Role of Pathological Single- and Multiple-N Descriptors in Resected Non-small Cell Lung Cancer.

BACKGROUND: The 8th edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single- and multiple-N descriptors. RESEARCH QUESTION: Do the single- and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? STUDY DESIGN AND METHODS: Using the National Cancer Database, we analyzed patients with pathologically staged N1-2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pSingle-N2, and pMulti-N2. Survival analysis was performed using Kaplan-Meier method and multivariate Cox regression models. RESULTS: In the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 NSCLC patients had pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2, respectively. Patients with pMulti-N1 and pMulti-N2 had a shorter survival than those with pSingle-N1 and pSingle-N2, respectively (hazard ratio [HR]: 1.22, P < 0.0001 for N1 and 1.39, P < 0.0001 for N2). After adjusting age, sex, and histology, the HR for pSingle-N2 compared with pMulti-N1 was 1.05 (P = 0.0031). Patients with pN1 were categorized by metastatic lymph node count (1, 2, 3, 4+), showing significant prognostic differences among groups (P < 0.0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy or more, survival ≥ 30 days, ≥ 10 examined lymph nodes, and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708) analyses supported these results. INTERPRETATION: NSCLC patients with 1 metastatic lymph node, whether in N1 or N2 stations, had better survival than those with more than 1 lymph node involved. NSCLC patients with a single skip N2 lymph node metastasis had survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to ≥ 4 was sequentially prognostic.

EGFR-mutated lung adenocarcinoma with choroidal oligometastasis during treatment with gefitinib: a case report.

The patient was a 74-year-old woman who was diagnosed with lung adenocarcinoma, clinical Stage IIIA. Induction chemoradiation was performed followed by right upper lobectomy and lymph node dissection. Because of positive pleural effusion cytology, which was proven after surgery, the patient was diagnosed with pathological Stage IVA with EGFR L858R mutation. At 17 months after the administration of gefitinib, left choroidal metastasis appeared. Stereotactic irradiation and ruthenium small-beam radiation were effective; however, the metastatic lesion showed regrowth 7 months after these treatments. Because the patient's choroidal oligometastasis was resistant to conservative therapy, left ophthalmectomy was performed. EGFR mutations (L858R and E709K) were detected in the resected choroidal tumor. The patient continued to take gefitinib. However, a neoplastic lesion developed on the optic nerve adjacent to the resected posterior eye segment. The lesion was treated with stereotactic radiation, gefitinib was switched to afatinib 30 mg, and the patient remains alive and disease free for 11 months.

An analysis of residual lung volume changes after segmentectomy based on three-dimensional computed tomography.

Background: Based on the results of JCOG0802 and CALGB studies, segmentectomy has considered to be a standard procedure for early-stage non-small cell lung cancer (NSCLC). After lobectomy, the residual cavity is filled with mediastinal and diaphragmatic deviations, and compensatory volume changes are present in the residual lungs. In this study, we examined the efficacy of segmentectomy, a surgical procedure, by focusing on its impact on postoperative lung volume and function. Methods: We enrolled 77 patients who underwent segmentectomy as their initial surgical procedure, excluding those with additional lung resections and those who lacked postoperative computed tomography imaging. The predicted residual volume (mL) was defined as the total lung volume before surgery minus the volume of the resected area. Using the predicted residual volume (mL) and postoperative total lung volume (mL), we calculated the rate of postoperative lung volume increase [(postoperative total lung volume/predicted residual volume) × 100] (%). We also classified 52 cases with a rate of postoperative lung volume increase of ≥100% into a compensatory group, while those with a rate of <100% were classified into a non-compensatory group. Results: The average postoperative lung volume increase was 104.6% among 77 cases. Age ≥65 years, pack year index ≥27.5, ≥3 resected segments, and use of electrocautery for intersegmental plane division were significantly associated with compensatory group classification. In 20 compensatory cases with preoperative and postoperative pulmonary function tests, postoperative vital capacity and forced expiratory volume in one second values exceeded the preoperative predictions. This study further examined the areas responsible for postoperative compensatory lung volume increase. In the compensatory group, significant expansion was observed in the ipsilateral lobes, excluding the resected segment and contralateral lung, while no significant changes were noted in the volume of the lobe, including the resected segment. Conversely, the non-compensatory group showed a significant volume decrease in the resected lobe, but no significant increase in other areas. Conclusions: This study emphasizes the importance of preserving lung segments in segmentectomy. The study demonstrates extensive compensatory volume changes in the ipsilateral lung and contralateral lung. There was no significant volume decrease in any residual segment. This underlines the potential of segmentectomy to maintain lung function and expand treatment options post-surgery. In addition, the compensated group included patients with a lower pack-year index and younger patients. These results suggest that postoperative compensatory lung expansion includes not only hyperinflation of the remaining lung, but also an increase in the functional lung parenchyma.

Low FDG uptake in lung metastasis despite high FDG uptake in a primary adenoid cystic carcinoma of a sublingual gland.

Adenoid cystic carcinoma is a rare malignant tumor that primarily occurs in the salivary glands. There are few reports of sublingual gland adenoid cystic carcinoma with lung metastases on which 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) was performed. We report the case of a 57-year-old Japanese woman with an adenoid cystic carcinoma of the sublingual gland with lung metastases in whom the FDG uptake of the lung metastasis was low despite high FDG uptake in the primary lesion. The pathological examination revealed that solid components were more visible and the Ki-67 index was more positive in the primary lesion compared to the metastatic lesion. We speculate that differences in tumor growth ability might have resulted in the differences in FDG uptake. This case demonstrates that significant differences might occur in the FDG uptake between primary and metastatic tumors.

Challenges in Robotic Lung Lobectomy through the Anterior Approach.

PURPOSE: Robot-assisted thoracic surgery (RATS) has become popular because of its minimally invasive nature and reduced burden on surgeons. The anterior approach (AA) is beneficial because it utilizes the same field of view and procedures as thoracotomy and video-assisted thoracic surgery, although the disadvantages are less well-known. METHODS: We retrospectively examined 35 consecutive patients who underwent RATS lobectomy via the AA, focusing on clinical factors and postoperative complications. RESULTS: The study included 12 males and 23 females with a median console time of 177 (120-346) min, median blood loss of 0 (0-100) mL, and median stapler usage of 5 (2-10) units. Postoperative complications, classified as Clavien-Dindo grade ≥III, included three cases of grade IIIa (prolonged air leakage) and one case each of grade IIIb and grade IVa (middle lobe torsion and ventricular arrhythmia). The influence of stapling device operation cannot be ruled out in prolonged air leakage and middle lobe torsion. A moderate correlation (correlation coefficient = 0.492, p = 0.003) was observed between console time and the number of staplers used. CONCLUSION: Although no severe incidence of vascular injury was observed with the AA, complications related to the use of stapling devices were noted.

Osimertinib as first-line treatment for recurrent lung cancer patients with EGFR mutation.

Background: Although osimertinib was approved as adjuvant therapy for lung cancer patients with EGFR mutation in various countries, there is still some ongoing debate as osimertinib has been approved based on disease-free survival (DFS) rather than overall survival (OS). We curated a case series in which we documented patterns of recurrence and efficacy and safety of osimertinib after recurrence. Methods: Patients who received osimertinib as first-line treatment for postoperative recurrence between September 2018 and January 2023 were included. Clinicopathological factors, duration of osimertinib treatment (DoT), and adverse events were collected and analyzed. Results: Twenty patients received osimertinib [male, n=6; median age, 75 years (range, 55-85 years)]. The EGFR mutation type was L858R in 11 patients and exon 19 deletion in eight patients. The performance status (PS) was 0 or 1 in all but two patients, who had symptomatic brain metastasis and were therefore PS 3. The first site of postoperative recurrence was locoregional in five patients and distant in 15 patients, including seven with brain metastasis. As of February 2023, 10 patients were still on osimertinib, including three with brain metastasis. Patients with brain metastasis or poor PS had a considerably shorter DoT than their counterparts. Three patients with symptomatic brain metastasis or leptomeningeal metastasis initially responded to osimertinib, but all died of disease progression. Five patients discontinued osimertinib due to serious adverse effects (pneumonitis, drug eruption, and heart failure). Conclusions: Although osimertinib exerts great disease control, even in patients with brain metastasis or poor PS, their presence was associated with a poor prognosis, even with osimertinib treatment. Therefore, adjuvant osimertinib is recommended unless contraindicated.

Giant benign intrathoracic schwannoma: a decade-long progression towards fatality.

BACKGROUND: Intrathoracic neurogenic tumors arise from sympathetic nerve trunks and intercostal nerves; more than 90% are benign. Schwannomas are the most common histological variety, but fatalities due to giant schwannomas are rare. CASE PRESENTATION: We report a case of a 65-year-old woman who presented with chest pain and cough. Computed tomography (CT) revealed a large left chest wall mass of 130-mm in size, and the patient was referred to our department. Tumor biopsy was performed under local anesthesia, and a diagnosis of schwannoma was made. Ten years previously, a 30-mm tumor had been noted in the left third intercostal space by a previous doctor, but follow-up had been interrupted owing to depressive disorder. Although we planned to perform intercostal artery embolization followed by chest wall tumor resection, the patient did not consent to surgery due to uncontrolled depression. After four months, she developed respiratory failure caused by compression due to an enlarged tumor and died. Autopsy also revealed a benign schwannoma with no malignant findings. CONCLUSIONS: Although schwannomas are benign tumors, there are some very rare cases in which they can become huge and life-threatening. Therefore, a benign tumor should not be neglected, and if surgery is not possible at the time of diagnosis, a regular follow up is necessary, in order not to miss the right timing for surgery.

Significance of programmed death-ligand 1 expression in resected lung cancer and its relationship with EGFR mutation.

BACKGROUND: Several studies have reported that the high expression of programmed death-ligand 1 (PD-L1) within tumor cells predicts a poor prognosis. However, the relationship between the PD-L1 expression and lymph node metastasis or driver mutations in lung cancer remains poorly understood. METHODS: A total of 356 consecutive patients who underwent surgical resection for primary lung cancer were included in the study. There were 268 adenocarcinomas including 100 EGFR mutations, 67 squamous cell carcinomas (Sq), and 21 other histologies. The high expression of PD-L1 was defined as a tumor proportion score (TPS) of ≥50. The relationship between the PD-L1 expression and clinicopathological factors and recurrence-free survival (RFS) was analyzed. RESULTS: The PD-L1 expression was high in 75 patients. It was significantly related to smoking history, Sq histology, driver mutation negative, elevated serum carcinoembryonic antigen levels, and lymph node metastasis. Among patients with driver mutations, a high PD-L1 TPS was found in patients with EGFR G719X mutation. A significant difference in RFS was observed in adenocarcinoma patients. A multivariate analysis of adenocarcinoma cases revealed that tumor size and lymph node metastasis were independent prognostic factors for poor RFS, while the PD-L1 expression was not. A logistic regression analysis revealed that the absence of driver mutations, lymph node metastasis, and a history of smoking were significantly associated with the high expression of PD-L1. CONCLUSION: Lymph node metastasis was positively related with the high expression of PD-L1, resulting in poor RFS. A high PD-L1 TPS was observed in patients with the EGFR G719X mutation.

Cyclin-dependent kinase (CDK) 4/6 inhibition in non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.

BACKGROUND: Lung cancer is the leading cause of cancer death worldwide, and EGFR mutation is the most common genetic alteration among Asian patients with lung adenocarcinoma. While osimertinib has been shown to be effective in lung cancer patients with EGFR mutation, the majority of patients eventually develop acquired resistance to treatment. We explored the significance of the cyclin D1 expression in patients with EGFR mutation and the potential efficacy of adding abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, simultaneously with osimertinib in vitro. MATERIALS AND METHODS: Immunohistochemical staining, using an anti-cyclin D1 antibody, of specimens from 83 patients with EGFR mutation (male, n = 27; pStage 0-I, n = 71) who were treated by surgical resection between 2017 and 2020, and the relationship between the cyclin D1 expression and clinicopathological factors was analyzed. Additionally, the combined effect of osimertinib and abemaciclib in lung cancer cell lines were analyzed using a growth inhibition test, and the signaling pathway underlying the combined effect was investigated. RESULTS: Cyclin D1 was negative in 18.1% of patients with EGFR mutation, and cyclin D1 negativity was associated with pStage ≥ II (p = 0.02), lymph node metastasis (p = 0.001), and lymphatic invasion (p = 0.01). The cyclin D1-negative group had significantly shorter recurrence-free survival (p = 0.02), although this difference disappeared when limited to pN0 patients. In EGFR mutated cell lines, the combination of osimertinib and abemaciclib demonstrated synergistic effects, which were thought to be mediated by the inhibition of AKT phosphorylation. CONCLUSION: Combination therapy with CDK4/6 inhibitors and EGFR-TKIs may be a promising approach.

Tracheal injury from dog bite in a child.

BACKGROUND: Dog bites associated with the head and neck area in children are a common problem. Most of the lacerations are found in the upper lip and the nose region, and tracheal injury is rare [1]. Tracheal injury requires prompt and accurate diagnosis and treatment to rescue the patient. Especially in children, securing the airway is often more difficult than in adults because of their short neck and narrow trachea. In this report, we experienced a pediatric case of multiple dog bites with tracheal injuries in the neck. CASE PRESENTATION: We report the case of a 3-year-old girl who presented with multiple dog bites. There were multiple wounds on the head, face, neck, and anterior chest, and air leakage was observed from the cervical wound at the time of transfer. It was difficult to perform oral endotracheal intubation, therefore, we extended the neck wound, probed the trachea with finger, and inserted a tracheal tube directly from the cervical wound in the emergency room. Tracheoplasty and another wound cleansing were performed in the operating room. The patient was discharged on the 18th day after surgery, without further complications. CONCLUSION: Tracheal injury from a dog bite is rare. It is important to prompt and accurate diagnosis and treatment. Children should be especially careful because of their short necks and narrow tracheas.

Aspergillus Nodule in a Patient With Autoimmune Pulmonary Alveolar Proteinosis.

Although autoimmune pulmonary alveolar proteinosis (APAP) is more likely to be associated with infectious diseases, clinical case-based evidence is too limited to confirm this. We describe a case of a man in his late forties diagnosed with APAP nine years prior to the current presentation. A nodule in the right upper lobe gradually increased from 8 to 12 mm over a period of 6 months and was suspicious of malignancy. The pathological analyses revealed Aspergillus nodule without any malignant features. This study aims to report a case of Aspergillus nodule with APAP and discuss the differential diagnosis of solitary lung nodule developed in APAP.

Clinical significance of part-solid lung cancer in the eighth edition TNM staging system.

OBJECTIVES: The ground-glass component of part-solid tumour (PST) was eliminated as a clinical T (cT) descriptor in the eighth edition of the tumour, node and metastasis (TNM) staging system. We aimed to validate the new cT descriptor and investigate the prognostic impact of PST in the new staging system. METHODS: Non-small-cell lung cancer (NSCLC) patients (n = 1061) who underwent lung resection and were available for the assessment of thin-section computed tomography images were retrospectively reviewed. Tumours with a solid component (SC) size-to-whole tumour size (STR) ratio of 0, those with 0 < STR < 1 and those with an STR of 1 were defined as pure ground-glass tumours, PSTs and solid tumours (STs), respectively. RESULTS: Tumours with an SC diameter of >30 mm were less frequently observed among PSTs than among STs (4.83% vs 32.6%, P < 0.001). The postoperative 5-year survival of NSCLC patients with ground-glass tumour, PST and ST was 97.6%, 89.0% and 76.3%, respectively. In the survival analysis of patients with an SC diameter ≤30 mm, significant differences were observed among PST and ST (5-year survival, 90.7% vs 74.6%, P < 0.001). The multivariable analysis showed that age <70 years old, female sex, procedures with a lobectomy or more, SC size, pN0 disease and PST were independent predictors of a better survival among all PST and ST patients. CONCLUSIONS: Among patients with cT1 tumours, those with PST showed a significantly better survival than did those with ST. Small-sized PST tumours may not be suitable for the new cT descriptor.

Thymoma-associated myasthenia gravis coexisting with myotonic dystrophy: a case report.

BACKGROUND: Myotonic dystrophy (dystrophia myotonica [DM]) is an autosomal-dominant inheritance, and myasthenia gravis (MG) is an autoimmune disease characterized by weakness of skeletal muscles. Cases of both DM and MG are extremely rare and distinguishing DM and MG symptoms is challenging. CASE PRESENTATION: We herein report a 49-year-old woman presenting with subacute dyspnea and muscle weakness. She had previously been diagnosed with DM 24 years earlier. Computed tomography (CT) revealed an anterior mediastinal 32-mm solid mass that was suspected of being thymoma. The clinical features and neurological examination findings confirmed the diagnosis of thymoma-associated MG coexisting with DM. Intensive treatment for MG, including surgery, resulted in an improvement in some of her neurological symptoms. CONCLUSIONS: The symptoms of DM usually progress slowly, so the sudden exacerbation of symptoms indicates the involvement of other factors. It is important to be aware of these associations, as an early diagnosis with proper treatment will result in a better outcome.

Arterial blood supply patterning of the mammary sentinel lymph nodes with special reference to the relation of the formation mechanism of the superficial subscapular artery.

This study aimed to conduct a detailed anatomical examination of the arterial supply to level Ib lymph nodes corresponding to mammary sentinel lymph nodes. This was achieved by focusing on the relationship with course changes of the axillary artery trunk using 41 cadavers (49 axillae). The course patterns of the axillary artery were classified as: "Standard type," which penetrate the brachial plexus (occurrence rate, 51%); "Superficial brachial artery type," which ran along the superficial layer of the brachial plexus (2%); "Superficial subscapular artery (SSbsA) type," which entered the deep layer without penetrating the brachial plexus (42.9%); and others (4.1%). The lateral thoracic artery, thoracodorsal artery, inferior pectoral artery, and superficial thoracic artery were distributed in a regular pair relationship according to each running type of the axillary artery for the Ib lymph nodes. Comparing blood supply ratio to the Ib lymph nodes, using SSbsA occurrence as a reference, showed that significant differences were observed with the inferior pectoral artery control for the standard subscapular artery group and the lateral thoracic artery control for the SSbsA group (p < 0.0001). It was suggested that in selective modeling of vascular networks during upper limb developments, two formation tendencies occur. The standard axillary and SSbsA axillary artery trunks are induced when the inferior pectoral artery-derived feeding arteries in the superficial brachial artery system are selected for Ib lymph nodes, or lateral thoracic artery-derived feeding arteries, which are closely related to the SSbsA pathway, are acquired.

Resection and postoperative radiation therapy for desmoid fibromatosis of the chest wall in a young woman.

BACKGROUND: Surgery is an effective treatment for desmoid fibromatosis, but it may be difficult, depending on the location or local spread of the tumor, and the decision to perform surgery must be made carefully. We herein report a case of desmoid fibromatosis of the chest wall in a young woman suspected of having invasion to the 1st, 2nd and 3rd ribs. CASE PRESENTATION: A 35-year-old woman had been aware of dry cough and right chest pain, so she was referred to our hospital. Chest computed tomography showed a localized pleural tumor mainly at the first rib. Magnetic resonance imaging revealed a 75 × 65 × 27-mm tumor with a smooth surface, with partial contact from the first rib to third rib and partial extension to the 1st intercostal space. The tumor showed growth in the two months after the first visit, so resection was performed. The tumor was completely resected, and adjuvant radiation therapy (50 Gy) was performed for the small margin. The pathological diagnosis was desmoid fibromatosis. The postoperative course has been uneventful, without recurrence at 14 months after surgery. CONCLUSIONS: In chest wall tumors located ventral of the pulmonary apex, we suggest that a combination of the Grunenwald method and Masaoka anterior approach may be a useful option. In cases where margin is not enough, adjuvant radiation therapy should be considered.

Development of diffuse large B-cell lymphoma from duodenal type follicular lymphoma: a retrospective study of 23 cases.

The incidence and clinical characteristics of histological transformation (HT) from duodenal type follicular lymphoma (DFL) are unclear. A retrospective analysis was conducted to identify the incidence and clinical features of HT from DFL in 23 cases with DFL. The median follow-up duration was 4.6 years (range, 0.8-20 years). HT to diffuse large B-cell lymphoma was observed in 2 of 23 cases during follow-up (8.7%). One of two cases transformed at 21 months later with increased serum lactate dehydrogenase (LDH; 1655 U/L) and abdominal lymphadenopathy. Partial response was achieved after R-THP (pirarubicin)-COP therapy, but the disease progressed. The other case transformed at 8.3 years with an increase of serum LDH (4022 U/L), abdominal lymphadenopathy, and bone marrow involvement. The disease was refractory to DA-EPOCH-R and a high-dose methotrexate/cytarabine regimen. The patient received allogenic peripheral blood stem cell transplantation and finally achieved complete response. Both cases developed HT at nodal or other intestinal lesions with no progression of the primary duodenal lesion. No significant factors for the occurrence of HT were identified. Although the incidence is low, HT could occur in DFL with aggressive clinical manifestations.

Evaluating the Platelet Distribution Width-to-Plateletcrit Ratio as a Prognostic Marker for Patients With Breast Cancer.

AIM: This study aimed to evaluate plateletcrit (PCT) and platelet distribution width-to-PCT ratio (PDW/PCT) as potential prognostic biomarkers in patients with breast cancer. PATIENTS AND METHODS: Information of 337 patients was retrospectively reviewed. The Cox regression proportional hazards model was used to evaluate the prognostic value of PCT and PDW/PCT compared to the platelet distribution width-to-platelet count ratio (PDW/P) and red cell distribution width-to-platelet count ratio (RDW/P). RESULTS: Large tumor size (p<0.01), lymph node involvement, and increased PDW/P, RDW/P, and PDW/PCT (p<0.05) were significantly associated with inferior disease-free survival (DFS) according to the univariate analysis. The multivariate analysis showed that large tumor size (p<0.01) and increased PDW/PCT (p<0.05) were significant prognostic factors for poor DFS. CONCLUSION: To our knowledge, this is the first report to show that PDW/PCT is a significant prognostic factor for patients with breast cancer. Therefore, it might be an attractive biomarker providing additional prognostic information for these patients.