Chemotherapy alters subjective senses of taste and smell but not dietary patterns in Japanese lung cancer patients.

PURPOSE: To investigate how outpatient-based chemotherapy would alter the senses of taste and smell and affect daily dietary intake in patients with lung cancer. METHODS: The self-reported taste and smell alteration (TSA) in 35 Japanese patients with lung cancer as well as their patterns of dietary intake at home were tested using a questionnaire. RESULTS: The patients experienced considerable TSA, and smoking was shown to contribute to this alteration. Specifically, current or past smokers were more likely to experience subjective taste change during chemotherapy than never smokers were. Chemotherapy made steamed rice or sushi the most unfavorable food in the patients; on the other hand, Japanese-style noodles were the most preferred during chemotherapy. Nevertheless, the patients maintained their habit of consuming steamed rice at home at least once a day, suggesting the robustness of dietary habits despite the TSA caused by chemotherapy. CONCLUSIONS: Nutritional assessment as well as appropriate advice and intervention by dietitians is expected to improve the general conditions and quality of daily living in patients with cancer.

[Surgical Treatment for Synchronous Double Cancer of the Thoracic Esophagus and Lung].

We herein report 2 cases of radical operation for synchronous double cancer of the thoracic esophagus and each side of the lung. Case 1:A 71-year-old woman with synchronous double cancer of the thoracic esophagus (Mt, T3N2M0, Stage III) and right lung (M, T2aN0M0, Stage I B) underwent esophagectomy concomitantly with right middle lobectomy through right thoracotomy (single-stage operation) after 2 courses of systemic chemotherapy with docetaxel, cisplatin and 5-fluorouracil( DCF regimen). Case 2:A 72-year-old man with synchronous double cancer of the thoracic esophagus( MtLt, T3N2M0, Stage III) and left lung( U, T1aN0M0, Stage I A) underwent 2-stage operation after 2 courses of the DCF therapy. Esophagectomy through right thoracotomy was performed followed by left upper lobectomy through left thoracotomy 3 months later. Treatment strategy for synchronous double cancer of the thoracic esophagus and lung is discussed based on our experiences and previous reports.

[Displaced B1+2 Found at Video Assisted Thoracic Surgery for Lung Cancer of Left Upper Lobe].

We report the case of an 83-year-old woman who presented with an abnormal pulmonary nodule suspected to be lung cancer in the left S3 segment. Bronchoscopy showed that the left main bronchus branched off into the B1+2, B3 plus lingular bronchus, and lower bronchus. Video-assisted thoracic surgery was performed, and the nodule was pathologically diagnosed as a primary lung cancer. Subsequently, left upper lobectomy was performed, and an abnormal bronchus was observed behind the main pulmonary artery. Intraoperative bronchoscopy indicated that the bronchus was the displaced B1+2. The B3 plus lingular bronchus existed at the common place of the upper bronchus. The displaced B1+2 and the other upper bronchus were transected separately. No other abnormalities were observed in the pulmonary arteries, veins, or bronchi. Preoperative examination is the best way to detect this bronchial abnormality;identification with intraoperative bronchoscopy can play a crucial role in determining the perioperative strategy.

[Independent Occurrence of a Mediastinal Bronchogenic Cyst and an Intralobar Pulmonary Sequestration].

Here we describe a case of an 18-year-old boy who exhibited abnormal pulmonary parenchyma supplied by an aberrant artery from the descending aorta in the right lower lobe of the lung and a cystic tumor measuring 34×26×54 mm in the right upper mediastinum. Video-assisted thoracic surgery for resection of the 2 lesions showed that they were independent of each other. Final diagnosis of an intralobar pulmonary sequestration in the right lower lobe and a bronchogenic cyst in the upper mediastinum was made. In some reports, 2 lesions were described to be in close proximity to and connected with each other, but the present case is unique in that the 2 lesions were completely independent of each other.

Spontaneous hemopneumothorax: epidemiological details and clinical features.

PURPOSES: Spontaneous hemopneumothorax (SHP) may cause life-threatening blood loss. The objective of this study was to elucidate the epidemiological and clinical features of SHP. METHODS: We reviewed the records of 26 patients who underwent surgery for SHP between 1989 and 2010. We evaluated their epidemiology and clinical features by comparing them with those of 681 patients with spontaneous pneumothorax treated during the same period. RESULTS: The proportion of smokers in the SHP group was higher than that in the spontaneous pneumothorax group (P < 0.01). Seventeen cases (65.4 %) of SHP occurred on the left side. The most frequent bleeding area was the superior thoracic aperture (STA:17 cases, 65.4 %), followed by the left superior mediastinum (six cases, 23.1 %). Ten cases had intrathoracic clots greater than 500 mL, which could not be drained preoperatively. The postoperative stay of patients treated with video-assisted thoracic surgery (VATS) was shorter than that of patients treated with open thoracotomy (21 versus five cases; P < 0.05). CONCLUSIONS: A higher proportion of smokers was revealed in the SHP patients. VATS shortened the hospital stay of the patients. The particular areas that should be observed intraoperatively are the STA and the left superior mediastinum.

Real Clinical Practice of Combined Atezolizumab Plus Chemotherapy in Patients With Small Cell Lung Cancer.

BACKGROUND/AIM: Atezolizumab, an anti-PD-L1 antibody, has been increasingly administered in combination with chemotherapy to patients with small cell lung cancer (SCLC). This study aimed to determine how patients with extensive disease (ED) -SCLC responded to atezolizumab with chemotherapy and found factors affecting long-term response and survival. PATIENTS AND METHODS: This study focused on patients with SCLC who were treated with a combination of atezolizumab and chemotherapy in Japan between 2019 and 2023. Patient information and tumor response were analyzed, along with adverse events. We compared data and estimated survival probabilities. RESULTS: In our clinical trial, 95 patients with SCLC who received this treatment had a median progression-free survival of 6.0 months and a median overall survival of 15.0 months. Immune-related adverse events were observed in 13.7% of the patients, with grade 3 or higher in 5.3%. The efficacy and immune-related adverse events associated with this treatment regimen were comparable to those reported in previous clinical trials. Progression-free survival >2 years was observed in a small number of patients (5.3%). CONCLUSION: Our research will offer important insights for the future care of patients with extensive-stage SCLC by utilizing atezolizumab in combination with chemotherapy. Accumulation and confirmation of clinical practice results will have important implications for the future implementation of this therapy.

Identification of the Separation Range of an Incomplete Interlobar Fissure in Segmentectomy Using Near Infrared.

In segmentectomy for patients with incomplete interlobar fissures, insufficient dissection of the interlobar parenchyma may result in incomplete segmentectomy, while excessive dissection may lead to excessive bleeding and air leaks. Here, we report a case of left apicoposterior (S1+2) segmentectomy with incomplete interlobar fissure in which near-infrared thoracoscopy with indocyanine green was used to identify the separation range of interlobar fissure by dissecting the relevant vessels beforehand.

Atezolizumab Monotherapy for Non-small Cell Lung Cancer Patients: An Observational Study in Ibaraki Group (ATTENTION-IBARAKI).

BACKGROUND/AIM: Atezolizumab is a monoclonal antibody that targets programmed death-ligand 1 (PD-L1) expressed on cancer cells derived from various organs and antigen-presenting cells and is currently commonly used in combination with chemotherapy. We conducted a study to clarify the current status of response to atezolizumab monotherapy in clinical practice and clarify the factors that contribute to long-term response and survival. PATIENTS AND METHODS: We conducted a retrospective review of patients with advanced non-small cell lung cancer (NSCLC) treated with atezolizumab monotherapy from April 2018 to March 2023 at 11 Hospitals. RESULTS: The 147 patients evaluated had a progression-free survival (PFS) of 3.0 months and an overall survival of 7.0 months. Immune-related adverse events of any grade were observed in 13 patients (8.8%), grade 3 or higher in nine patients (6.1%), and grade 5 with pulmonary toxicity in one patient (0.7%). Favorable factors related to PFS were 'types of NSCLC other than adenocarcinoma'. Favorable factors for overall survival were 'performance status 0-1' and 'treatment lines up to 3'. There were 16 patients (10.9%) with PFS >1 year. No characteristic clinical findings were found in these 16 patients compared to the remaining 131 patients. CONCLUSION: Efficacy and immune-related adverse events of NSCLC patients associated with atezolizumab monotherapy were comparable to those of previous clinical trial results. Knowledge of characteristics of patients who are most likely to benefit from atezolizumab monotherapy is a crucial step towards implementing appropriate prescribing.

Atezolizumab for EGFR-mutated Non-small Cell Lung Cancer Patients: An Observation Study in Ibaraki Group (ATTENTION-IBARAKI).

BACKGROUND/AIM: Atezolizumab, an anti-programed death-ligand 1 monoclonal antibody, targets programed death-ligand 1 expressed on cancer cells and antigen-presenting cells and is now commonly used in combination with chemotherapy. We conducted a study to clarify the efficacy of atezolizumab in epidermal growth factor receptor (EGFR)-mutated patients who are considered less responsive to immune checkpoint inhibitors. PATIENTS AND METHODS: A retrospective review of patients with advanced non-small cell lung cancer (NSCLC) who received atezolizumab-containing therapy at 11 hospitals from April 2018 to March 2023 was performed. RESULTS: Median progression-free survival and overall survival in 33 EGFR-mutated patients treated with atezolizumab monotherapy were 2.0 and 9.0 months, respectively, and those in 19 patients who received combined atezolizumab plus chemotherapy were 12.0 and 17.0 months, respectively. When comparing EGFR-mutated and EGFR-negative patients after propensity score matching, there were no significant differences in progression-free survival and overall survival between the two groups, whether atezolizumab monotherapy or combined atezolizumab plus chemotherapy. Among EGFR-mutated patients, being male was a significant favorable factor in both atezolizumab treatment groups. None of the EGFR-mutated patients had grade 5 immune-related adverse events. CONCLUSION: Efficacy of atezolizumab in EGFR-mutated NSCLC patients could be comparable to that for EGFR-negative patients. To prolong the survival of EGFR-mutated NSCLC patients, appropriate selection and sequencing of EGFR for tyrosine kinase inhibitors, as well as immune checkpoint inhibitors, anti-tumor agents, and anti-angiogenic agents are important.

Prognostic Implication of PD-L1 Expression on Osimertinib Treatment for EGFR-mutated Non-small Cell Lung Cancer.

BACKGROUND/AIM: Real-world data on the clinical outcomes of first-line osimertinib treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations is lacking. This study aimed to reveal the treatment outcomes and prognostic factors of osimertinib as first-line therapy in clinical practice settings. PATIENTS AND METHODS: We retrospectively evaluated clinical outcomes of patients with EGFR-mutated NSCLC treated with osimertinib as first-line therapy across 12 institutions in Japan between August 2018 and March 2020. RESULTS: Among 158 enrolled patients, the objective response rate (ORR) was 68%, and the estimated median progression-free survival (PFS) was 17.1 months [95% confidence interval (CI)=14.5-19.7]. Subgroup analysis showed that PFS in the group with high programmed death-ligand 1 (PD-L1) expression was significantly shorter than that in groups with low or no PD-L1 expression (10.1 vs. 16.1 vs. 19.0 months; p=0.03). Univariate and multivariate analyses demonstrated that high PD-L1 expression was the only independent adverse prognostic factor of osimertinib outcome related to PFS (hazard ratio=2.71; 95%CI=1.26-5.84; p=0.01). In terms of anti-tumor response, there was no statistically significant correlation between PD-L1 expression and the ORR (67% vs. 76% vs. 65%; p=0.51). No significant correlation was also found between PD-L1 and the incidence of de novo resistance to osimertinib (p=0.39). CONCLUSION: Although PD-L1 expression was not associated with either the ORR or frequency of de novo resistance, high PD-L1 expression could be an independent adverse prognostic factor related to PFS in osimertinib treatment.

Guide sheath breakage during endobronchial ultrasonography.

This report describes a case of guide sheath breakage during endobronchial ultrasonography. While steering the guide sheath in the direction of a peripheral lung nodule using a guiding device/curette, the radiopaque band (RB) attached to the head of the guide sheath dislodged and remained in the peripheral bronchus near the tumour. The band could not be removed endoscopically. As the tumour was diagnosed as a colon cancer metastasis, we performed a partial lung resection to remove the RB and nodule together four months after bronchoscopy.

A population-based study of outcomes in patients with surgically resected non-small cell lung cancer with anaplastic lymphoma kinase-rearranged mutations: A matched-pair study.

The present study aimed to evaluate clinical outcomes in patients with surgically resected non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearranged mutations. A matched-pair analysis in completely resected ALK-rearranged NSLC patients and those with neither ALK nor epidermal growth factor receptor (EGFR) mutations diagnosed at 11 institutes was performed between April 2008 and March 2019. A total of 51 patients with surgically resected ALK-rearranged NSCLC were included. Women constituted 68.6%, and smokers 29.4%. The median age was 65 years. In matched-pair analysis, disease-free survival and overall survival did not differ between patients with ALK-rearranged mutations and those without mutations. Post-recurrence survival in patients with ALK mutations was longer than that of patients with neither ALK nor epidermal growth factor receptor mutations. ALK genetic testing should be performed, even in elderly patients with NSCLC. Favorable prognosis might be expected after appropriate treatment for patients with recurrent ALK-mutated disease.

Expression of phosphorylated Akt in patients with small cell carcinoma of the lung indicates good prognosis.

Patients with pulmonary small cell carcinoma are well known to have a poor prognosis. However, predictors of prognosis and treatment outcome have not been reported for this type of cancer. We examined whether excision repair cross-complementation group 1 (ERCC1), phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and the uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genetic polymorphism were useful indicators of prognosis in cases of small cell carcinoma of the lung. We investigated 45 patients with advanced small cell lung cancer who received chemotherapy with irinotecan combined with cisplatin or carboplatin. Staining results showed that 12 of 45 cases (27%) were positive for p-Akt, while 18 (40%) were positive for p-mTOR and 16 (36%) were positive for ERCC1. As for UGT1A1, more than one polymorphism was found in 30 cases (67%). There was a significant relationship observed between the expressions of p-Akt and p-mTOR (P= 0.0006). Univariate analysis indicated a significantly better survival rate for patients positive for p-Akt or p-mTOR, while multivariate analysis using a Cox test showed p-Akt to be the strongest prognostic factor. Our results indicate that p-Akt is a reliable prognostic factor in patients with small cell carcinoma of the lung.

[Detection of ALK positive pulmonary adenocarcinoma using immunostaining].

Although ALK-positive lung cancer cases have been recently reported, it is impossible to detect using only morphology technique. Furthermore, though RT-PCR and FISH techniques can be used for detection, they are not practical for screening. We investigated whether ALK-positive lung cancer could be detected using a conventional immunostaining method. Resected lung adenocarcinoma samples from 88 nonsmoker cases were selected and screening was performed using ALK immunostaining in 24 cases that did not have the EGFR or k-ras mutation. We found that the optimal staining condition was treatment using a water bath and detection with a Novo Link Polymer Detection System (Leica microsystems). Of the 24 cases examined, ALK expression was found in 4, of which ALK separated signals were found in 3 using a FISH method. No separated signals were seen in cases with negative immunostaining findings. Detection by immunostaining was found useful for ALK mutated lung cancer cases, though the pretreatment and detection methods utilized are important.

Treatment of Patients With Non-small-cell Lung Cancer With Uncommon EGFR Mutations in Clinical Practice.

BACKGROUND/AIM: To describe real clinical outcomes in patients with non-small cell lung cancer who have uncommon epidermal growth factor receptor (EGFR) mutations. MATERIALS AND METHODS: We performed a retrospective chart review from 15 medical institutes that cover a population of three million people from April 2008 to March 2019. RESULTS: There were 102 patients with uncommon EGFR mutation. Progression-free survival (PFS) tended to be longer in patients receiving afatinib compared with first-generation EGFR tyrosine kinase inhibitors. PFS in patients treated with afatinib or osimertinib was significantly longer than in patients treated with gefitinib or erlotinib (p=0.030). Multivariate analysis also revealed the contribution of afatinib or osimertinib to increased survival. In patients with exon 20 insertions, chemotherapy was efficacious. CONCLUSION: In treating patients with uncommon EGFR mutations, our results indicate longer-term survival might be achieved with second-generation or later TKIs and cytotoxic chemotherapeutic drugs.

Real Clinical Practice in ALK-rearranged NSCLC Patients: A Retrospective Observational Study.

BACKGROUND/AIM: To describe real clinical outcomes when using systemic therapy to treat non-small cell lung cancer (NSCLC) patients who have anaplastic lymphoma kinase (ALK) fusion gene mutation. PATIENTS AND METHODS: We performed a retrospective chart review from April 2008 to March 2019 sourced from 16 medical institutes that cover a population of three million people. RESULTS: There were 129 ALK rearranged NSCLC patients. Among them, 103 patients including 40 recurrent disease cases received ALK-tyrosine kinase inhibitors (TKI) and chemotherapy. Our treatment results were comparable to previously reported clinical trials and clinical practice studies. First-line alectinib, treatment sequence of ALK-TKI followed by another ALK-TKI, and pemetrexed-containing chemotherapy contributed to the outcome of treatment. CONCLUSION: By arrangement of treatment such as treatment sequence of ALK-TKI and chemotherapy regimen, it might be possible to obtain a treatment outcome almost equivalent to those of clinical trials even in real clinical practice.

A population-based study of gefitinib in patients with non-small cell lung cancer.

Survival data for non-small cell lung cancer is typically reported from clinical trials that include patients fit enough to meet treatment criteria. The denominator of all patients from which the gefitinib-treated population is derived has rarely been reported and the impact of gefitinib on population-based outcomes is difficult to measure. We have retrospectively reviewed data of 626 patients who received gefitinib in Ibaraki Prefecture (with a population of 3 million) in Japan from July 2002 until September 2007. Overall response rate was found to 30.8%, and the median survival time was 8.0 months (95% confidence interval: 7.0-9.0 months). Female gender, good PS, and adenocarcinoma were significantly associated with prolonged survival. Adverse events were generally mild and were mostly skin reactions and diarrhea. Our population-based study has generated similar results to those previously reported in published clinical trials, which had restrictive criteria for eligible patients.

Rapid detection of matrix metalloproteinase-7 and carcinoembryonic antigen mRNA expression in intraoperative pleural lavage samples using the reverse transcriptase loop-mediated isothermal amplification method.

OBJECTIVE: To detect the RNA of the tumor origin in intraoperative pleural lavage accurately by examining using rapid nucleic acid amplification method because patients with lung cancer often have recurrence detected by a cytologic examination of cancer cells in intraoperative pleural lavage. STUDY DESIGN: We used reverse transcriptase loop-mediated isothermal amplification (RT-LAMP), which enables rapid gene amplification, and examined the expression of matrix metalloproteinase-7 (MMP-7) and carcinoembryonic antigen (CEA) mRNA in intraoperative pleural lavage samples obtained from 79 consecutive surgical patients with lung adenocarcinoma. RESULTS: MMP-7 mRNA was detected in cancer tissues from 76 (96%) of those cases, while it was also detected in the intraoperative pleural lavage samples of 23 (30%) of those 76 cases. In addition, CEA mRNA was detected in cancer tissues from 55 (70%) cases and in 8 (15%) of the lavage samples. MMP-7 mRNA-positive cases showed a significantly positive correlation with the p and n factors, and moderate to poor differentiation. Three cases shown to be positive in cytology examinations were also positive for both MMP-7 and CEA mRNA by RT-LAMP. CONCLUSION: This detection method can be utilized during an operation and may provide useful information.

[S-1 activity in non-small cell lung cancer in clinical practice].

OBJECTIVE: We evaluated retrospectively single-agent S-1 chemotherapy in non-small cell lung cancer patients in clinical practice. METHODS: Sixteen consecutive patients treated with single-agent S-1 for NSCLC between July 2005 and June 2007 at the Department of Thoracic Surgery, Tsuchiura Kyodo General Hospital. The treatment schedule comprised oral administration of S-1 at 80-120 mg/day. One cycle of S-1 consisted of consecutive administration to 14 (10 cases)or 28(6 cases)days followed by a 14-day rest. RESULTS: Patients profiles were: M/F: 11/5, median age 68 years old(range 51-83), PS 0/1/2/3: 2/6/5/3, adeno/squamous/large: 13/2/1, clinical stage 3A/3B/4: 3/4/9, prior chemotherapy regimens 0/1/2/3/4: 2/3/4/5/2, prior surgery/radiation: 12/5 were performed. Median number of delivered cycles was 5 cycles(range 1-13). Grade 3 hematological toxicities were anemia(6%)and thrombocytopenia(6%). Grade 3 non-hematological toxicities were nausea(6%)and vomiting(6%). Response of 13 patients could be evaluated after 2-4 cycles of S-1. Four partial responses were observed, for a response rate of 31%. The survival time was 67-852 days(average 14.0 months), 1-year survival rate was 74.0%, median time to progression was 4.6 m, and 1- year progression free survival was 25.0%. CONCLUSION: Single-agent S-1 chemotherapy has modest activity and is the one of the important regimens and tolerable for elderly, poor-PS, recurrent patients with NSCLC in clinical practice.