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.

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.

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.

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.

Ciliated muconodular papillary tumor of the lung: a case report and literature review.

Ciliated muconodular papillary tumor (CMPT) of the lung is characterized as a peripheral low-grade malignant tumor with ciliated columnar cells and goblet cells with basaloid cell proliferation. Herein, we report on a case of CMPT with a radiologically abnormal shadow which was reminiscent of adenocarcinoma. The patient underwent right S6 + S8a segmentectomy because an intraoperative biopsy suggested CMPT, the malignancy of which was difficult to distinguish; however, the tumor was small and located in the peripheral lung. Many details of this tumor remain unclear, as CMPT is a rare tumor with few reports. CMPT has therefore not yet been classified by the WHO. In this report, we will consider the characteristics of CMPT and treatment based on our case and previous case reports.

Erlotinib and bevacizumab combination therapy for afatinib-refractory leptomeningeal carcinomatosis from EGFR-mutated lung cancer.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors remains the main hurdle in treating EGFR-mutated lung cancer. Besides, when leptomeningeal carcinomatosis occurs during treatment, it often leads to treatment failure. We herein report a case of lung adenocarcinoma involving a patient with an EGFR exon 19 deletion mutation who developed leptomeningeal carcinomatosis after afatinib treatment for post-operative recurrence. He received right lower lobectomy, followed by four cycles of cisplatin and pemetrexed treatment. Follow-up CT/MRI revealed multiple pulmonary metastases and brain metastases at 7 months after surgery, and afatinib (40 mg/day) was administered after stereotactic radiotherapy for brain metastasis. At 28 months after surgery, follow-up MRI revealed asymptomatic leptomeningeal carcinomatosis, which was cytologically proven from the cerebrospinal fluid. Because EGFR T790M was not detected in plasma cell-free DNA or cerebrospinal fluid, erlotinib and bevacizumab combination treatment was administered. He remained asymptomatic and was radiographically clear of LM at 2 months after treatment. In comparison to other EGFR-TKIs, erlotinib shows penetrance into the cerebrospinal fluid. Furthermore, the addition of bevacizumab might enhance the treatment effect, because it is known to relieve brain edema from metastatic brain tumors by normalizing immature vascularity and improving drug penetrance into the cerebrospinal fluid by reducing interstitial fluid pressure.

Elevated red cell distribution width to platelet count ratio predicts poor prognosis in patients with breast cancer.

Red cell distribution width (RDW) to platelet ratio (RPR) is a prognosticator in acute pancreatitis and myocardial infarction; however, the prognostic values of RDW and RPR in breast cancer have not been studied. This retrospective analysis of 299 breast cancer patients investigated the association between RDW and RPR and clinicopathological characteristics and prognosis, compared to platelet distribution width to platelet count ratio (PDW/P) which is a known independent prognostic factor in patients with breast cancer. We found a significant correlation between RPR, and age and HER2 status. An elevated RPR significantly correlated with age and HER2 status. After a median follow-up duration of 48 months, tumour size, nuclear grade, PDW/P, and RPR were recgnized to be significantly associated with lower disease-free survival rates (tumour size: p < 0.01; nuclear grade, PDW/P, and RPR: p < 0.05) in univariate analysis. Tumour size and RPR were significant prognostic factors for lower disease-free survival rates, with hazard ratios of 4.31 (95% confidence interval: 1.76-10.53) (p < 0.01)] and 2.79 [95% confidence interval: 1.01-87.69) (p < 0.05)], respectively, in a multivariate analysis using the Cox proportional hazards model. This is the first study showing that an elevated RPR could independently predict poor prognosis in patients with breast carcinoma. Thus, RPR could be a novel biomarker for prognostic estimation.

Clinical usefulness of serum levels of soluble fms-like tyrosine kinase 1/placental growth factor ratio to rule out preeclampsia in women with new-onset lupus nephritis during pregnancy.

Measurement of the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio may be clinically useful to discriminate systemic lupus erythematosus (SLE) from preeclampsia. Here, we present a pregnant woman with new-onset SLE with hypertension, with the measurement of the sFlt-1/PlGF ratio during pregnancy. A 31-year-old Japanese nulliparous woman, who had been diagnosed with idiopathic thrombocytopenic purpura at 10 years, had a systolic blood pressure of 120 mmHg and was negative for proteinuria at 12+1 weeks. Since her blood pressure increased to 159/86 mmHg with 3+ proteinuria at 25+4 weeks, preeclampsia was suspected. Deterioration of the kidney function (creatinine: 0.58 mg/dL at 24+6 weeks to 0.83 mg/dL at 33+6 weeks) necessitated cesarean section at 33+6 weeks. After delivery, she still showed increased creatinine and proteinuria. Therefore, she was transferred to a nephrology specialist in a tertiary center and was finally diagnosed with SLE with lupus nephritis class IV-G(A) (diffuse lupus nephritis). The serum levels of sFlt-1 and the sFlt-1/PlGF ratio, which are usually elevated in preeclampsia, were within normal reference ranges at 27+6, 28+1, and 28+6 weeks of gestation, although the serum levels of PlGF were slightly lower than the normal reference range. In conclusion, measurement of the sFlt-1/PlGF ratio may be clinically useful to discriminate lupus nephritis from preeclampsia.