Treatment-related adverse events of combination chemoimmunotherapy versus chemotherapy alone in first-line treatment for non-small cell lung cancer: a systematic review and meta-analysis of randomized clinical trials.

Background: Numerous meta-analyses have examined immunotherapy-induced adverse events (AEs) in non-small cell lung cancer (NSCLC). However, there is limited research comparing AEs from combination chemoimmunotherapy versus chemotherapy alone in the first-line NSCLC treatment, particularly regarding specific toxic symptoms and hematological toxicities associated with the addition of immune checkpoint inhibitors (ICIs). Methods: We conducted a meta-analysis of randomized clinical trials (RCTs) comparing ICIs + non-ICIs versus non-ICIs alone as first-line therapy in NSCLC, sourced from PubMed and Scopus databases. Our objective was to assess treatment-related AEs in both regimens, focusing on identifying the more prevalent toxic symptoms and hematological toxicities with ICI treatment. We calculated the relative risks (RRs) and 95% confidence intervals (CIs), and estimated the pooled RRs and 95% CIs using common- or random-effects models. Results: Our analysis included 10 trials with 6,008 patients. Combination chemoimmunotherapy significantly increased the risk of grade 3 or higher treatment-related AEs, treatment discontinuation, and deaths due to treatment-related AEs. Moreover, patients receiving combination chemoimmunotherapy had a significantly higher risk of certain toxic symptoms (all-grade: vomiting, diarrhea, and constipation; high-grade: fatigue and diarrhea) and pneumonitis (both all-grade and high-grade). Conclusions: These findings offer crucial insights into the toxicity profile of combination chemoimmunotherapy, serving as a valuable resource for clinicians managing lung cancer care.

Association between sex and outcomes in patients with non-small-cell lung cancer receiving combination chemoimmunotherapy as a first-line therapy: a systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: Recently, several meta-analyses have investigated the association between sex and the efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC). However, this issue remains controversial, because the results have been inconsistent. Moreover, the effect of sex on outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy is poorly understood. The aim of this study was to examine the association between sex and outcomes in patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy. METHODS: We searched PubMed and Scopus from database inception to Feb 18, 2022 and performed a systematic review and meta-analysis of randomized and controlled clinical trials investigating ICI+non-ICI vs non-ICI as a first-line therapy in NSCLC. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) in male and female patients were calculated using common and random-effects models. RESULTS: We analyzed 5,830 patients, comprising 4,137 (71.0%) males and 1,693 (29.0%) females, from nine randomized clinical trials. The pooled HR (95%CI) for OS comparing ICI+non-ICI vs non-ICI was 0.80 (0.72-0.87) for males and 0.69 (0.54-0.89) for females. The pooled HR (95%CI) for PFS comparing ICI+non-ICI vs non-ICI was 0.60 (0.55-0.66) for males and 0.56 (0.44-0.70) for females. CONCLUSIONS: In patients with NSCLC receiving combination chemoimmunotherapy as a first-line therapy, a greater improvement in OS and PFS was observed in female patients than in male patients.

An Adult Case of Multiple Extralobar Pulmonary Sequestrations in the Thoracic and Abdominal Cavities.

Extralobar pulmonary sequestration is generally located in the left thoracic cavity and is often identified prenatally or in infants. We identified a rare case of multiple extralobar pulmonary sequestrations in the thoracic and abdominal cavities, incidentally detected in a 60-year-old woman by cancer screening. The patient underwent surgery by thoracoscopic and laparoscopic approaches simultaneously, and extralobar sequestration was histologically confirmed in each lesion. Preoperative diagnosis was difficult because of unusual multiple localization and an undetectable aberrant artery on imaging examinations.

Unexpected Histopathological Diagnosis of Placental Transmogrification of the Lung after Bullectomy for Recurrent Spontaneous Pneumothorax: A Case Report and Literature Review.

We report a 33-year-old man who presented with recurrent right pneumothorax. Computed tomography (CT) showed the presence of a large bulla with a maximum diameter of 8 cm in the right middle lobe; he subsequently underwent bullectomy. Histopathology revealed that pulmonary parenchyma adjacent to the bulla represented nodular proliferation of clear cells characterized by a papillary structure resembling placental chorionic villi. Immunohistochemically, clear cells were positive for CD10, suggesting placental transmogrification of the lung (PTL). We reviewed 36 surgical cases of PTL, and only 2 cases (5.6%), including our case, were operated for spontaneous pneumothorax. Bullous lesions secondary to PTL tend to appear as unilateral large cystic masses in non-upper lobes, which is atypical for primary spontaneous pneumothorax (PSP). Although PTL is considered a very rare cause of secondary pneumothorax, we must carefully differentiate this condition.

Mutual checking system for assessing trainee skills of thoracic surgery.

BACKGROUND: Video-assisted surgery helps surgeons learn surgical skills efficiently. The aim of this study was to evaluate the effect of mutual evaluation of trainees' surgical techniques using tabulated common evaluation criteria. METHODS: We created a check sheet in which a standard pulmonary lobectomy procedure was divided into six parts and the checkpoints to note listed. Both the trainees and trainers used tabulated common evaluation criteria to evaluate lobectomies performed by the trainees. RESULTS: From September 2019 to March 2020, 30 lobectomies were performed by three trainees. The trainee's evaluations of their own procedures were relatively high at first, then decreased, then gradually increased; however, the trainers' evaluations showed no such tendency. CONCLUSIONS: Mutual evaluation of surgery using tabulated common evaluation criteria enables trainees to review their own surgery objectively and receive evaluations by trainers, thus helping them to avoid the Dunning-Kruger effect and efficiently acquire basic surgical skills.

VATS right apical segmentectomy for lung cancer in a patient with tracheal bronchus.

INTRODUCTION: A tracheal bronchus is rarely observed, occurring in only 1% of all patients who undergo thoracic surgeries. We rarely encounter lung cancer in a patient with a tracheal bronchus; however, it is essential to know the distinctive perioperative management strategy for patients with a tracheal bronchus. CASE PRESENTATION: We report a 72-year-old man with lung cancer located in the right apical segment supplied by a tracheal bronchus. Annual chest computed tomography performed as follow-up after colon cancer resection showed an enlarging pulmonary nodule with pure ground-glass opacity, which was suspected to be lung adenocarcinoma. The nodule was located in the right apical segment. The apical segment was independently supplied by a single pulmonary artery superior trunk and a tracheal bronchus that branched directly from the trachea at 1.2 cm above the carina. The pulmonary vein branching pattern was uncommon in that the central vein that usually runs through B2 (posterior bronchus) and B3 (anterior bronchus) was missing. The patient underwent video-assisted thoracoscopic apical segmentectomy under one-lung ventilation using a left-sided double-lumen tube. DISCUSSION: Anomalous venous return accompanied with tracheal bronchus has been described in some reports. Since pulmonary vein is important during segmentectomy, the surgeon should pay particular attention to the venous return. CONCLUSION: Preoperative three-dimensional graphic imagery helped us accurately identify the anatomical anomaly to enable the successful segmentectomy in a patient with a tracheal bronchus. We review the relevant literature regarding the perioperative management of patients with a tracheal bronchus.

Assessment of Intraoperative Microbiological Culture in Patients with Empyema: Comparison with Preoperative Microbiological Culture.

PURPOSE: Assessing microbiological culture results is essential in the diagnosis of empyema and appropriate antibiotic selection; however, the guidelines for the management of empyema do not mention assessing microbiological culture intraoperatively. Therefore, we tested the hypothesis that intraoperative microbiological culture may improve the management of empyema. METHODS: We performed a retrospective analysis of 47 patients who underwent surgery for stage II/III empyema from January 2011 to May 2019. We compared the positivity of microbiological culture assessed preoperatively at empyema diagnosis versus intraoperatively. We further investigated the clinical characteristics and postoperative outcomes of patients whose intraoperative microbiological culture results were positive. RESULTS: The positive rates of preoperative and intraoperative microbiological cultures were 27.7% (13/47) and 36.2% (17/47), respectively. Among 34 patients who were culture-negative preoperatively, eight patients (23.5%) were culture-positive intraoperatively. Intraoperative positive culture was significantly associated with a shorter duration of preoperative antibiotic treatment (p = 0.002). There was no significant difference between intraoperative culture-positive and -negative results regarding postoperative complications. CONCLUSIONS: Intraoperative microbiological culture may help detect bacteria in patients whose microbiological culture results were negative at empyema diagnosis. Assessing microbiological culture should be recommended intraoperatively as well as preoperatively, for the appropriate management of empyema.

Spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer: a case report and literature review.

We report a 69-year-old woman with spontaneous pneumothorax associated with cavitating pulmonary metastasis from breast cancer. She was treated for right breast cancer (invasive ductal carcinoma, ypT4bN1M0, stage IIIB) 2 years earlier, and was admitted for right pneumothorax and chest computed tomography, which showed multiple small cavitating lesions in bilateral lungs. The pneumothorax was treated conservatively with chest drainage, but subsequently recurred ipsilaterally. During video-assisted thoracic surgery, we detected small white nodules with visceral pleural rupture; therefore, we performed partial lung resection. The pathological findings revealed metastatic breast cancer with pleural invasion. Forty days later, ipsilateral pneumothorax recurred, and chemical pleurodesis was performed, which resolved the pneumothorax and prevented subsequent recurrence. Early diagnosis and definitive treatment, including pleurodesis, should be considered to prevent recurrence of spontaneous pneumothorax and improve patients' quality of life, even in patients with advanced malignancy.

Interpleural distance predicts persistent air leak after initial primary spontaneous pneumothorax.

BACKGROUND: Initial surgical intervention for a first episode of primary spontaneous pneumothorax (PSP) is controversial. However, if air leak persists after initial drainage, surgical treatment is recommended. Therefore, we investigated risk factors for persistent air leak (PAL) in patients with a first episode of PSP. METHODS: We retrospectively analyzed 122 patients with a first episode of PSP between January 2011 and April 2019. PAL was defined as air leak lasting 72 hours or longer. Early admission was defined hospital admission within 24 hours of symptom onset. Three methods were used to estimate pneumothorax size on chest X-rays taken at admission: interpleural distance, apex-cupola distance, and Light index. RESULTS: Among 122 patients, 55 developed PAL (PAL group) and 67 did not (non-PAL group). The size of pneumothorax was significantly larger in the PAL group than in the non-PAL group in all three methods of assessment (P<0.001). Early hospital admission was significantly associated with PAL (P=0.026). Logistic regression analysis revealed that the odds ratio for PAL per unit increase in pneumothorax size evaluated with the interpleural distance was 1.304 (P<0.001). Multivariate logistic regression analysis showed that interpleural distance at the hilum and early admission (P<0.001, P=0.008, respectively) were independent predictors of PAL in patients with a first episode of PSP. CONCLUSIONS: In our study, we demonstrated that the interpleural distance at the hilum is a simple and effective predictor of PAL in patients with a first episode of PSP. Our data may help decision-making for initial surgical treatment in these patients.

[Retrospective Examination of Usefulness and Adverse Effects of Tapentadol in Patients with Cancer Pain during Anticancer Treatment].

We retrospectively examined 106 cases of tapentadol use in Japan in August 2014 for cancer pain at our hospital.The advantage of the opioid medication tapentadol is that its introduction is suitable in patients undergoing anti-cancer treatment because of the low incidence of gastrointestinal symptoms, with glucuronidation involved in the metabolism, and lack of interactions with other drugs.However, depending on the dosage form and presence of swallowing disorders, the administration should be considered carefully.

An autopsy case of bird-related chronic hypersensitivity pneumonitis presenting with repeated acute exacerbation.

A 68-year-old woman was admitted to our hospital with a dry cough in 2010. Chest computed tomography showed the appearance of a nonspecific interstitial pneumonia (NSIP) pattern. Video-assisted thoracoscopic surgery (VATS) was performed, and the specimens prominently showed a usual interstitial pneumonia (UIP) pattern. She was diagnosed with bird-related chronic hypersensitivity pneumonitis (BRCHP) on the basis of the detection of antibodies to pigeon dropping extract in her serum and a history of using feather-filled duvets and indirect exposure to birds in her living environment. Even though she was treated with corticosteroids and immunosuppressants and recommended to avoid bird-related antigens, she had a progressive course with repeated acute exacerbation episodes and died of respiratory failure. The autopsy findings showed diffuse alveolar damage superimposed on UIP. Clinicians should be aware that BRCHP patients especially with histopathologically UIP pattern may experience acute exacerbation.

[A New Twist on the Administration of Naldemedine for Opioid-Induced Constipation in an Outpatient].

Opioid-induced constipation(OIC)occurs with high frequency in patients with cancer undergoing pain treatment using opioids. Osmotic or irritant laxatives are usually used to prevent OIC. Recently, naldemedine has become operational for OIC. Although naldemedine achieved the desired effect, diarrhea is a little feared from the results of clinical phase III study(V9236 clinical trial). We herein report the use of naldemedine to alleviate diarrhea and expect the improvement of the quality of the bowel habits in outpatients with cancer undergoing pain treatment using opioids.

[Combinatorial Use of Rapid-Onset Opioid and Short-Acting Opioid Is Effective against Breakthrough Cancer Pain].

Breakthrough cancer pain is divided into "predictable breakthrough pain" and "unpredictable breakthrough pain". Uncontrolled breakthrough pain in cancer negatively affects the quality of life of the patients. The short-acting opioid(SAO) requires considerable time to produce analgesia, and is not adequate as a rescue drug. The rapid-onset opioid(ROO)immediately produces analgesia, but its appropriate usage is difficult. For instance, the frequency and interval of ROO usage is limited, making the optimization of dosage cumbersome. Therefore, ROO has not yet gained popularity. Here, we report that a combinatorial use of ROO and SAO is effective against breakthrough cancer pain, with SAO and ROO being suitable for "predictable breakthrough pain", and "unpredictable breakthrough pain", respectively. The effectiveness and safety of this combination were assessed for many patients with breakthrough cancer pain.

Initial Experience of Single-Incision Thoracoscopic Surgery for 100 Patients with Primary Spontaneous Pneumothorax.

PURPOSE: The aim of this retrospective study was to evaluate single-incision thoracoscopic surgery (SITS) for primary spontaneous pneumothorax (PSP). METHODS: Among 141 patients who underwent surgery for PSP from July 2009 to December 2013, a total of 100 patients underwent SITS. Their data were examined for clinical characteristics and surgical results. RESULTS: More patients with younger age, female sex, and who had social indications were treated by SITS than by three-port video-assisted thoracic surgery (VATS). The mean operative time for SITS was 48.8 min. There were no conversions from SITS to three-port VATS or thoracotomy. After SITS, the median duration of chest drainage was 1 day, and the median hospital stay was 2 days. Early complications included one surgical-site infection and one case of air leakage. Four patients (4.0%) had ipsilateral recurrence of PSP. CONCLUSION: SITS is feasible when performed for selected patients with PSP. Long-term follow-up and further examinations are required to evaluate patient selection, efficacy, and comparability of SITS with conventional open and three-port VATS approaches.

Diaphragmatic hernia caused by heterotopic endometriosis in Chilaiditi syndrome: report of a case.

A 50-year-old Japanese female was admitted to our hospital because of ileus due to Chilaiditi syndrome. Her symptoms did not improve with conservative therapy, so chest and abdominal computed tomography (CT) was performed on the fifth day after hospital admission. A diagnosis of incarceration of a right diaphragmatic hernia was established in the coronal view of CT, and emergency surgery was performed. A dilated loop of small intestine was seen in the right thoracic cavity, which was strangulated by the 2-cm defect in the diaphragm. Primary closure of the diaphragm was performed. Approximately 80 cm of the terminal ileum showed obvious ischemic changes, and it was cut and reconstructed. Postoperatively, the patient made an uneventful recovery and was discharged on the 15th postoperative day. A histological examination of the specimen of the diaphragm around the hernia orifice showed the presence of a small cystiform glandular system with hemorrhage and congestion. These findings indicated that heterotopic endometriosis was present in the diaphragm. This report describes the first known case of right diaphragmatic hernia secondary to heterotopic endometriosis in a patient with Chilaiditi syndrome. The clinical course and management of affected patients and a literature review of these three unusual conditions are discussed.