━━ Objectives.Myasthenia gravis occasionally develops after thymectomy, even in asymptomatic patients.This condition is termed post-thymectomy myasthenia gravis.Case.A 70-year-old male underwent thymectomy combined with resection of a tumor in the anterior mediastinum that extended to the superior vena cava.A preoperative needle biopsy and intraoperative frozen section revealed the existence of thymic carcinoma.Although the patient was asymptomatic, the titer of anti-acetylcholine receptor antibodies was elevated.He was discharged on the 14th day after surgery.Twenty days after the operation, the patient complained of breathing difficulties in the supine position.He visited our outpatient clinic and was admitted to the hospital for a further detailed examination.He suddenly suffered cardiopulmonary arrest at midnight on the 22nd day after surgery, and, after resuscitation, was treated with a mechanical ventilator.His symptoms abated following the administration of steroid and immunosuppressive therapy.A detailed examination revealed a diagnosis of post-thymectomy myasthenia gravis.The final pathological diagnosis was revised to WHO-classification type B3 thymoma based on the histological findings of the surgical specimen.Conclusions.Special attention should be paid to the potential for post-thymectomy myasthenia gravis, especially in patients with an elevated preoperative anti-acetylcholine receptor antibody level, even those who are asymptomatic.(JJLC.
Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease.
Adenocarcinoma in situ (AIS), which was defined as having a pathologically non-invasive nature by the new IASLC/ATS/ERS classification, might be included in patients that showed part-solid nodule on thin-section CT. Between 2008 and 2011, 556 c-stage IA lung cancer patients underwent pulmonary resection. The findings obtained by preoperative thin-section CT were reviewed for all patients and categorized as pure ground-glass nodule (GGN), part-solid, or pure-solid based on the findings on thin-section CT, i.e. consolidation/tumour ratio (CTR). Part-solid nodule was defined as a tumour with 0 < CTR < 1.0, which indicated focal nodular opacity containing both solid and GGN components. All patients were evaluated by positron emission tomography (PET) and the maximum standardized uptake value (SUVmax) was recorded. Several clinicopathological features were investigated to identify predictors of AIS using multivariate analyses. 112 c-stage IA lung cancer patients showed a part-solid appearance on thin-section CT. Among them, AIS was found in 10 (23.8%) of 42 patients with 0 < CTR ≤ 0.5 in contrast to 3 (4.3%) of 70 patients with 0.5 < CTR < 1.0. According to multivariate analyses, SUVmax and CTR were significant predictors of AIS in patients with part-solid nodule (P = 0.0421, 0.0221). Mean SUVmax of the patients with AIS was 0.57 (0-1.6). Moreover, in the subgroup of part-solid nodule with SUVmax ≤ 1.0 and CTR ≤ 0.40, which were shown as cutoff values of predicting AIS based on the result of receiver operating characteristics curve, 6 (40%) of 15 patients with these criteria showed pathologic non-invasive nature even in the patients with part-solid nodule. Among clinical stage IA adenocarcinoma with part-solid nodule on thin-section CT scan, extremely low level of SUVmax could correspond to a radiologically pure GGO and pathologically AIS. Preoperative tumour SUVmax on PET could yield important information for predicting the non-invasiveness in patients with part-solid nodule. All authors have declared no conflicts of interest.
Abstract The development of tyrosine kinase inhibitors (TKIs) has improved the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The current research priority is to provide viable treatments for patients who have drug-resistant EGFR mutations. We evaluated the drug sensitivity of various EGFR mutants to monotherapies and combination therapies of EGFR-TKIs. In vitro, the transforming potential and drug sensitivity of 357 EGFR variants were assessed. In vivo, we tested the sensitivity of EGFR variants to different regimens of EGFR-TKIs by examining changes in the proportion of each variant within the tumor. Out of 357 variants thoroughly examined for transforming activities, 144 (40.3%) and 282 (79.0%) transformed 3T3 and Ba/F3 cells, respectively. Among the latter variants, 50 (17.7%) were found to be resistant or only partly resistant to osimertinib or afatinib. Four of 25 afatinib-resistant variants (16%) were sensitive to osimertinib, whereas 25 of 46 osimertinib-resistant variants (54.3%) were sensitive to afatinib. Despite the lack of a synergistic impact, TKI combination treatment effectively reduced in vivo the heterogeneous tumors composed of 3T3 cells with different EGFR variants. Regimens starting with afatinib and subsequently switched to osimertinib suppressed tumor development more efficiently than the opposite combination. Combination EGFR-TKI treatment may decrease tumor growth and prevent the development of resistant variants. This work created an experimental model of a heterogeneous tumor to find the best combination therapy regimen and proposes a basic notion of EGFR-TKI combination therapy to enhance the prognosis of NSCLC patients.
We aimed to compare the outcomes of segmentectomy with those of lobectomy in clinical-stage IA radiological solid-predominant non-small-cell lung cancer (NSCLC) >2 cm in maximum tumour size.A retrospective review was performed for radiological solid-predominant NSCLC >2-3 cm in maximum tumour size with a ground-glass opacity component on thin-section computed tomography. Multivariable or propensity score-matched analyses were performed to control for confounders for survival. Overall survival (OS) was analysed using a Kaplan-Meier estimation.Of the 215 eligible cases, segmentectomy and lobectomy were performed in 46 and 169 patients. Multivariable analysis revealed that standardized uptake value (hazard ratio: 1.148, 95% confidence interval: 1.032-1.276, P = 0.011) was an independently significant prognosticators of OS, while the operative mode was not associated (hazard ratio: 0.635, 95% confidence interval: 0.132-3.049, P = 0.570). The 5 y-OS was excellent and did not differ significantly between segmentectomy and lobectomy (95.5% vs 90.2%; P = 0.697), which was also shown in the propensity score analysis (96.8% vs 94.0%; P = 0.406), with a median follow-up time of 5.2 years. Locoregional recurrence was found in 2 (4.3%) segmentectomy and 13 (7.7%) lobectomy (P = 0.443). In the subgroup analysis stratified by solid component size, the 5 y-OS was similar between segmentectomy and lobectomy in the c-T1b and c-T1c groups, respectively [c-T1b (n = 163): 94.1% vs 91.8%; P = 0.887 and c-T1c (n = 52): 100% vs 84.9%; P = 0.197].Segmentectomy showed similar oncological results compared to lobectomy in solid-predominant NSCLC with a ground-glass opacity component >2-3 cm in maximum tumour size. More prospective randomized trials are needed to adequately expand the indication of anatomic segmentectomy for early-stage NSCLC.
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