Impact of central nervous system metastasis after complete resection of lung adenocarcinomas harboring common EGFR mutation - A real-world database study in Japan: The CReGYT-01 EGFR study.

OBJECTIVES: To clarify the impact of central nervous system (CNS) metastasis on performance status (PS) at relapse, on subsequent treatment(s), and on survival of patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutation. METHODS: We conducted the multicenter real-world database study for patients with radical resections for lung adenocarcinomas between 2015 and 2018 at 21 centers in Japan. EGFR mutational status was examined at each center. RESULTS: Of 4181 patients enrolled, 1431 underwent complete anatomical resection for lung adenocarcinoma harboring common EGFR mutations. Three-hundred-and-twenty patients experienced disease relapse, and 78 (24%) had CNS metastasis. CNS metastasis was significantly more frequent in patients with conventional adjuvant chemotherapy than those without (30% vs. 20%, P = 0.036). Adjuvant chemotherapy did not significantly improve relapse-free survival at any pathological stage (adjusted hazard ratio for stage IA2-3, IB, and II-III was 1.363, 1.287, and 1.004, respectively). CNS metastasis did not affect PS at relapse. Subsequent treatment, mainly consisting of EGFR-tyrosine kinase inhibitors (TKIs), could be equally given in patients with or without CNS metastasis (96% vs. 94%). Overall survival after relapse was equivalent between patients with and without CNS metastasis. CONCLUSION: The efficacy of conventional adjuvant chemotherapy may be limited in patients with lung adenocarcinoma harboring EGFR mutations. CNS metastasis is likely to be found in practice before deterioration in PS, and may have little negative impact on compliance with subsequent EGFR-TKIs and survival after relapse. In this era of adjuvant TKI therapy, further prospective observational studies are desirable to elucidate the optimal management of CNS metastasis.

Clinicopathologic and Genotypic Features of Lung Adenocarcinoma Characterized by the International Association for the Study of Lung Cancer Grading System.

INTRODUCTION: The new grading system proposed by the Pathology Committee of the International Association for the Study of Lung Cancer in 2020 was based on the combination of the histologically predominant subtype and high-grade component. Because the predominant subtypes are associated with characteristic subsets, unique subsets can be identified by this grading system. METHODS: We analyzed the clinicopathologic, genotypic, and prognostic features of a cohort of 781 consecutive patients with invasive nonmucinous adenocarcinoma of the lung. RESULTS: Grade 3 tumors were associated with younger age, male sex, a higher smoking dose, and aggressive features (tumor size, lymph node metastasis, stage, lymphovascular invasion, and pleural invasion). Recurrence-free survival and 3-year overall survival were well-stratified according to tumor grade, and the differences were confirmed with multivariate analysis using the Cox proportional hazard model. Radiologically, most grade 3 tumors exhibit a solid nodular pattern on computed tomography images and a high maximum standardized uptake value with positron emission tomography. Genotypically, 43% of the grade 3 adenocarcinomas lacked any driver mutations, although one of the driver mutations was detected in 79% of grade 1 or 2 tumors. Patient age, positive smoking history, solid nodule on computed tomography image, and higher maximum standardized uptake value were identified as significant preoperative predictive factors of grade 3 tumors, with a prediction rate greater than 90%. CONCLUSIONS: Besides stratifying the patient outcomes, the new grading system characterized unique clinicopathologic subsets and this study suggested that grade 3 tumors could be predicted using the preoperative variables.

Treatment of anemia associated with chronic kidney disease with the HIF prolyl hydroxylase inhibitor enarodustat: A review of the evidence.

Enarodustat, a newly developed hypoxia-inducible factor prolyl hydroxylase inhibitor, is used in clinical practice in Japan. Several clinical studies showed that enarodustat corrected and maintained hemoglobin (Hb) levels by stimulating endogenous erythropoietin production and improving iron utilization in anemic patients with chronic kidney disease, regardless of whether they were on dialysis. In addition, Phase III comparative studies demonstrated that enarodustat was noninferior to darbepoetin alfa in controlling Hb levels. Furthermore, enarodustat was well tolerated during the treatment. Enarodustat is currently being developed in the Republic of Korea and China and is expected to be developed worldwide. This article reviews the data on enarodustat, including the findings from preclinical studies, pharmacokinetics/pharmacodynamics, and efficacy and safety results of clinical studies.

Preoperative marking of a submillimeter metastatic pulmonary tumor using a mobile computed tomography scan with a navigation system: A case report.

INTRODUCTION AND IMPORTANCE: Preoperative localization of non-palpable lung nodules plays an important role in video assisted thoracic surgery (VATS). Although percutaneous computed tomography (CT)-guided hook wire marking has become widely accepted, it is accompanied by rare but fatal complications such as air embolisms. We herein report a case of a submillimeter pulmonary nodule successfully localized by a mobile CT scan with a navigation system. CASE PRESENTATION: A 40-year-old-man presented with the two right pulmonary nodules 4 years after a radical left nephrectomy for a renal clear cell carcinoma. One of the nodules was too small to palpate and preoperative marking was applied using a mobile CT scan with a navigation system. We successfully performed VATS wedge resection for both nodules and confirmed a pathological diagnosis of a metastasis from the renal cell carcinoma. The maximum pathological size of the smaller nodule was 500 µm. CLINICAL DISCUSSION: Preoperative marking of the lower lobe lesion in the present case was essential for VATS. Our novel technique was helpful for the precise marking without any morbidity. CONCLUSION: Preoperative marking using a mobile CT scan with a navigation system is safe and easily applicable. It might be a useful option for VATS of non-palpable lung nodules.

Narrow band imaging for thoracic endometriosis.

BACKGROUND: The thoracic cavity is the most frequent site of extrapelvic endometriosis. It exhibits a wide variety of clinical manifestations, such as chest pain, cough, and respiratory distress, and is frequently associated with pelvic endometriosis. Although histological confirmation is the gold standard for a definitive diagnosis, endoscopic identification of the affected area is often difficult. Narrow band imaging (NBI) is an imaging technique that emphasizes vascular structures and is reported to be useful in the diagnosis of pelvic endometriosis. CASE PRESENTATIONS: A 31-year-old woman and 39-year-old woman developed a recurrent right pneumothorax during their menstruation cycles. They both had no medical history suggesting pelvic endometriosis. We planned an elective video-assisted thoracoscopic surgery for the suspicion of thoracic endometriosis. In addition to white light alone, an NBI observation enhanced the microvasculature of the suspected lesions and allowed us to identify the affected area more clearly. Partial resections of the diaphragm were performed. Histopathological and immunohistochemical studies of each specimen confirmed the diagnosis of extrapelvic endometriosis. CONCLUSIONS: NBI may improve the diagnostic accuracy for thoracic endometriosis, especially in clinically suspected patients but without a history of pelvic endometriosis.

Nontraumatic warfarin-related intrapulmonary hemorrhage presenting as a lung mass.

BACKGROUND: Although bleeding events are the major concern when using oral anticoagulants, intrathoracic hemorrhages due to warfarin are rare. Most cases in the literature have been related to trauma and have manifested as a hemothorax. Here we report a case of a nontraumatic hemorrhage within a pre-existing pulmonary cyst that presented as a lung mass during warfarin therapy. CASE PRESENTATION: A 75-year-old asymptomatic woman presented with a 10-cm-diameter mass on chest radiography that was not evident 6 months prior. She had been taking warfarin for paroxysmal atrial fibrillation and a transient ischemic attack. There was no history of chest trauma, warfarin overdosing, or any suspected interactions with other drugs such as nonsteroidal anti-inflammatory drugs or antibiotics. The prothrombin time/international normalized ratio(PT-INR) was prolonged at 4.73 and her hemoglobin level was 8.7 g/dl. Chest computed tomography(CT)revealed an air-fluid mass adjacent to the right upper and middle lobes with a pleural effusion. A CT scan obtained 15 years prior revealed a cyst at the corresponding site and the mass was diagnosed as a warfarin-related hemorrhage within the pre-existing pulmonary cyst. We performed a surgical resection of the cyst to prevent any worsening hemorrhage and subsequent infection. The postoperative course was uneventful and the patient was discharged on the 3rd postoperative day. CONCLUSION: A warfarin-related thoracic hemorrhage, other than a hemothorax, could manifest as a pulmonary mass on radiography in patients with pre-existing pulmonary cysts. History taking especially of any anticoagulant medications and a precise assessment of the past images are crucial for a correct diagnosis. Once the intrapulmonary cystic hemorrhage becomes evident, prompt withdrawal with a reversal of warfarin and surgical resection are required to prevent a worsening hemorrhage and subsequent infection.

Marking method for peripheral non-palpable pulmonary nodules using a mobile computed tomography scanner with a navigation system.

Intraoperative localization is essential for video-assisted thoracoscopic surgery of non-palpable pulmonary nodules. Although a computed tomography (CT) guided hook-wire localization is widely used, it might be accompanied by a rare but fatal complication such as an air embolism. We applied a mobile CT scanner with a navigation system to resolve this problem. The three-dimensional images obtained by the mobile CT scanner were transferred to the navigation system, which allowed for virtual fluoroscopy to scan the nearest skin site from the target lesion using a navigation probe. The lung surface was stamped by a dyed gauze ball anchored just beneath the skin marking and a needle was placed at this point as a landmark. With this method, we could verify the positional relationship between the needle and target lesion by the additional CT scan without any procedure-related morbidity.

A case of a primary pulmonary meningioma mimicking a metastasis from a papillary thyroid carcinoma due to a size reduction after radioactive iodine therapy.

BACKGROUND: Primary pulmonary meningiomas (PPMs) are a rare mostly benign disease presenting as a solitary pulmonary nodule and are hardly distinguishable from a metastatic tumor because of a lack of specific radiological features. We described a case of a PPM initially diagnosed as a metastatic lung tumor from thyroid cancer with a size reduction after radioactive iodine therapy. CASE PRESENTATION: A 62-year-old woman who had undergone a total thyroidectomy for a papillary thyroid carcinoma 6 years prior presented with an enlarging pulmonary nodule. The nodule had decreased in size from 7.0 to 5.5 mm after adjuvant radioactive iodine therapy and enlarged to 8.7 mm over the next 5 years. Under a clinical diagnosis of a metastatic lung tumor, she underwent a thoracoscopic pulmonary wedge resection and was pathologically diagnosed with a PPM. CONCLUSION: A surgical resection is required for histological diagnoses of PPMs especially in patients with a history of a malignancy.

Delayed bleeding due to a sharp protruding edge of the endostaplers after a wedge resection of the lung: a case report.

BACKGROUND: Endoscopic devices often cause device-related surgical morbidities such as postoperative bleeding. Delayed bleeding due to a protruding edge of an endostapler has not been previously described in the literature. CASE PRESENTATION: An 80-yr-old man with a second primary lung cancer underwent a wedge resection of the right lower lobe. He developed sudden hypotension and massive bleeding from the chest tube 4 h after the surgery and underwent an emergency reoperation. A torn parietal pleura was found to have caused a persistent bleeding. There was a sharp protruding edge created by multiple firings of the endostapler. The subsequent lung expansion would have promoted a direct contact between the edge and parietal pleura resulting in delayed bleeding. CONCLUSIONS: A protruding edge due to multiple firings of an endostapler could injure the parietal pleura and cause delayed bleeding after a lung resection. This type of injury would be more common in wedge resection cases because of the larger residual lung volume preserved, which is expected to have a better lung expansion and facilitate the direct contact of the staple line and parietal pleura.

Primary thymic MALT lymphoma in a patient with Sjögren's syndrome and multiple lung cysts: a case report.

BACKGROUND: Thymic mucosa-associated lymphoid tissue (MALT) lymphoma is rare and also known for its association with autoimmune diseases, especially Sjögren's syndrome (SjS), which could affect the systemic organs, and pulmonary involvement often reveals multiple lung cysts. CASE PRESENTATION: A 40-year-old woman presented with an anterior mediastinal mass and multiple lung cysts on computed tomography. We suspected thymoma concomitant with lymphangioleiomyomatosis and performed a total thymectomy and wedge resection of the lung as a surgical biopsy. The histopathological diagnosis of the mediastinal mass was a MALT lymphoma, and there were no specific findings in the lung specimen. She had a history of SjS, which had been overlooked during the initial work-up. CONCLUSIONS: A history of SjS should raise suspicion of a MALT lymphoma for the differential diagnosis of an anterior mediastinal mass. A precise history taking is crucial for the correct diagnosis, and we could have avoided a lung resection in our case.

Palliative fenestration for a symptomatic subcarinal bronchogenic cyst by the prone position approach.

A complete excision is the most reliable therapy for bronchogenic cysts (BC) but is often accompanied by technical difficulties due to severe adhesions. An 83-year-old-woman with poorly controlled diabetes noted worsening upper abdominal pain after meals and paroxysmal atrial fibrillation. Magnetic resonance imaging revealed a cystic mass in the subcarinal region, and she underwent a thoracoscopic prone position surgery. The cyst wall was found to have strictly adhered to the adjacent organs, and the lesion was not amenable to a complete excision. We performed a fenestration of the cyst wall with the aspiration of an yellowish mucus content. After opening the cavity wide enough, the remnant luminal epithelium was ablated by electrocautery. Her clinical symptoms disappeared immediately after the surgery without any surgical morbidity. A prone-position thoracoscopic palliative fenestration is a feasible option for a symptomatic subcarinal BC.

Prone position surgery for a subcarinal bronchogenic cyst.

BACKGROUND: Prone position surgery has become widespread for esophageal cancer instead of the traditional lateral decubitus approach. Carbon dioxide insufflation and the gravity effect provide a better operative field without parenchymal retraction. We herein report a case of a subcarinal bronchogenic cyst, which was successfully removed by the prone position surgery. CASE PRESENTATION: A 65-year-old man presented with a subcarinal mass and was planned to undergo a surgical resection in the prone position. Although he required bilateral ventilation due to hypoxemia, the excellent operative field was maintained and we completed the thoracoscopic surgery without any additional parenchymal retractions. CONCLUSIONS: Thoracoscopic surgery in the prone position is a feasible option for subcarinal tumors with an excellent operative view and would facilitate a solo surgery without the need for a skilled assistant.

Perovskite-Type InCoO3 with Low-Spin Co3+: Effect of In-O Covalency on Structural Stabilization in Comparison with Rare-Earth Series.

Perovskite rare-earth cobaltites ACoO3 (A = Sc, Y, La-Lu) have been of enduring interest for decades due to their unusual structural and physical properties associated with the spin-state transitions of low-spin Co3+ ions. Herein, we have synthesized a non-rare-earth perovskite cobaltite, InCoO3, at 15 GPa and 1400 °C and investigated its crystal structure and magnetic ground state. Under the same high-pressure and high-temperature conditions, we also prepared a perovskite-type ScCoO3 with an improved cation stoichiometry in comparison to that in a previous study, where synthesis at 6 GPa and 1297 °C yielded a perovskite cobaltite with cation mixing on the A-site, (Sc0.95Co0.05)CoO3. The two perovskite phases have nearly stoichiometric cation compositions, crystallizing in the orthorhombic Pnma space group. In the present investigation, comprehensive studies on newly developed and well-known Pnma ACoO3 perovskites (A = In, Sc, Y, Pr-Lu) show that InCoO3 does not fulfill the general evolution of crystal metrics with A-site cation size, indicating that InCoO3 and rare-earth counterparts have different chemistry for stabilizing the Pnma structures. Detailed structural analyses combined with first-principles calculations reveal that the origin of the anomaly for InCoO3 is ascribed to the A-site cation displacements that accompany octahedral tilts; despite the highly tilted CoO6 network, the In-O covalency makes In3+ ions reluctant to move from their ideal cubic-symmetry position, leading to less orthorhombic distortion than would be expected from electrostatic/ionic size mismatch effects. Magnetic studies demonstrate that InCoO3 and ScCoO3 are diamagnetic with a low-spin state of Co3+ below 300 K, in contrast to the case of (Sc0.95Co0.05)CoO3, where the high-spin Co3+ ions on the A-site generate a large paramagnetic moment. The present work extends the accessible composition range of the low-spin orthocobaltite series and thus should help to establish a more comprehensive understanding of the structure-property relation.