Disseminated Penicillin-Resistant Streptococcus pneumoniae Infection: A Case Report.

An invasive pneumococcal disease involving sternoclavicular joint arthritis, lumbar spondylodiscitis, and muscular abscesses caused by penicillin-resistant Streptococcus pneumoniae has not been reported previously. We successfully treated a 57-year-old man with this condition using surgical drainage and debridement, and laminectomy/fenestration, in combination with the administration of two IV antimicrobial drugs based on blood culture results. Clinical resolution was obtained after decompression of the lumbar spine, with minimal restriction of the left lower limb. This treatment approach should be considered depending on the pathogen, underlying host factors, and the severity of the disease.

Malignant involvement of the iliopsoas muscle associated with non-small cell lung cancer: Two case reports.

Under the current progression of molecular targeting or immune therapy, early detection and radiation therapy of iliopsoas metastasis will not only improve performance status but also enable the continuation of effective systemic cancer treatment.

Anaplastic Lymphoma Kinase (ALK)-Rearranged Lung Cancer That Showed Exclusively Scattered Isolated Cells Devoid of Mucin Production in Cytology.

We present a rare case of Anaplastic Lymphoma Kinase (ALK)-rearranged lung cancer characterized by isolated scattered mucin-free cancer cells forming no clusters in the cytology of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples from a paratracheal lymph node. A female patient in her late 40s underwent chest and abdominal CT scan, revealing a 6 cm diameter tumor in the upper lobe of the left lung along with enlargement of mediastinal and hilar lymph nodes, bilateral pleural effusion, and an additional 5.5 cm diameter tumor in the right greater psoas muscle. EBUS-TBNA was performed to obtain samples for cytological and histological examination. Cytology showed exclusively solitary cancer cells that were negative for Periodic Acid-Schiff (PAS) and Alcian blue staining, without clusters. Immunohistochemical analysis of cell block and histology specimens demonstrated positive expression of TTF-1, ALK, and vimentin, while E-cadherin expression was absent. Genetic analysis of samples obtained by EBUS-TBNA confirmed the presence of EML4-ALK fusion. The tumor in the right greater psoas muscle was identified as a metastatic tumor from the lung tumor based on ALK-positivity and the EML4-ALK fusion. The absence of E-cadherin expression and the presence of vimentin expression suggest that this ALK-rearranged lung cancer may have undergone epithelial-mesenchymal transition, resulting in the loss of cellular adhesiveness.

Efficacy and safety of 5-aminolevulinic acid in adult-onset Still's disease: A preclinical study in mice and a pilot study in humans.

The study aimed to investigate the therapeutic effects of 5-aminolevulinic acid/sodium ferrous citrate (5-ALA/SFC) on adult-onset Still's disease (AOSD), specifically focusing on arthritis and macrophage activation syndrome (MAS). We used mouse models to assess the impact of 5-ALA/SFC on collagen-induced arthritis (CIA) and MAS induced by synthetic oligonucleotides containing CpG motifs (CpG-S-ODN). Additionally, we conducted a pilot study with AOSD patients receiving prednisolone (PSL) treatment and 5-ALA/SFC administration to evaluate its efficacy and safety. The 5-ALA/SFC group exhibited significantly lower joint scores in CIA mice. In CpG-S-ODN-treated mice, 5-ALA/SFC administration led to reduced hemophagocytosis and splenomegaly. The anti-inflammatory properties of 5-ALA/SFC were attributed to the suppression of CCL4 and CXCL10 production in monocytes and the induction of M2 macrophages. AOSD patients treated with 5-ALA/SFC demonstrated successful PSL tapering without adverse events. Collectively, the administration of 5-ALA/SFC showed promising potential in ameliorating arthritis and MAS in AOSD patients.

Outcomes of surgical resection for pulmonary metastasis from pancreatic cancer.

PURPOSE: As the number of long-term survivors of pancreatic cancer is expected to increase thanks to recent advances in multidisciplinary treatment and earlier diagnoses of pancreatic cancer, we are likely to encounter more cases of postoperative pulmonary nodules. We analyzed the clinical course and prognosis of resection of pulmonary metastases from pancreatic cancer to clarify the prognostic implication of pulmonary metastasectomy for pancreatic cancer. METHOD: We retrospectively analyzed 35 patients who underwent resection of lung metastases after pancreatic cancer surgery. Short- and long-term outcomes and factors associated with the prognosis were analyzed. RESULTS: The observation period was 20 (range, 1-101) months, with 3- and 5-year survival rates of 88.3% and 64.5% from pancreatectomy and 44.1% and 28.3% from lung resection, respectively. A univariate analysis revealed that a period from pancreatic cancer resection to pulmonary nodule shadow detection of < 15 months was associated with a significantly lower overall survival from pancreatic resection than a longer period. Conversely, histological type, stage, size of lung metastases, and resection technique were not associated with the overall survival. CONCLUSION: A long-term prognosis may be expected in some cases with a disease-free interval of ≥ 15 months. Our findings suggest that the disease-free interval may influence the prognosis.

Long-term treatment with ALK inhibitors for postoperative recurrence of ALK-rearranged lung cancer.

We encountered a 40-year-old female patient who developed, in chronological order, carcinomatous pleuritis and lymphangitis, multiple lymph node metastases, brain metastases, and intramedullary spinal cord metastases after resection of lung adenocarcinoma followed by adjuvant chemotherapy. Echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) fusion gene, variant 2 was identified in her cancer cells. By changing the ALK inhibitors from the 1st to 3rd generation each time when metastases were identified and incorporating local treatments in a timely fashion, such as metastasectomy or radiation therapy, she has survived for more than 11 years since the start of treatment, while maintaining a good Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0. To our knowledge, this is the first reported case in which ALK fusion variant 2 was identified and prolonged disease control was achieved with the continuous prescription of ALK tyrosine kinase inhibitors (TKIs) and timely consolidative treatments.

The histological diagnosis and molecular testing of lung cancer by surgical biopsy for intrathoracic lesions.

OBJECTIVES: Accurate histological diagnosis and molecular testing using a sufficient tumor sample of advanced lung cancer, especially non-small cell lung cancer (NSCLC), are crucial for precision medicine. The aim of this study was to assess the feasibility and safety of surgical biopsy for intrathoracic lesions, and, in addition, overall survival after surgical biopsy. METHODS: One hundred-one patients who underwent surgical biopsy for intrathoracic lesions of lung cancer at our hospital between 2011 and 2019 were retrospectively reviewed. Their clinical and pathologic records were reviewed. In addition to evaluating the oncologic safety of the surgical biopsy, the overall survival based on the biopsy results was estimated. RESULTS: The total number of surgical sites of the 101 patients was 131, and common biopsy sites were the lungs (82, 62.6%) followed by hilar/mediastinal lymph nodes (27, 20.6%). There were 13 postoperative complications (12.9%) without surgery-related deaths. The median time from surgical biopsy to the initiation of treatment was 27 days. Appropriate amounts of specimens for diagnosis and molecular testing were obtained from all patients (100%). When limited to treatment-naïve patients with stage IV adenocarcinoma, patients treated with tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) based on molecular testing had a better prognosis. CONCLUSIONS: Surgical biopsy for intrathoracic lesions of lung cancer may be a safe and effective method to make a definitive diagnosis, including companion diagnostics for advancing precision therapy in selected patients with inoperable advanced NSCLC.

Analysis of pulmonary nodules caused by nontuberculous mycobacteriosis in 101 resected cases: multi-center retrospective study.

BACKGROUND: Solitary pulmonary nodules caused by nontuberculous mycobacteriosis are included as a category of pulmonary nontuberculous mycobacterium disease. Clinical characteristics, treatments and prognosis are not fully known because there are a few related reports. METHODS: This was a multi-center retrospective study of 101 cases diagnosed as solitary nodular type of nontuberculous mycobacteriosis from January 2000 to March 2017 that underwent resection at 9 related facilities belonging to the Thoracic Surgery Study Group of Osaka. RESULTS: The most common pathogen was Mycobacterium avium complex (n=77, 87.5%), followed by Mycobacterium kansasii (n=8, 9.1%). Chest computed tomography results showed subpleural locations that were difficult to distinguish from lung cancer. Fluorodeoxyglucose positron emission tomography/computed tomography was performed in 58 cases and positive results were obtained in 35 (60.3%), with an average maximum standardized uptake value of 3.87. The purpose of resection in most cases was for diagnosis. The surgical procedure was wedge resection in 87, segmentectomy in 3, and lobectomy in 11, while 77 underwent thoracoscopic surgery. Postoperative complications occurred in 7 cases, though no infections caused by nontuberculous mycobacteriosis were noted. The median observation period was 27 months. A worsened condition occurred in 10 (9.9%) with Mycobacterium avium complex, though none had local recurrence. CONCLUSIONS: Solitary pulmonary nodules due to nontuberculous mycobacteriosis is difficult to diagnose based on preoperative examination results or distinguish from lung cancer. Among the present cases, none had local complications or recurrence, even in those that underwent a wedge resection, thus postoperative chemotherapy was not considered necessary if a complete resection was performed. On the other hand, some cases showed reinfection after a long period following resection, thus patients should be informed of that future possibility.

Heterozygous disruption of ALAS1 in mice causes an accelerated age-dependent reduction in free heme, but not total heme, in skeletal muscle and liver.

5-Aminolevulinic acid (ALA) is the rate-limiting intermediate in heme biosynthesis in vertebrate species; a reaction catalyzed by the mitochondrial ALA synthase 1 (ALAS1) enzyme. Previously we reported that knockdown of the ubiquitously expressed ALAS1 gene in mice disrupts normal glucose metabolism, attenuates mitochondrial function and results in a prediabetic like phenotype when animals pass 20-weeks of age (Saitoh et al., 2018). Contrary to our expectations, the cytosolic and mitochondrial heme content of ALAS1 heterozygous (A1+/-) mice were similar to WT animals. Therefore, we speculated that regulatory "free heme" may be reduced in an age dependent manner in A1+/- mice, but not total heme. Here, we examine free and total heme from the skeletal muscle and liver of WT and A1+/- mice using a modified acetone extraction method and examine the effects of aging on free heme by comparing the amounts at 8-12 weeks and 30-36 weeks of age, in addition to the mRNA abundance of ALAS1. We found an age-dependent reduction in free heme in the skeletal muscle and liver of A1+/- mice, while WT mice showed only a slight decrease in the liver. Total heme levels showed no significant difference between young and aged WT and A1+/- mice. ALAS1 mRNA levels showed an age-dependent reduction similar to that of free heme levels, indicating that ALAS1 mRNA expression levels are a major determinant for free heme levels. The free heme pools in skeletal muscle tissue were almost 2-fold larger than that of liver tissue, suggesting that the heme pool varies across different tissue types. The expression of heme oxygenase 1 (HO-1) mRNA, which is expressed proportionally to the amount of free heme, were similar to those of free heme levels. Taken together, this study demonstrates that the free heme pool differs across tissues, and that an age-dependent reduction in free heme levels is accelerated in mice heterozygous for ALAS1, which could account for the prediabetic phenotype and mitochondrial abnormality observed in these animals.

Outcomes of surgical resection for pulmonary metastasis from ovarian cancer.

BACKGROUND: Due to its rarity, information on pulmonary metastasectomy for pulmonary metastasis from ovarian cancer is limited. METHODS: Cases of pulmonary metastasectomy for ovarian cancer were collected in a multi-institutional setting and the outcomes were analyzed. RESULTS: Among 1508 cases in which pulmonary resection was performed to treat pulmonary metastasis from tumors of various organs, 6 cases (0.4%) involved pulmonary metastasis from ovarian cancer. The mean age was 61 years (range, 39-75 years). The histological types were undifferentiated carcinoma in 2 patients, and clear cell adenocarcinoma, serous papillary cystadenocarcinoma, serous adenocarcinoma, and endometroid adenocarcinoma in 1 patient each. One patient (17%) had a history of liver metastasis at the time of pulmonary resection. The median disease-free interval was 22 months (range, 0 [synchronous]-188 months). The tumor was solitary in 5 patients (83%). The mean tumor size was 15 mm (range, 5-23 mm). All 6 patients underwent complete resection. The type of resection was wide wedge resection in 3 patients, segmentectomy in 2 patients, and lobectomy in 1 patient. Four patients (67%) received postoperative chemotherapy. Thus far, 4 patients (67%) have experienced recurrence after pulmonary resection. In terms of outcomes, 1 patient who had synchronous pulmonary metastasis with the primary tumor died in the early period after pulmonary resection, 1 patient is alive without recurrence after a short follow-up period (5 months), 3 patients have achieved mid- to long-term survival and are alive with disease (38-61 months), and 1 patient achieved long-term (61 months) disease-free survival. CONCLUSIONS: Patients with pulmonary metastasis from ovarian cancer who fulfill the eligibility criteria for pulmonary metastasectomy are rare. Pulmonary metastasectomy for ovarian cancer can provide favorable outcomes in highly selected patients. Patients with synchronous pulmonary metastasis from ovarian cancer are not good candidates for pulmonary metastasectomy.

Long-Term Outcomes of Pulmonary Metastasectomy for Uterine Malignancies: A Multi-institutional Study in the Current Era.

BACKGROUND: Information on pulmonary metastasectomy (PM) for uterine malignancies in the current era is limited. In the present study, we analyzed the clinical course and results of PM for uterine malignancies in the era of modern imaging diagnostics to clarify the role of PM in the current era in a multi-institutional setting. METHODS: Fifty-seven patients who underwent PM for uterine malignancies between 2006 and 2015 were retrospectively reviewed. The short- and long-term outcomes, along with factors associated with the prognosis, were analyzed. Details of the clinical course after PM were described. RESULTS: The mean age of patients was 59.4 years. The primary tumor was located in the uterus corpus in 34 cases (60%) and in the uterus cervix in 23 cases (40%). The median disease-free interval (DFI) was 32 months. Forty patients (70%) received fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography before PM, and complete resection was achieved in 52 patients (91%). Postoperative complications occurred in 4 patients (7%). Of the 52 patients who underwent complete resection of pulmonary metastases, 28 experienced recurrence, and among these, 17 (60%) underwent local therapy, including six repeat PMs. Among the 52 patients who underwent complete resection, the 5-year relapse-free survival rate was 40.7% and the 5-year overall survival (OS) rate was 68.8%. The univariate analysis revealed that a DFI of ≤ 24 months was associated with significantly poorer OS. CONCLUSIONS: PM for uterine malignancies is safe and provides favorable long-term outcomes in selected patients. Patients with a DFI of > 24 months have better OS and are good candidates for PM.

Lung Cancer Surgery for Patients on Hemodialysis: A Decade of Experience at Multicenter Institutions.

BACKGROUND: The clinical outcome of patients undergoing hemodialysis (HD) has not yet been clarified in lung cancer surgery. The aims of this study were to assess the clinical features, outcomes, and main cause of death after lung cancer surgery in patients undergoing HD and to evaluate the risk factors for postoperative complications. METHODS: The study identified 39 patients undergoing HD who had lung cancer surgery in 9 institutions under the Thoracic Surgery Study Group of Osaka University in Japan between 2007 and 2016. Study investigators retrospectively analyzed the surgical outcomes of these patients. RESULTS: Most patients were male and were smokers. Diabetes mellitus was the most common cause of primary renal disease. Lobectomy with systemic lymph node dissection was performed in 16 patients, and an extended operation was performed in 6 patients. Most patients had a diagnosis of pathologic stage IA (69.2%) lung cancer. The overall complication and mortality rates were 30.8% and 7.7%, respectively. Pneumonia was the most frequently observed complication. Extended operation was significantly associated with complications (P = .04). The 5-year overall survival rate was 57.9%, and the most common cause of death was not primary lung cancer but was a disease related to HD. CONCLUSIONS: Lung cancer surgery for patients undergoing HD provides favorable long-term outcomes despite higher postoperative mortality and morbidity rates. Because an extended operation is significantly associated with postoperative complications, thoracic surgeons should carefully select the type of resection on the basis of a balance between therapeutic benefit and invasiveness in these patients.

Surgery to avoid fatal complications and secure radicality after definitive chemoradiotherapy for clinical T4N2M0 stage IIIB non-small cell lung cancer: a case report.

BACKGROUND: Chemoradiotherapy (CRT) is the standard treatment for c-stage IIIB non-small cell lung cancer (NSCLC); however, patients who respond to CRT are at risk of developing fatal complications such as massive hemoptysis or infection. In such cases, surgery is an alternative option. Currently, there are limited reports on surgery for complications arising during definitive CRT for locally advanced NSCLC. We report a case of hemoptysis after definitive CRT for c-T4N2M0 stage IIIB NSCLC that was successfully treated with lower bilobectomy combined with left atrial resection. CASE PRESENTATION: A 72-year-old man with c-T4N2M0 stage IIIB NSCLC with left atrial invasion developed hemoptysis during CRT, which was discontinued to control hemoptysis. Chest computed tomography revealed a regressed and cavitated tumor. Three weeks after discontinuation of CRT, surgery was performed to avoid fatal complications and secure radicality. We performed lower bilobectomy combined with partial left atrial resection, which was performed using an automatic tri-stapler. The bronchial stump was covered with an omental flap. The resected specimen pathologically showed complete response with fistula between the intermediate bronchus and necrotic cavity in the tumor. His postoperative course was uneventful, and the patient was disease free at 10 months after surgery. CONCLUSIONS: We successfully performed surgery after definitive CRT in a patient with c-T4N2M0 stage IIIB NSCLC. Partial left atrial resection was safely performed with an automatic tri-stapler. A complete pathological response to CRT was achieved. In a case with a chance of complete (R0) resection, when the risk of developing fatal complications might outweigh the risk of post-CRT surgery perioperative complications, surgery should be considered as a treatment option.

Real-time spectrum quantification of tumor-related fluorescence during neurosurgery: A preliminary report.

OBJECTIVES: The fluorescent dye, 5-aminolevulinic acid (5-ALA), is currently applied for fluorescence-guided resections of high-grade gliomas. Present limitations of this technique are qualitative and subjective analyses, which show little of the background structures. This paper describes the intraoperative quantitative analysis of fluorescence intensity, hot-spot enhancement by frame averaging, and observation of surrounding structures by using 1000-nm lighting in real time. PATIENTS AND METHODS: A sample of diluted protoporphyrin IX (PpIX) in a bottle and 37 samples from nine patients with brain lesions were involved in this study. In this preliminary study, we determined appropriate conditions for image averaging and filters and selected the most sensitive spectrometer. In addition, we utilized a 1000-nm lighting system to visualize surrounding structures with no interference from PpIX fluorescence. RESULTS: The novel system permitted the real-time quantitative analysis of PpIX fluorescence in operative fields by illuminating structures with 1000-nm-lighting. The real-time quantification provided subjective evaluations for surgical decision-making. We found good correlations between the fluorescence and PpIX contents in brain tissue. Furthermore, 1000-nm lighting visualized the anatomical structures and PpIX fluorescence simultaneously. CONCLUSION: The combination of spectroscopy and a 1000-nm lighting system could enable surgeons to create a spectrogram of targets of interest while observing background structures. The spectrometer that we selected is highly sensitive to PpIX fluorescence and enables us to perform intraoperative real-time tissue mapping. By using a real-time system, we can perform quantitative and objective evaluations to achieve maximal tumor resection.

[A Case of Pulmonary Metastases of Colon Cancer with Submucosal Invasion].

In general, distant metastasis is uncommon in colorectal submucosal(SM)invasion without lymph node metastasis. We experienced an extremely rare case of synchronous pulmonary metastases for colon cancer in SM invasion. A man in his 70s was seen at the hospital for a positive fecal occult blood test. Colonoscopy revealed 3 lesions in the sigmoid colon and endoscopic mucosalresection revealed 2,000 mm SM invasion in all 3 lesions. Computed tomography showed no signs of distant lymph node or liver metastasis but showed small nodules in both lungs. Radical treatment included laparoscopic anterior resection with lymph node dissection. Histological examination showed no residual tumor in the colon and no lymph node metastasis. Two years after surgery, the number of lung nodules gradually increased and we performed partial resection of the left lung, which was diagnosed as pulmonary metastasis from colon cancer by histological examination. Therefore, we resected the opposite-side pulmonary metastases. The patient has exhibited no other signs of recurrence in the 2 years since the last operation.

Fulminant onset of insulin-dependent diabetes with positive anti-GAD antibody titers during treatment with nivolumab in a patient with NSCLC.

Programmed cell death-1 (PD-1) and programmed cell death-ligand-1 (PD-L1) inhibitors have been highlighted in the field of cancer treatment. The interaction between PD-1 and PD-L1 is thought to play an important role in the regulation of the self-immune tolerance mechanism, so blocking these molecules may cause serious immune-related adverse events (IrAE), including fulminant insulin-dependent (type 1) diabetes. Here, we describe a patient with fulminant type 1 diabetes induced by nivolumab, an anti-PD-1 antibody. The patient, a 78-year-old man, was being treated with nivolumab as a third-line treatment for squamous cell carcinoma of the lung. After three cycles, he experienced an abrupt flare-up of the blood glucose within half a day. His blood glucose further increased without clinical symptoms until his hospital visit. Laboratory data showed the complete exhaustion of intrinsic insulin and the elevation of serum antibody titer to glutamic acid decarboxylase (GAD). Although the patient was previously diagnosed with non-insulin-dependent (type 2) diabetes, his disease activity had been well controlled with oral medication and low-dose insulin therapy until just before the flare-up. Because of the laboratory findings and the extremely rapid onset of hyperglycemia, a diagnosis of fulminant, rather than the rapid onset, type 1 diabetes related to nivolumab therapy was strongly suspected. Our case study indicates that fulminant hyperglycemia can occur extremely rapidly. The blood glucose of patients receiving PD-1 antibody therapy should be closely monitored.

Upfront surgery in patients with clinical skip N2 lung cancer based on results of modern radiological examinations.

BACKGROUND: Direct lymphatic drainage from a primary tumor to the right paratracheal or aortic window lymph nodes is often noted in pN2 disease. This multi-institutional retrospective study investigated the outcomes of upfront surgery in patients with clinical skip N2 disease (N2 disease without N1 disease) and a tumor in the right upper lobe or left upper segment based on results of modern radiological examinations, including positron emission tomography (PET). METHODS: We identified 143 patients with cN2 disease who underwent upfront surgery in 12 institutions under the Thoracic Surgery Study Group of Osaka University between January 2006 and December 2013. Among 143 patients, 94 who underwent PET were analyzed. We classified these patients into Group A (n=39; clinical skip N2 disease and a tumor in the right upper lobe or left upper segment) and Group B (n=55; other). RESULTS: The median follow-up was 56.5 months. Among the 94 patients, 50 (53.2%) had skip N2 disease and 65 (69.1%) had a tumor in the right upper lobe or left upper segment. The 5-year overall survival (OS) rates of the 94 patients with cN2 disease was 47.9%. The 5-year OS rates for the cN2pN0/1 (n=22) and cN2pN2 (n=70) groups were 74.9% and 41.2%, respectively (P=0.034). The univariate analysis of OS revealed no significant differences in age, sex, histology, carcinoembryonic antigen (CEA) level, tumor size, PET findings, and number of metastatic lymph nodes when these parameters were dichotomized. A significantly better 5-year OS rate was observed in Group A than in Group B (64.0% vs. 37.0%; P=0.039). The multivariate analysis of OS revealed that Group A was a significantly prognostic factor (P=0.030). CONCLUSIONS: Patients with cN2 disease in Group A had a more favorable prognosis. Upfront surgery may be a treatment option for such selected patients with non-small lung cancer in the specific group.

Concurrent combination of irradiation and immune checkpoint inhibitor for recurrent pleomorphic carcinoma of the lung.

We report the case of a 49-year-old patient who developed brain, sternal, and spine metastases almost simultaneously after the radical resection of a yp-T4N0M0 pulmonary pleomorphic carcinoma of the right upper lobe following induction chemotherapy. The left occipital brain metastasis was surgically removed and followed by radiation therapy. The sternal and vertebral metastases were treated with radiation therapy. Concurrently, the immune checkpoint inhibitor nivolumab was administered. After 12 cycles of nivolumab, the two bone metastases were well-controlled. However, the brain metastasis recurred and was surgically removed again. We were able to investigate the tumor-infiltrating lymphocytes in brain metastases resected before and after radio-immunotherapy. The results revealed the increased number of CD8- and CD68-positive cells after the combined therapy compared with before the therapy. In addition, the high-level expression of program death-ligand 1 was maintained in the brain metastasis.

Surgical resection of advanced non-small cell lung cancer after a response to EGFR-TKI: presentation of two cases and a literature review.

BACKGROUND: The usefulness of residual tumor resection after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment remains unclear. We describe two patients who underwent residual tumor resection after responding to EGFR-TKIs for advanced non-small cell lung cancer (NSCLC) harboring EGFR gene mutations, along with a review of the literature. CASE PRESENTATION: The patient in Case 1 was a 72-year-old female non-smoker who was initially diagnosed with T2aN2M0, stage IIIA adenocarcinoma harboring an EGFR exon 21 L858R mutation. After 8 months of gefitinib therapy, a marked radiologic response was noted, and right upper lobectomy with systemic lymph node dissection was performed. The patient developed brain metastasis despite continuous gefitinib therapy. The patient in Case 2 was a 68-year-old female non-smoker who was initially diagnosed with T3N2M0, stage IIIA adenocarcinoma and an extensive pulmonary thromboembolism. After 3 months of therapy with afatinib and anticoagulants, a marked radiologic response and symptom relief were achieved. We then performed right bilobectomy with systemic lymph node dissection. She developed bone metastasis despite postoperative afatinib therapy. CONCLUSION: The timing and validity of salvage surgery for residual lesions remain unclear when TKIs are offered as first-line therapy to patients with advanced NSCLC. In our two cases, surgery was performed without any complications. Surgical resection of the residual tumor might contribute to good local control. The accumulation of more clinical data is needed to further investigate the role of surgery in patients with advanced NSCLC harboring EGFR gene mutations.