer.

BACKGROUND: Postoperative nosocomial pneumonia is a common immediate complication following lung resection. However, the incidence and mortality of pneumonia developing after discharge (PDAD) for lung-resected patients during long-term observation remain unclear. The aim of this study was to investigate the clinical features of PDAD in patients with resected lung cancer. METHODS: We conducted a retrospective cohort study of 357 consecutive patients with lung cancer who had undergone lung resection at a single institution, between April 2007 and December 2016. The clinical characteristics, pathological features, and overall survival were analyzed. Propensity score matched analysis was used for the evaluation of overall survival between PDAD and non-PDAD groups with adjusted relevant confounding factors. RESULTS: PDAD was observed in 66 patients (18.5%). The cumulative incidence of PDAD was 14.9% at 3 years and 21.6% at 5 years. Mortality of PDAD was 30.3%. Multivariate analysis demonstrated that the risk factors for PDAD were age (OR 1.07; P = 0.005), oral steroid use (OR 5.62; P = 0.046), and lower-lobe resection (OR 1.87; P = 0.034). After propensity score matching, 52 patients with PDAD and 52 patients without it were compared. The incidence of PDAD resulted in a worse 5-year overall survival (56.1 vs. 69.3%; P = 0.024). The Cox proportional hazards model indicated that PDAD was associated with poor overall survival (HR 1.99, P = 0.027). CONCLUSIONS: Our findings revealed a high incidence and mortality of PDAD among patients who had undergone lung resection with long-term follow-up. Therefore, PDAD could be associated with poorer overall survival.

Prognostic Impact of Postoperative C-reactive Protein for Non-small Cell Lung Cancer Following Lobectomy.

BACKGROUND/AIM: C-reactive protein (CRP) is associated with cancer progression; however, the prognostic impact of postoperative CRP remains controversial. The aim of this study was to investigate the prognostic significance of postoperative CRP in patients with resected non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 198 consecutive patients with NSCLC that had undergone lobectomy were retrospectively reviewed. CRP was measured on postoperative days 1, 3, and 5. Patients were divided into two groups according to the median of CRP on postoperative day 3 (CRP3); the high and low CRP3 groups (n=99, respectively). RESULTS: Five-year overall survival was significantly higher in the high CRP3 group than the low CRP3 (75.3% vs. 86.5%; p=0.016), as was the 5-year recurrence-free survival (62.7% vs. 73.0%; p=0.016). Multivariate analysis revealed that high CRP3 was associated with a favorable prognosis (hazard ratio(HR)=0.36; p<0.001). CONCLUSION: High CRP3 may be a favorable prognostic predictor in patients with NSCLC following lobectomy.

Real-time explosive particle detection using a cyclone particle concentrator.

RATIONALE: There is a need for more rapid methods for the detection of explosive particles. We have developed a novel real-time analysis technique for explosive particles that uses a cyclone particle concentrator. This technique can analyze sample surfaces for the presence of particles from explosives such as TNT and RDX within 3 s, which is much faster than is possible by conventional methods. METHODS: Particles are detached from the sample surface with air jet pulses, and then introduced into a cyclone particle concentrator with a high pumping speed of about 80 L/min. A vaporizer placed at the bottom of the cyclone particle concentrator immediately converts the particles into a vapor. The vapor is then ionized in the atmospheric pressure chemical ionization (APCI) source of a linear ion trap mass spectrometer. RESULTS: An online connection between the vaporizer and a mass spectrometer enables high-speed detection within a few seconds, compared with the conventional off-line heating method that takes more than 10 s to raise the temperature of a sample filter unit. Since the configuration enriched the number density of explosive particles by about 80 times compared with that without the concentrator, a sub-ng amount of TNT particles on a surface was detectable. CONCLUSIONS: The detection limit of our technique is comparable with that of an explosives trace detector using ion mobility spectrometry. The technique will be beneficial for trace detection in security applications, because it detects explosive particles on the surface more speedily than conventional methods.

Complications of bronchial stapling in thoracic surgery.

OBJECTIVE: The use of staplers for thoracic surgery has been widely accepted and regarded as a safe procedure. However, complications of stapling are occasionally experienced. The aim of this retrospective study was to analyze complications of bronchial stapling. METHODS: A retrospective multi-institutional review was conducted by the Central Japan Lung Cancer Surgery Study Group, comprising 29 institutions. All instances of bronchial stapling in thoracic surgery were reviewed during the research period. RESULTS: Bronchial stapling was performed 2,030 times, using 36 kinds of staplers. The total number of complications related to stapling was 36 (1.8 %); 31 events occurred intraoperatively and five events occurred postoperatively. The intraoperative complications were air leakage (N = 20) and stapling failure (N = 11), which were caused by stapler-tissue thickness mismatch (N = 17), stapler defect (N = 3), tissue fragility (N = 2), and unknown reasons (N = 9). In all 31 cases, intraoperative complications were recovered intraoperatively with additional suturing, and no further complications were observed postoperatively. The postoperative complications were bronchopleural fistula (BPF) (N = 4) and bleeding from the chest wall (intercostal artery) (N = 1). The rate of BPF was 0.2 % (4 of 2,030). Two of four BPFs induced critical conditions. Postoperative bleeding was caused by the use of Duet TRS(TM). Both total complications and BPF occurred more frequently in the main bronchus than in the lobar or segmental bronchus. No relationship was seen between the incidence of complications and cartridge colors in lobar bronchial stapling. The compression types of staplers were associated with the incidence of complication. CONCLUSIONS: Intraoperative and postoperative complications of bronchial stapling were studied. Generally, bronchial stapling in recent thoracic surgery was safe, but rare postoperative complications may induce critical conditions. Knowledge of potential complications and causes of bronchial stapling may decrease the incidence of stapling complications.

Differences in sensitivity to tumor-specific CTLs between primary and metastatic esophageal cancer cell lines derived from the same patient.

PURPOSE: MHC antigens and adhesion molecules, such as the intracellular adhesion molecule (ICAM-I), play an important role in cellular immune response. We examined the expression patterns of these molecules in both primary and metastatic esophageal carcinoma cells from the same patient and evaluated the cellular immune responses against these cells. MATERIALS AND METHODS: In the esophageal cancer patient (H122), tumor cell lines were established from primary and subcutaneous metastatic lesions. We compared the expression of cell surface molecules on the metastatic tumor cell line (H122SC) with that on the primary tumor cell line (H122ESO) using flow cytometry. Moreover, we analyzed the differences in cellular immune responses against these cell lines, which expressed similar levels of the Tara antigen, using the Tara antigen-specific CTL clone. RESULTS: H122SC ICAM-1 expression was significantly lower in H122ESO, and the Tara antigen-specific CTL clone produced lower levels of TNF in response to H122SC than H122ESO. ICAM-1 transfection into the H122SC rendered these cells as sensitive to the CTL clone as the H122ESO. CONCLUSION: The metastatic tumor cells displayed lower regulated ICAM-1 expression levels and were less sensitive to specific CTLs. ICAM-1 downregulation may be one mechanism by which tumor cells escape immunologic surveillance.

Preoperative CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer.

PURPOSE: This study investigated the preoperative serum levels of CYFRA 21-1 and CEA as prognostic factors in patients with stage I non-small cell lung cancer. SUBJECTS: This study evaluated 341 patients who had undergone a complete resection for stage I NSCLC between 2002 and 2008. RESULTS: The patients included 193 males and 148 females. The mean age of the patients was 69.2 years (range: 19-88). The histological types included 264 adenocarcinomas, 56 squamous cell carcinomas, 11 large cell carcinomas, and 10 other types of carcinoma. A pneumonectomy was performed in 2 patients, a bilobectomy in 7, a lobectomy in 255, a segmentectomy in 46, and partial resection of the lung in 31 patients. The positive rates for CYFRA 21-1 in the adenocarcinoma and squamous cell carcinoma patients were 33.3% and 76.8%, respectively. The positive rates for CEA in adenocarcinoma and squamous cell carcinoma patients were 23.8% and 26.8%, respectively. The 5-year survival rate after surgery in the normal CYFRA 21-1 group and the high CYFRA 21-1 groups were 92.8% and 75.4%, respectively, in the patients with stage I NSCLC. There was a significant difference between the 2 groups (p<0.0001). The 5-year survival rate according to the serum level of CEA in the patients with stage I NSCLC were 88.3% for the normal group and 76.3% for the high group. In a multivariate analysis using the variables found to be significant prognostic factors in univariate analysis, a high CYFRA 21-1 level was found to be a significant independent prognostic factor (95% confidence interval 1.213-5.442, p=0.014). CONCLUSION: A high preoperative CYFRA 21-1 level was a significant independent prognostic factor in patients with stage I NSCLC. The patients with a high CYFRA 21-1 level should carefully followed-up to rule out occult metastasis. Further clinical studies will be necessary to evaluate the efficacy of adjuvant therapy for the patients selected according to this criterion.

Phase II trial of adjuvant chemotherapy with bi-weekly carboplatin plus paclitaxel in patients with completely resected non-small cell lung cancer.

BACKGROUND: Adjuvant chemotherapy improves the prognosis of patients with non-small cell lung cancer (NSCLC) after a complete resection despite unacceptable toxicity and low compliance. METHODS: A total of 67 patients were enrolled in a multi-institutional study. The patients received chemotherapy with carboplatin (CBDCA) area under the curve of 3 and paclitaxel (PTX) 90 mg/m(2) every 2 weeks for six cycles after surgery. RESULTS: Fifty patients (74.6%) completed all cycles of therapy. The presence of grade 3 and 4 toxicities of neutropenia were 13.4, and 3.0%, respectively. Non-haematological adverse effects were infrequent and no treatment-related death was registered. The estimated disease-free survival and overall survival at 2 years were 89.0% and 88.8%, respectively. CONCLUSION: A bi-weekly schedule of CBDCA and PTX as adjuvant chemotherapy showed an acceptable toxicity and favourable feasibility in Japanese NSCLC patients after complete tumor resection. Consequently, it is desirable to validate this regimen in a future randomized clinical trial.

Time trends of surgical outcome in patients with non-small cell lung cancer.

PURPOSE: A surgical resection is a potentially curative treatment for non-small cell lung cancer (NSCLC). This study investigated the time trends of the surgical outcome in patients with NSCLC. METHODS: This study clinicopathologically evaluated 1487 patients who had undergone a resection for NSCLC between 1979 and 2008 during the five periods of 1979-1988, 1989-1993, 1994-1998, 1999-2003, and 2004-2008. RESULTS: The number of patients who underwent a resection during the five respective periods increased: 167, 261, 248, 382, and 429. The percentage of pathologic stage IA lung cancers was 16.2, 21.5, 23.0, 38.5, and 52.0% in each period, respectively, and it has risen rapidly in recent years. The percentage of adenocarcinoma has also progressively increased during each period: 49.1, 52.1, 54.7, 62.8, and 69.7%, respectively. The diameter of the tumors resected during each period was 36, 37, 38, 33, and 26 mm, respectively, showing that the tumor tended to be diagnosed at an increasingly smaller size. The postoperative 5-year survival rates during the five periods improved markedly: 34.1, 44.0, 44.9, 65.4, and 76.5%, respectively. Patients with pathologic stage IA lung cancer also exhibited increasingly higher 5-year survival rates during the five periods: 70.0, 71.2, 80.4, 89.2, and 88.7%, respectively. CONCLUSION: The prognosis of NSCLC patients has remarkably improved in recent years. The increase in the number of patients with adenocarcinoma in the early stage is thought to have strongly contributed to the favorable results. Thus, early diagnosis remains a key factor for improving the survival of lung cancer patients after surgical treatment.

Sleeve lobectomy for patients with non-small cell lung cancer.

PURPOSE: A sleeve lobectomy for lung cancer is a procedure intended both for the maintenance of lung function and for radical treatment. We investigated the clinico-pathological features and treatment responses of lung cancer patients who underwent sleeve lobectomy in our department. SUBJECTS: Among the 984 patients with non-small cell lung cancer who underwent resection in our department between 1994 and 2007, the subjects were 24 patients in whom a sleeve lobectomy was performed. RESULTS: There were 18 male and 6 female patients, with a mean age of 65 years. The histological type was diagnosed as squamous cell carcinoma in 14 patients, and adenocarcinoma in 10. Patients with either mucoepidermoid carcinoma (n=1) or carcinoid tumor (n=1) were excluded. The pathological stage was evaluated as IA, IB, II, IIIA, IIIB, and IV in 4, 1, 8, 8, 2, and 1 patient, respectively. Regarding post-operative complications, 4 patients required sputum aspiration with a bronchoscope from the 2nd to 7th post-operative day due to sputum retention. The 5-year survival rate in patients who underwent sleeve lobectomy was 70.0%. According to the pathological nodal status, the 5-year survival rates of N0, N1, and N2 were 100.0%, 87.5%, and 41.7%, respectively. The 5-year survival rates in squamous cell carcinoma and adenocarcinoma were 83.0% and 45.7%, respectively. CONCLUSION: Sleeve lobectomy facilitated the maintenance of residual lung function without serious perioperative complications. This finding suggests that patients with direct tumor invasion to the bronchus might be good candidates for a sleeve lobectomy, but not those with extra-nodal invasion.

Clinicopathological characteristics of invasive lobular carcinoma of the breast.

BACKGROUND: The clinical features of invasive lobular carcinoma (ILC) of the breast have remained unclear due to the rarity of such cases. This study investigated the clinical and pathological features of ILC. METHODS: The medical records of 413 patients with invasive breast cancer who underwent surgery in our department were reviewed. These cases included 13 patients with ILC (3.1%). RESULTS: The age of the patients ranged from 36 to 77 years old (mean, 56). The tumour size was evaluated as T1 in five patients, T2-4 in 8. The lymph node metastasis was diagnosed as negative in six patients, positive in six. In this patient population, 11 (85%) and nine (69%) patients were positive for oestrogen and progesterone receptors, respectively. The 5-year survival rate was 76.2%, which was not significantly different from other types of invasive breast cancer. Extensive intraperitoneal metastasis was observed in two of the three patients. Two patients had bilateral carcinoma and one patient had a multicentric lesion in the ipsilateral breast. CONCLUSION: Multicentric development of breast cancer and intraperitoneal metastasis were one of clinical characteristics of ILC. The prognosis of ILC was not significantly different from other types of invasive breast carcinoma.

Prospective phase II study of gefitinib in non-small cell lung cancer with epidermal growth factor receptor gene mutations.

BACKGROUND: This study prospectively assessed the efficacy of gefitinib and the survival benefit for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. METHOD: Patients with either recurrent disease after undergoing surgery or advanced NSCLC disease (IIIB or IV) which demonstrated EGFR mutations were eligible for this study. EGFR mutations in exons 19-21 were examined. The patients with EGFR mutations were enrolled in this study after obtaining their informed consent a second time, and they were thereafter treated with gefitinib. RESULTS: EGFR mutations were detected in 20 of 48 patients with NSCLC, and 19 patients were enrolled onto this study and treated with gefitinib. Seven patients had an exon 19 deletion, 10 had L858R, 1 had both, and 1 had an exon 19 deletion and G796A. The overall response rate was 63.2%, and the disease control rate was 89.5%. In patients with an exon 19 del and L858R, the response rates were 71.4% and 60.0%, respectively. The median progression-free survival time was 7.1 months, and the median survival time was 20.0 months. No life-threatening toxicity was observed. Four of five acquired resistant tumors showed an acquired T790M mutation. CONCLUSIONS: EGFR mutations in exons 19 or 21 are considered to be a good predictor of the efficacy of gefitinib.

Significance of Smoking as a Postoperative Prognostic Factor in Patients with Non-small Cell Lung Cancer.

INTRODUCTION: In this study, we investigated the influence of smoking on the postoperative prognosis in patients with non-small cell lung cancer. METHODS: The subjects consisted of 770 patients who underwent a resection of lung cancer in our department between 1994 and 2005. We compared the clinico-pathological findings between the smoking and never-smoking groups. The pack-year index (PYI) was used as a smoking index. RESULTS: The smoking group consisted of 569 patients (74%), and the never-smoking group consisted of 201 patients (26%). The smokers were composed of 492 men and 77 women. Among the adenocarcinoma patients, there were 293 (61%) smokers and 185 (39%) never-smokers. The patients with squamous cell carcinoma included 204 (95%) smokers and 10 (5%) never-smokers. The proportion of patients with stage IA disease was significantly higher in the never-smokers than that of the smokers. The 5-year survival rate after surgery was 66% in the never-smoking group; however, the rates were 56% in patients with a PYI more than or equal to 20, and 55% in those with PYI more than 20. Seventy-nine (13.9%) patients in the smoking group and seven (3.5%) patients in the never-smoking group died of other diseases, with a significant difference (p < 0.01). Of these patients, 44 (56%) and 13 (16%) in the smoking group died of respiratory and cardiovascular disorders, respectively. In our series, excluding those who died of other diseases, there were no significant differences in the postoperative prognosis. CONCLUSIONS: In the smoking group, the prognosis was poorer than that in the never-smoking group. The higher proportion of early stage disease (stage IA) and female gender were major causes of the better prognosis of the never-smokers. Nevertheless, the high pulmonary/cardiovascular complication-related mortality was another cause of the poor prognosis of the smokers with lung cancer.