Clinicopathological predictors of postoperative long-term myasthenic status in resected thymoma with myasthenia gravis.

PURPOSE: Surgical patients with thymoma and myasthenia gravis (MG) must have their MG status and oncological outcomes critically monitored. We aimed to identify clinicopathological predictors of the postoperative MG status. METHODS: We conducted a retrospective review of 40 consecutive surgical patients with MG-related thymomas between 2002 and 2020. The quantitative myasthenia gravis score (QMGS) and Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS) were used to evaluate postoperative MG status. RESULTS: All patients underwent extended total thymectomy. The most common WHO type was type B2 (32%), while 65% of patients had type B1-B3 and 35% had type A-AB thymomas. Eleven patients (28%) achieved controlled MG status in MGFA-PIS 6 months after surgery. This controlled status was observed more frequently in type A-AB than in B1-B3 (57% vs. 12%, p = 0.007). In a multivariate analysis, WHO type (A-AB or B1-B3) was an independent predictor of worsening episodes of MG based on the QMGS (Type B1-B3, hazard ratio: 3.23, 95% confidence interval: 1.12-9.25). At the last follow-up, 23 patients (58%) achieved controlled MG status. The 5-year overall survival rate of all patients was 93.7%. CONCLUSION: The WHO type of thymoma is an informative predictor of postoperative MG status in patients with MG-related thymoma.

Nuss procedure for the treatment of pectus excavatum with dyspnea following oropharyngeal cancer surgery: a case report.

Pectus excavatum (PE) causes cardiopulmonary dysfunction depending on the degree and form of the depression. The patient was a 74-year-old woman with a history of PE. Fourteen years ago, a total glossolaryngectomy was performed for oropharyngeal cancer. Two years later, the patient gradually experienced difficulty in breathing. Computed tomography (CT) revealed severe PE and right main bronchial stenosis. We performed a Nuss procedure for PE repair to surgically release the stenosis of the right main bronchus. Postoperative chest CT showed improvement in the sternal depression and right main bronchial stenosis. Furthermore, shortness of breath was relieved postoperatively. Oropharyngeal cancer surgery may cause tracheal support disruption, leading to leftward shift and severe stenosis of the right main bronchus due to sternum depression. This is an important report regarding respiratory distress caused by a combination of PE and post-oropharyngeal cancer surgery.

Combined Ravitch and Nuss procedure for pectus excavatum with dyspnea following scoliosis repair.

Pectus excavatum (PE) is often associated with scoliosis and can elicit cardiovascular disturbances under rare conditions. Here we report a patient who was treated with a combined Ravitch and Nuss procedure for PE with dyspnea following scoliosis repair to improve her symptoms. The patient was a 49-year-old woman with a history of PE and scoliosis. Right inferior pulmonary vein stenosis was caused by posterior spinal fusion for scoliosis prior to the PE repair. We could safely correct the chest wall deformity and treat dyspnea by performing a modified Ravitch repair in combination with the Nuss procedure.

Combined Ravitch and Nuss procedure for patients with severe pectus excavatum: technique and initial results.

The Nuss procedure for pectus excavatum (PE) is both less invasive and very simple compared to the Ravitch procedure. However, it may be difficult to perform the Nuss procedure in cases of severe PE. Therefore, we developed a Combined Ravitch and Nuss (CRN) procedure and examined its effectiveness in patients with severe PE. Nine patients with severe PE underwent the CRN procedure. Data on patient characteristics and perioperative results were collected retrospectively. The median Haller index (HI) was 15.4 (range, 6.3-29.3). No significant intraoperative adverse events were noted. Postoperatively, marked improvements in HI were seen in all cases (3.29, range, 2.72-4.96). Two surgical site infections on the shallow layer and one wound seroma occurred. No recurrences were observed during the observation period. Our novel CRN procedure is useful for achieving adequate and sustainable sternal elevation with less invasiveness for patients with severe PE.

Prognostic factors affecting survival in patients with non-small cell lung cancer treated with salvage surgery after drug therapy: a multi-institutional retrospective study.

BACKGROUND: The prevalence of salvage surgeries after drug therapy for non-small cell lung cancer (NSCLC) has risen, mainly due to recent progress in molecular-targeted drugs and immune checkpoint inhibitors for NSCLC. While the safety and effectiveness of salvage surgery after drug therapy for NSCLC have been studied, its indications remain unclear. We aimed to identify the prognostic factors affecting survival in patients with advanced-stage (stages III-IV) NSCLC treated with salvage surgery after drug therapy. METHODS: A retrospective investigation was conducted on patients who received salvage surgery after drug therapy at four hospitals between 2007 and 2020. Salvage surgery was defined as surgery after drug therapy for local progression, tumor conversion to resectable status, and discontinuation of prior drug therapy owing to serious complications. RESULTS: Thirty-two patients received cytotoxic agents alone (n = 12 [38%]), tyrosine kinase inhibitors (TKIs; n = 16 [50%]), or immune checkpoint inhibitors (n = 4 [13%]) as prior drug therapy. In 11 (34%) and 21 (66%) patients, the clinical stage before treatment was III or IV, respectively. The median initial and preoperative serum carcinoembryonic antigen (CEA) levels were 10.2 (range, 0.5-1024) ng/mL and 4.2 (range, 0.6-92.5) ng/mL, respectively. Among the patients, 28 (88%) underwent lobectomy, 2 (6%) underwent segmentectomy, and 2 (6%) underwent wedge resection. Complete resection of the primary lesion was accomplished in 28 (88%) patients. Postoperative complications were documented in six (19%) patients. Mortality rates were 0% at 30 days and 3% at 90 days post-operation. The 5-year overall survival rate stood at 66%, while the 5-year progression-free survival rate was 21%. Multivariate analyses showed that prior TKI therapy and preoperative serum CEA level < 5 ng/mL were prognostic factors influencing overall survival (hazard ratio [95% confidence interval]: 0.06 [0.006-0.68] and 0.03 [0.002-0.41], respectively). The 5-year overall survival in the 11 patients with both favorable prognosticators was 100%. CONCLUSIONS: In this study, prior TKI therapy and preoperative serum CEA level < 5 ng/mL were favorable prognostic factors for overall survival in patients with NSCLC treated with salvage surgery. Patients with these prognostic factors are considered good candidates for salvage surgery after drug therapy.

[Clinicopathological Features and Imaging Characteristics of Pulmonary Mucosa-associated Lymphoid Tissue Lymphoma].

BACKGROUND: Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease. We report seven cases of pulmonary MALT lymphoma. CASES: Chest computed tomography (CT) revealed various morphological features, including a solitary mass, a solid nodule, and ground-glass opacity. Multiple nodules were observed in one patient. However, the tumor margins were ill-defined in all seven cases, and air bronchograms were identified in five cases. The solitary mass was found to extend along the pulmonary lymphatic vessels. Six patients underwent R0 resection, while one underwent an open lung biopsy. Histopathological findings in all seven cases showed lymphoepithelial lesions. Regarding their immunohistological findings, all patients were diagnosed with pulmonary MALT lymphoma. Two patients received postoperative chemotherapy with rituximab. The progression-free survival time was 52 (range, 22-122) months. Postoperative course was uneventful in all patients. CONCLUSION: MALT lymphoma is characterized by an ill-defined margin, air bronchogram, and tumor extension along the pulmonary lymphatic vessels, all of which aid in diagnosis. MALT lymphoma is a low-grade lymphoma, and the prognosis is favorable. Therefore, follow-up examination without treatment can be one of the therapeutic options if patients are diagnosed with pulmonary MALT lymphoma.

Feasibility and safety of percutaneous cryoablation under local anesthesia for the treatment of malignant lung tumors: a retrospective cohort study.

Background: In our institution, computed tomography (CT)-guided percutaneous cryoablation has been performed in patients with malignant lung tumors under local anesthesia. This study aimed to examine the feasibility and safety of percutaneous cryoablation for the treatment of malignant lung tumors. Methods: From July 2002 to December 2016, 227 patients (56 with primary lung cancer and 171 with metastatic lung tumor) underwent percutaneous cryoablation for the treatment of malignant lung tumors using a cryosurgical unit at our institution. Demographic factors, duration of post-treatment hospitalization, and adverse event and mortality rates were retrospectively investigated in 366 treatment sessions targeting 609 lesions. Results: The median diameter of the targeted tumor was 1.3 cm. All the cryoablation procedures were completed under local anesthesia, and the median duration of post-treatment hospitalization was two days. Adverse events (grade 2 or higher) were observed in 79 sessions (21.6%), with pneumothorax being the most common. In five sessions (1.4%), patients had grade 3 adverse events. There was no 30-day mortality; however, there were two 60-day mortality (0.5%) due to acute exacerbation of interstitial pneumonia. In multivariate analysis, independent predictors of adverse events were comorbid interstitial pneumonia [odds ratio (OR) =2.20; 95% confidence interval (CI): 1.04-4.64] and no history of pulmonary resection on the treated side (OR =3.04; 95% CI: 1.65-5.62). Conclusions: Cryoablation is a feasible and safe treatment for malignant lung tumors with acceptable adverse event rates. However, the mortality risk in patients with comorbid interstitial pneumonia should be fully recognized.

Double stapling method for closure of intraoperative alveolar air leakage adjacent to the staple line: a randomized experimental study on ex vivo porcine lungs.

Background: Alveolar air leakage from a pleural defect around the staple line is one of the complications after wedge resection of the lung. An intraoperative closure of the pleural defect by suturing can cause additional pleural rupture due to tension of the pleura adjacent to staple lines. Therefore, we have introduced a novel closure method for pleural defect adjacent to the staple line, named the double stapling method. This study compared the efficacy of two closure methods; the double stapling method and conventional suturing method with pledgets using ex vivo porcine lungs. Methods: The double stapling method involves closing the pleural defect by suturing the two parallel staple lines at both sides of the pleural defect. This method was developed to distribute the pleural tension around the needle holes of suturing. As a model of pleural defect adjacent to the staple line after wedge resection, wedge resection of the caudal lobe of left porcine lungs was performed, and a superficial square pleural defect (10 mm × 10 mm) adjacent to the staple line was made by scalpel. The defect was closed using the following two methods: (I) suturing with pledgets (n=10); and (II) double stapling method (n=10). The lobe was inflated in water at an airway pressure of 20, 25, and 30 cmH2O; closure success or failure was judged by the absence or presence of air leakage. Results: The closure success was confirmed in 2 (20%) out of 10 cases in the suturing with pledgets group and 9 (90%) out of 10 in the double stapling method group (P=0.007). In 4 out of 10 cases in the suturing with pledgets group, new pleural clefts longer than 3 mm were created around the needle holes of suturing. Conclusions: Ex vivo experiments have suggested the superiority of the double stapling method for the intraoperative closure of alveolar air leakage adjacent to the staple line after wedge resection, compared to conventional suturing with the pledget method.

Separate evaluation of unilateral lung function using upright/supine CT in a patient with diaphragmatic paralysis.

Background: Unilateral diaphragmatic paralysis is a condition in which the unilateral diaphragm is paralyzed and elevated. Orthopnea due to lung compression by an elevated diaphragm in the supine position is common in patients with unilateral diaphragmatic paralysis. Although its symptom is posture-dependent, the effect of posture on lung function in unilateral diaphragmatic paralysis has not been studied. Computed tomography (CT) can be used to assess lung volume. However, conventional CT cannot be performed in the upright position. A pulmonary function test can be performed in both upright and supine positions. However, it cannot evaluate the function of each lung separately. Case presentation: We report a case of a 79-year-old man with unilateral diaphragmatic paralysis. He presented with difficulty in inspiration, specifically in the supine position, and underwent both conventional supine CT and newly developed upright CT to assess the effect of posture on the function of each lung. The difference between expiratory and inspiratory lung volumes on CT in the supine position was less than that in the upright position by 46% and 4% on affected and healthy sides, respectively. We previously reported that the difference between expiratory and inspiratory lung volumes on CT correlated with inspiratory capacity on the pulmonary function test. A 46% decline in inspiratory capacity on the affected side in the supine position likely caused orthopnea in this patient. Conclusions: Supine/upright CT is helpful to assess the influence of posture on unilateral lung function in patients with unilateral diaphragmatic paralysis.

A 70-Year-Old Woman With Long-Term Nonresolving Pneumonia.

CASE PRESENTATION: A 70-year-old woman who had received a diagnosis of pneumonia in the right lower lobe was treated with antibiotics at a general practitioner's clinic 9 months earlier. Her pneumonia had improved, but the cough and lung infiltrates persisted for > 6 months, so the patient was referred to our hospital. She had undergone surgery for breast cancer 30 years earlier but had no other medical history. She was not taking any medications and had no history of smoking, including passive smoking.

Safety and efficacy of salvage surgery for non-small cell lung cancer: a retrospective study of 46 patients from four Keio-affiliated hospitals.

OBJECTIVES: Advances in drug therapy and radiotherapy for non-small cell lung cancer resulted in an increased number of salvage surgeries for initially unresectable tumors. This study aimed to evaluate the safety and efficacy of salvage surgery for non-small cell lung cancer. METHODS: We defined salvage surgery as (1) surgery for local recurrence/residual tumor after definitive chemoradiotherapy/radiotherapy (salvage surgery in a narrow sense) or (2) conversion surgery after non-surgical treatment. We retrospectively analyzed patients who underwent salvage surgery at four Keio University-affiliated hospitals. RESULTS: Forty-six patients were included. The initial clinical stage was I in 4 patients (9%), III in 19 (41%), and IV in 23 (48%). Initial treatment before salvage surgery was chemoradiotherapy in 10 patients (24%), radiotherapy in 4 (9%), and drug therapy in 32 (67%). Pneumonectomy, lobectomy, segmentectomy, and wedge resection were performed in 2 (4%), 37 (80%), 3 (7%), and 4 (9%) patients, respectively. Complete resection was achieved in 41 patients (89%). Postoperative complications occurred in 11 patients (24%). Initial chemoradiotherapy/radiotherapy was an independent predictor of postoperative complications (odds ratio 10, p = 0.03). The 30- and 90-day mortality rates were 0 and 2%, respectively. The 5-year overall and progression-free survival rates were 66 and 30%, respectively. CONCLUSION: The safety and efficacy of salvage surgery for non-small cell lung cancer were acceptable. Salvage surgery was a viable treatment option for selected patients with recurrent/residual tumors after non-surgical treatments.

Debulking surgery for malignant tumors: the current status, evidence and future perspectives.

Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy.

Four cases of completion lobectomy for locally relapsed lung cancer after segmentectomy.

BACKGROUND: Although completion lobectomy is the treatment of choice for local recurrence of non-small cell lung cancer after segmentectomy, few cases have been reported. We report four patients who underwent completion lobectomies for staple line recurrence after segmentectomy for stage I non-small cell lung cancer. CASE PRESENTATION: Three women aged 65, 82, and 81 years underwent completion lower lobectomy after superior segmentectomy of the same lobe for local recurrence of stage I non-small cell lung cancer. A 67-year-old man, who had a tumor recurrence on the staple line after apical segmentectomy with superior mediastinal nodal dissection for stage I non-small cell lung cancer, underwent completion right upper lobectomy. These four patients underwent segmentectomy because of comorbidities or advanced age. Local recurrence was confirmed by computed tomography-guided needle biopsy. The interval between the two operations was 37, 39, 41, and 16 months, respectively. Although minimal hilar adhesion was seen for the three completion lower lobectomies, tight adhesions after apical segmentectomy made completion right upper lobectomy quite difficult to dissect, which led to injury of the superior pulmonary vein. No recurrence was recorded after completion lobectomies for 62, 70, 67, and 72 months, respectively. CONCLUSIONS: Although completion lobectomy is one of the most difficult modes of resection, among several completion lobectomies, completion lower lobectomy after superior segmentectomy without superior mediastinal nodal dissection was relatively easy to perform because of fewer hilar adhesions.

Clinicopathological and prognostic features of operable non-small cell lung cancer patients with diabetes mellitus.

BACKGROUND: The aim of this study was to investigate the clinicopathological and prognostic features of operable non-small cell lung cancer (NSCLC) patients with diabetes mellitus (DM). METHODS: A total of 1231 surgically resected NSCLC patients were retrospectively reviewed. Clinicopathological characteristics were compared between patients with DM (DM group, n = 139) and those without DM (non-DM group, n = 1092). The clinical factors associated with postoperative complications and prognostic factors were identified. RESULTS: The DM group had distinct clinicopathological features. No significant differences in histological invasiveness or stage were found. The presence and control status of DM were independent predictors of postoperative complications. No significant differences in recurrence-free survival or cancer-specific survival were observed; however, the DM group had worse overall survival (OS). The DM group had a higher number of deaths from other diseases than the non-DM group, and these patients had significantly higher postoperative hemoglobin A1c levels than patients with cancer-related death. CONCLUSION: The presence and control status of preoperative DM are useful predictors of both postoperative complications and OS in operable NSCLC patients. Concomitant diabetes-related complications have a negative effect on long-term survival in diabetic NSCLC patients, and long-term glycemic control is important to prolong OS.

[Role of Surgery in Multimodality Treatment for Non-small Cell Lung Cancer;Current Status and Future Perspectives].

Recent improvement of outcomes for resected non-small cell lung cancer (NSCLC) has been contributed not only by increased detection of early-stage disease and improvement of preoperative diagnosis/perioperative management but also by improvement of multimodality treatment. The introduction of newly developed systemic therapies including molecular targeted agents and immune checkpoint inhibitors dramatically changed clinical outcomes of advanced NSCLC. Accordingly, the role of surgery during the multimodality treatment will be changed more than ever. In this article, we overviewed the current status of the multimodality treatment for clinical stageⅢ (N2)disease and postoperative adjuvant therapy and discussed the role of surgery during these situations. We also discussed the future perspectives of the role of surgery during the multimodality treatment for advanced NSCLC.

Clinical Features of Ground Glass Opacity-Dominant Lung Cancer Exceeding 3.0 cm in the Whole Tumor Size.

BACKGROUND: Ground glass opacity (GGO)-dominant lung adenocarcinoma sized 3.0 cm or less in the whole tumor size is widely known to have an excellent prognosis and is regarded as early lung cancer. However, the characteristics and prognosis of lung cancer showing GGO exceeding 3.0 cm remains unclear. METHODS: From 2002 through 2012, we reviewed 3,735 lung cancers that underwent complete resection at our institution. We identified 160 lung cancers (4.3%) showing GGO exceeding 3.0 cm on thin-section computed tomography and divided them into three types by the consolidation/tumor ratio (CTR) using cutoff values of 0.25 and 0.5. We compared the characteristics and prognosis among these types. RESULTS: Type A (CTR, 0 to ≤0.25), type B (CTR, >0.25 to ≤0.5), and type C (CTR, >0.5 to <1.0) were found in 16 (10%), 37 (23%), and 107 lesions (67%), respectively. No lymph node metastasis was found in types A and B. Recurrence was not observed in types A and B. The 5-year overall survival and disease-free survival rates were both 100% in type A, both 97.2% in type B, and 88.4% and 66.7% in type C, respectively. Patients with type C had a significantly worse prognosis than those with the other types with respect to overall survival and disease-free survival. CONCLUSIONS: A patient with GGO-dominant lung cancer exceeding 3.0 cm can be considered to be in a group of patients with nodal-negative disease and an excellent prognosis.

Deleterious Pulmonary Surfactant System Gene Mutations in Lung Adenocarcinomas Associated With Usual Interstitial Pneumonia.

PURPOSE: Usual interstitial pneumonia (UIP) is a risk factor for lung carcinogenesis. This study was performed to characterize mutagenesis and mutational target genes underlying lung carcinogenesis in patients with UIP. PATIENTS AND METHODS: A cohort of 691 Japanese patients with lung adenocarcinoma (LADC), of whom 54 had UIP and 637 did not, was studied for driver oncogene aberrations. Whole-exome analysis was performed for 296 cases, including 51 with UIP, to deduce mutagenic processes and identify commonly affected genes. Logistic regression analysis was used to detect associations of gene aberrations with clinicopathological factors. RESULTS: The EGFR mutation was markedly less prevalent in patients with LADC with UIP than in those without (1.9% [one of 54] v. 49.9% [318 of 637]; P < .001), even in heavy smokers (25.3% [38 of 150] of patients with > 40 pack-years; P < .001). Mutational signature analysis indicated that UIP-positive LADCs develop through accumulation of single-nucleotide and indel mutations caused by smoking. Pulmonary surfactant system genes (PSSGs) NKX2-1/TTF1, SFTPA1, SFTPA2, SFTPB, and SFTPC were identified as targets for mutations (preferentially indels), and mutations were specifically associated with shorter overall survival of patients with UIP-positive LADC, independent of pathologic stage (hazard ratio, 4.9; 95% CI, 1.7 to 14.4; P = .0037). CONCLUSION: LADCs with UIP develop through mutational events caused by smoking, independently of EGFR mutation. PSSGs were identified as a mutational target and as a novel prognostic factor in UIP-positive LADC. PSSG deficiency might increase the malignancy of tumor cells by increasing the tumor-promoting effects of UIP.

Prognostic Impact of Margin Distance and Tumor Spread Through Air Spaces in Limited Resection for Primary Lung Cancer.

OBJECTIVES: The aim of this study was to investigate the relationship between clinicopathological prognostic factors, including surgical margin distance and tumor spread through air spaces (STAS), and recurrence after limited resection for primary lung cancer. METHODS: We identified 508 cases of limited resection (12.8%) and examined their clinicopathological features. Using Cox regression analysis, we examined the significant prognostic factors for recurrence of limited resection. Finally, we conducted a histopathological evaluation of tumor STAS. RESULTS: Multivariate Cox analysis showed that the risk for local recurrence was significantly associated with STAS (hazard ratio = 12.24, p = 0.001) and a tumor margin less than 1.0 cm (hazard ratio = 6.36, p = 0.02). However, the presence of tumor STAS was not significantly associated with distant recurrence (p = 0.98). This lack of association of STAS with distant recurrence may be due to the small number of distant recurrences. In all, 76 cases (15.0%) (60 adenocarcinomas, nine squamous cell carcinomas, and seven others) were positive for STAS. The morphological STAS patterns were 12 single cells, 45 small cell clusters, and 19 large nests. There was no significant relationship between the recurrence rate and morphological STAS pattern. The STAS-positive group was associated with the presence of micropapillary (p = 0.002) and/or solid components (p = 0.008) in patients with adenocarcinoma and with lymphovascular and pleural invasion (p < 0.001). CONCLUSIONS: The presence of STAS and tumor margins less than 1.0 cm are significant risk factors for local recurrence in early-stage lung cancer after limited resection. Thus, the presence of tumor STAS might be a pathological prognostic factor for patients with lung cancer who have undergone limited resection. However, the pathological and molecular significance of STAS remain to be clarified.