Comparison of the Effects of OPRM1 A118G Polymorphism Using Different Opioids: A Prospective Study.

CONTEXT: µ-opioid receptor gene (OPRM1) A118G polymorphism (rs1799971) causes loss of N-glycosylation sites at the extracellular domain of µ-opioid receptors. G-allele carriers show a limited response to morphine; however, studies investigating the impact of A118G polymorphism on the efficacy of opioids other than morphine are limited. OBJECTIVE: To compare the impact of A118G polymorphism on the efficacy of various opioids. METHODS: This prospective cohort study enrolled 222 in-patients administered one of the following opioid therapies for cancer pain as part of an opioid introduction or rotation strategy: tapentadol extended-release tablets, methadone tablets, hydromorphone controlled-release tablets, oxycodone controlled-release tablets, or transdermal fentanyl patches. The impact of A118G polymorphism on the difference in the Brief Pain Inventory-Short Form score on days three, seven, and 14 from baseline was compared among the groups. RESULTS: Overall, 81, 74, and 67 patients had the AA, AG, and GG genotypes, respectively, with an OPRM1 A118G G-allele variant frequency of 0.47. The reduction in the Brief Pain Inventory-Short Form score after opioid therapy initiation did not differ significantly among the patients with the three A118G genotypes treated with tapentadol (p = 0.84) or methadone (p = 0.97), whereas it was significantly smaller in G-allele carriers than that in AA homozygous patients treated with hydromorphone (p < 0.001), oxycodone (p = 0.031), or fentanyl (p < 0.001). CONCLUSION: Tapentadol and methadone may be more suitable than hydromorphone, oxycodone, and fentanyl for G-allele carriers due to their dual mechanism of action and low susceptibility to OPRM1 A118G polymorphism.

Differences in the Analgesic Effect of Opioids on Pain in Cancer Patients With Spinal Metastases.

Background: Spinal metastasis pain includes both inflammatory and neuropathic pain, and opioids, which have only a µ-opioid receptor-stimulating effect, are generally less effective in neuropathic pain. However, no previous study has been conducted for the comparisons of the efficacy of opioids in treating spinal metastasis pain. Objective: To compare the efficacy of tapentadol and methadone with other opioids for back pain caused by a metastatic spinal tumor. Design: Retrospective cohort study. Setting/Subjects: A total of 274 patients were enrolled, who started a tapentadol extended-release tablet, methadone tablet, hydromorphone extended-release tablet, oxycodone extended-release tablet, or transdermal fentanyl patch for cancer pain due to spinal metastasis in Japan from January 1, 2013 to October 31, 2021. Measurements: The primary endpoint, the difference in the numerical rating scale (NRS) scores before and seven days after each opioid administration, was compared among the five groups. Results: In patients with numbness, a decrease of the NRS score on day seven compared with before starting each opioid was significantly higher in the tapentadol group than those in the hydromorphone, oxycodone, and fentanyl groups and comparable to that in the methadone group. In patients without numbness, no significant differences were observed in decreases of the NRS scores on day seven among the five groups. Conclusions: Tapentadol and methadone may be more effective than hydromorphone, oxycodone, and fentanyl for cancer pain due to spinal metastasis with numbness.

Referral pattern to nephrologist and prognosis in diabetic kidney disease patients: Single center retrospective cohort study.

BACKGROUND: Management of diabetic kidney disease (DKD) to prevent end-stage kidney disease (ESKD) has become a major challenge for health care professionals. This study aims to investigate the characteristics of patients with DKD when they are first referred to a nephrologist and the subsequent prognoses. METHODS: A total of 307 patients who were referred to our department from October 2010 to September 2014 at Osaka General Medical Center were analyzed. Independent risk factors associated with renal replacement therapy (RRT) and cardiovascular composite events (CVE) following their nephrology referral were later identified using Cox proportional hazards analysis. RESULTS: Of 307 patients, 26 (8.5%), 67 (21.8%), 134 (43.6%), and 80 (26.1%) patients were categorized as having chronic kidney disease (CKD) stages 3a, 3b, 4, and 5, respectively. The median estimated glomerular filtration rate (eGFR) and urinary protein levels were 22.3 mL/min/1.73 m2 and 2.83 g/gCr, respectively, at the time of the nephrology referral. During the follow-up period (median, 30 months), 121 patients required RRT, and more than half of the patients with CKD stages 5 and 4 reached ESKD within 60 months following their nephrology referral; 30% and <10% of the patients with CKD stages 3b and 3a, respectively, required RRT within 60 months following their nephrology referral. CONCLUSION: Patients with DKD were referred to nephrologist at CKD stage 4. Although almost half of the patients with CKD stage 5 at the time of nephrology referral required RRT within one-and-a-half years after the referral, kidney function of patients who were referred to nephrologist at CKD stage 3 and 4 were well preserved.

VGLL3 increases the dependency of cancer cells on de novo nucleotide synthesis through GART expression.

Vestigial-like family member 3 (VGLL3) is a member of the VGLL family that serves as cofactors for TEA-domain transcription factors. Although VGLL3 is involved in the proliferation of cancer cells, the molecular mechanisms underlying VGLL3-mediated cell proliferation remain largely unknown. In this study, we found that stable expression of VGLL3 in human lung cancer A549 cells affects glutamine metabolism and increases their dependency on de novo nucleotide synthesis for proliferation. Mechanistically, VGLL3 was found to induce the expression of GART, which encodes a trifunctional enzyme that catalyzes de novo purine synthesis from glutamine. GART knockdown and the glycinamide ribonucleotide synthase, aminoimidazole ribonucleotide synthase, and glycinamide ribonucleotide formyltransferase trifunctional protein (GART) inhibitor lometrexol repressed the proliferation and survival of A549 cells stably expressing VGLL3. Mesenchymal breast cancer BT549 cells and MDA-MB-231 cells showed high expression of VGLL3, and VGLL3 knockdown was found to reduce GART expression. Lometrexol also repressed the proliferation of these breast cancer cells, whereas addition of inosine monophosphate, an important metabolite downstream of GART, rescued this repression. Taken together, these results suggest that VGLL3 induces GART expression and thereby confers de novo nucleotide-dependent cell proliferation in cancer cells.

Duration of predialysis nephrological care and mortality after dialysis initiation.

BACKGROUND: The duration of predialysis nephrological care that can reduce all-cause and cardiovascular mortality after dialysis initiation has not been clarified. METHODS: A total of 1117 patients who started chronic dialysis treatment from 2006 to 2015 at Osaka General Medical Center were analyzed. Independent risk factors associated with all-cause and cardiovascular mortality after dialysis initiation and early death (death within 12 months after dialysis initiation) were identified using Cox proportional hazards analysis. Moreover, the duration of predialysis nephrology care that could reduce mortality was explored using several different definitions of early referral as well as "6 months" commonly used in previous studies. RESULTS: Of 1117 patients, 834 were referred 6 months before dialysis initiation. During the follow-up period (median, 34 months), 324 patients died after dialysis initiation. Although multivariate Cox analysis did not show a favorable association between early referral of "6 months before dialysis initiation" and all-cause and cardiovascular mortality, 20-month predialysis nephrological care was associated with better first-year overall survival after dialysis initiation (hazard ratio 0.58; 95% confidence interval 0.35-0.98; P = 0.040). CONCLUSION: More than 6 months nephrological care before dialysis initiation was not early enough to reduce all-cause and cardiovascular mortality after dialysis initiation. Our results suggest that nephrology referral 20 months before dialysis initiation would be necessary to reduce first-year overall survival after dialysis initiation.

Two cases of air leak syndrome after bone marrow transplantation successfully treated by the pleural covering technique.

Air leak syndrome (ALS) is a rare complication after bone marrow transplantation (BMT) and usually has a fatal outcome because of the high recurrence rate and treatment-refractory nature. A 32-year-old man with a history of BMT for acute lymphoblastic leukemia suffered from metachronous bilateral ALS. Bullectomy and the pleural covering procedure (PLC) were successfully performed for each side of the thorax. After surgery, no relapse of pneumothorax was seen for 2 years on the right side and for 1 year on the left side. A 38-year-old man with a history of BMT for acute myelogenous leukemia (AML) suffered from ALS at the thorax on the left side. Bullectomy and the PLC were successfully performed. After that no recurrence of left pneumothorax for 7 years. We experienced two cases of ALS after BMT successfully treated by the PLC. This technique may be a viable treatment option for future lung transplantation.

Air leak pattern shown by digital chest drainage system predict prolonged air leakage after pulmonary resection for patients with lung cancer.

BACKGROUND: A common cause of complications after a pulmonary resection procedure is prolonged air leakage. Recently introduced digital drainage systems provide accurate recording of air leak data for later review. We investigated the clinical usefulness of the continuous stream of data recorded by such a device. METHODS: We analyzed data obtained from 299 patients with pulmonary malignancy who underwent a pulmonary resection procedure for lung cancer patients with use of a digital chest drainage system. Postoperative air leak patterns were divided into 4 groups and their correlation with prolonged air leakage after pulmonary resection was evaluated. RESULTS: The incidence of prolonged air leak was 10% (30/299). The postoperative air leak patterns noted in the present patients were divided into none (n=217, 73%), intermittent (n=21, 7%), decrease (n=40, 13%), and variable (n=21, 7%). The incidence of prolonged air leak in each group was 0.5% (1/217) in the none group, 24% (5/21) in the intermittent group, 20% (8/40) in the decrease group, and 76% (16/21) in the variable group. The amount of air leakage immediately after surgery was highest in the variable group. Patients in the intermittent and variable groups had longer durations of air leakage and chest tube placement. The frequency of postoperative interventional treatment was significantly higher in the variable group as compared to the others. Chest tube reinsertion for pneumothorax and increased subcutaneous emphysema after the initial chest tube removal was only seen in the intermittent group. CONCLUSIONS: Advantages of digital drainage system use are continuous monitoring and recording capabilities, which show the detailed air leak pattern after pulmonary resection. That pattern can be used to predict the durations of air leakage and chest tube drainage, as well as for producing an air leak management algorithm.

Carnosol suppresses interleukin-6 production in mouse lungs injured by ischemia-reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide.

Carnosol is a naturally occurring herbal compound, known for its antioxidative properties. We previously found that carnosol protected mouse lungs from ischemia-reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms underpinning carnosol-mediated lung protection, we analyzed modes of interleukin-6 (IL-6) gene expression, which is associated with lung ischemia-reperfusion injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were elevated in the mouse lungs subjected to clamp-reperfusion, which was associated with elevated levels of other inflammatory modulators, such as activating transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein levels in mouse lung homogenates prepared after the clamp-reperfusion. On the other hand, the ATF3 gene expression was negatively correlated with that of IL-6 in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells were subjected to hypoxia-reoxygenation, carnosol treatment lowered oxygen consumption after reoxygenation, which was coupled with a correlation with a transient production of mitochondrial reactive oxygen species and following ATF3 gene expression. These results suggest that carnosol treatment could be a new strategy for protecting lungs from ischemia-reperfusion injury by modulating the ATF3-IL-6 axis.

Aggressive Surgical Resection of Pulmonary Artery Intimal Sarcoma.

Intimal sarcoma of the pulmonary artery is a rare and highly malignant neoplasm. This report describes a case of a 30-year-old woman with an extensive right pulmonary artery tumor who underwent an emergency operation. The tumor was aggressively resected with right pneumonectomy and reconstruction of the right ventricle outflow tract and left pulmonary artery. Although the resected margin at the left pulmonary artery was positive for disease, as confirmed by mouse double minute type 2 homologue staining, she is doing well and remains free of relapse at 16 months after the operation.

Stromal PDGFR-ß Expression is Associated with Postoperative Survival of Non-Small Cell Lung Cancer Patients Receiving Preoperative Chemo- or Chemoradiotherapy Followed by Surgery.

BACKGROUND: PDGFR-ß is used as a stromal biomarker and is functional in mesenchymal cells of the tumor microenvironment. The significance of stromal PDGFR-ß expression in non-small cell lung cancer (NSCLC) in patients undergoing preoperative chemo- or chemoradiotherapy had not been determined. METHODS: Patients with NSCLC undergoing preoperative chemo- or chemoradiotherapy between 1996 and 2014 were assessed for expression of stromal PDGFR-ß by immunohistochemistry using resected specimens. Relationships between stromal PDGFR-ß expression and survival after operation were analyzed. Forty-three patients who underwent surgery without preoperative treatment in 2005 were also analyzed as a chemo-naïve control group. RESULTS: The mean age of the 92 patients was 60.2 years. Seventy-eight (85%) were male, and 14 (15%) were female. Fifty-four patients (59%) underwent preoperative chemoradiotherapy, and 38 patients (41%) underwent preoperative chemotherapy. Regimens for preoperative chemotherapy were cisplatin (CDDP) based in 48 patients (52%) and carboplatin (CBDCA) based in 43 (42%). While stromal cells expressed PDGFR-ß in 21 chemo-naïve patients (49%), stromal cells expressed PDGFR-ß in 65 patients who underwent preoperative therapy (p = 0.02). The 5-year disease-free survival rate (DFS) of the PDGFR-ß-positive group was significantly worse than that of the negative group (27 vs. 48%, p = 0.04). The 5-year disease-specific survival rate (DSS) in the stromal PDGFR-ß-positive group was also significantly worse than in the negative group (43 vs. 70%, p = 0.01). On the other hand, stromal PDGFR-ß expression did not influence survival in chemo-naïve patients. CONCLUSIONS: Stromal PDGFR-ß expression is negatively associated with DFS and DSS in patients with NSCLC undergoing preoperative chemo- or chemoradiotherapy.

Gas6 derived from cancer-associated fibroblasts promotes migration of Axl-expressing lung cancer cells during chemotherapy.

Alterations to the tumor stromal microenvironment induced by chemotherapy could influence the behavior of cancer cells. In the tumor stromal microenvironment, cancer-associated fibroblasts (CAFs) play an important role. Because the receptor tyrosine kinase Axl and its ligand Gas6 could be involved in promoting non-small cell lung cancer (NSCLC), we investigated the role of Gas6 secreted by CAFs during chemotherapy in NSCLC. In a murine model, we found that Gas6 expression by CAFs was upregulated following cisplatin treatment. Gas6 expression might be influenced by intratumoral hypoperfusion during chemotherapy, and it increased after serum starvation in a human lung CAF line, LCAFhTERT. Gas6 is associated with LCAFhTERT cell growth. Recombinant Gas6 promoted H1299 migration, and conditioned medium (CM) from LCAFhTERT cells activated Axl in H1299 cells and promoted migration. Silencing Gas6 in LCAFhTERT reduced the Axl activation and H1299 cell migration induced by CM from LCAFhTERT. In clinical samples, stromal Gas6 expression increased after chemotherapy. Five-year disease-free survival rates for patients with tumor Axl- and stromal Gas6-positive tumors (n = 37) was significantly worse than for the double negative group (n = 12) (21.9% vs 51.3%, p = 0.04). Based on these findings, it is presumed that Gas6 derived from CAFs promotes migration of Axl-expressing lung cancer cells during chemotherapy and is involved in poor clinical outcome.

Chemotherapy enhances programmed cell death 1/ligand 1 expression via TGF-ß induced epithelial mesenchymal transition in non-small cell lung cancer.

In cancer immunology, the programmed cell death 1-programmed cell death 1/ligand 1 (PD-1/PD-L1) pathway plays a major role. Anti-PD-1 and anti-PD-L1 antibodies provide reliable immunotherapy when given as treatment for various types of malignancy including lung cancer. PD-L1 expression in cancer cells has been reported to be a predictive factor for the therapeutic effects of immunotherapy. However, the mechanism of PD-L1 expression remains unclear. Another key process in cancer progression is epithelial-mesenchymal transition (EMT). In the present study, we investigated the mechanism of PD-L1 expression as well as changes in its expression during the EMT process in non-small cell lung cancer (NSCLC). In this study, A549 cells underwent EMT by treatment with TGF-ß or chemotherapeutic agents and then PD-L1 expression was evaluated. The alterations of PD-L1 expression was also examined during the reverse EMT process; mesenchymal-epithelial transition (MET). The relationship between for PD-L1 expression and EMT status in clinical specimens with NSCLC after induction chemotherapy were analyzed by immunohistochemical staining. We found that PD-L1 expression was upregulated following TGF-ß induction; in contrast, it was downregulated by TGF-ß receptor-kinase inhibitors and the MET process. Furthermore, chemo-treatment increased TGF-ß expression and enhances PD-L1 expression via autocrine TGF-ß induced EMT. Analysis of clinical samples revealed a significant relationship between PD-L1 expression and EMT status (P<0.05). In conclusion, our results suggest that PD-L1 expression is regulated by TGF-ß induced EMT and enhanced by chemo-treatment via the chemo-induced TGF-ß signaling. The anti-PD-1/PD-L1 blockade may provide more effective anticancer activities in combination with chemotherapy in NSCLC.

Surgical resection for advanced lung cancer using the hemi-clamshell approach.

OBJECTIVES: The hemi-clamshell (HCS) approach consists of partial sternotomy with antero-lateral thoracotomy. This study evaluated the utilities and outcomes of the HCS approach in advanced lung cancer patients. METHODS: We retrospectively investigated 45 patients who underwent surgery for advanced lung cancer via the HCS procedure between 2000 and 2014, the indications for surgery being tumour invasion extending to the aorta arch in 5, descending aorta in 9, main pulmonary artery in 5, superior vena cava in 6, right or left atrium in 4, apical thoracic dome in 7 patients and mediastinal lymphadenopathy for left-sided lung cancer in 12. Preoperative chemo-radiation induction therapy was given to 33 of these patients. RESULTS: We performed 34 lobectomies, including 8 sleeve lobectomies, 10 pneumonectomies and 1 wedge resection of the lung. Cardiovascular reconstruction of the aortic arch was performed in 3, descending aorta in 4, subclavian arteries in 4, superior vena cava in 5, atrial wall in 4 and pulmonary artery in 12 patients with some overlap. En bloc chest wall resection was performed in 7 patients. Lymphadenectomy in the pre-tracheal and subcarinal areas was routinely performed. Forty-two operations (93%) were complete resections. No postoperative mortalities occurred and the 5-year survival rate for all patients was 53%. CONCLUSIONS: The HCS approach is suitable for advanced lung cancer, including invasion of mediastinal structures, the apical dome and mediastinal lymph nodes. It provides a wide view of the mediastinum and apex of the chest, and safe access to the thoracic great vessels, resulting in better long-term survival rates.

Pirfenidone plays a biphasic role in inhibition of epithelial-mesenchymal transition in non-small cell lung cancer.

INTRODUCTION: Epithelial to mesenchymal transition (EMT) relates to both organ fibrosis and malignant behavior of cancer. Pirfenidone (PFD) is an anti-fibrotic agent for idiopathic pulmonary fibrosis and one of its functions may be to inhibit fibrotic EMT. This study aimed to investigate the possibility that PFD might exert an anti-tumor effect through inhibition of EMT in non-small cell lung cancer (NSCLC) cell lines in vitro and in vivo. METHODS: NSCLC cells (A549, NCI-H358) were used to evaluate PFD effects on TGF-ß1 induced phenotypic changes. Possible TGF-ß1 signaling pathways modulated by PFD were evaluated. The effects of PFD on EMT induced by an anti-cancer drug was also analyzed. The impact of PFD on tumor growth in nude mice as well as on EMT change in vivo was also determined. RESULTS: PFD significantly inhibited TGF-ß1-induced EMT. Smad2 phosphorylation and TGF-ß1 receptor I expression were also inhibited as was translocation of Smad2 from the cytoplasm into the nucleus. Carboplatin induced elevation of TGF-ß1 production from cancer cells together with induction of EMT, which were suppressed by co-treatment with PFD. In in vivo examination, PFD alone did not inhibit tumor progression whereas its combination with carboplatin significantly decreased tumor growth. Immunohistological analysis showed that PFD suppressed EMT change induced by carboplatin. CONCLUSIONS: PFD could attenuate the EMT process induced not only by exogenous TGF-ß1 but also by paracrine TGF-ß produced from NSCLC cells. PFD may be a promising new therapeutic agent for the treatment of NSCLC through the regulation of EMT.

Role of pulmonary metastasectomy in colorectal cancer in the era of modern multidisciplinary therapy.

PURPOSE: To clarify the role of pulmonary metastasectomy in colorectal cancer in the era of modern multidisciplinary therapy. METHODS: The characteristics and outcomes of the patients who underwent pulmonary metastasectomy for colorectal cancer through 2002 (n = 26) and from 2003 (n = 68) were compared. RESULTS: The patients treated from 2003 had a smaller tumor size and more frequently had a history of extra-pulmonary relapses than did those treated through 2002. There was a significant improvement in the 5-year overall survival (42.0% vs. 73.1%, p = 0.03) but not the 5-year relapse-free survival (41.4% vs. 37.5%, p = 0.85) after pulmonary metastasectomy from 2003. The rate of patients who received local therapy with curative intent after the first pulmonary metastasectomy was significantly higher in patients treated from 2003 than in those treated through 2002 [4/13, (31%) vs. 25/39 (64%), p = 0.04]. The survival after relapse after the first pulmonary metastasectomy was significantly longer in patients treated from 2003 than in those treated through 2002 (median survival time: 14 vs. 47 months). CONCLUSIONS: Pulmonary metastasectomy for colorectal cancer remains an important treatment option in the sense that it can achieve a good relapse-free survival.

Surgery for malignant pulmonary nodules in patients with a history of oesophageal cancer.

Objectives: The objective of this study is to analyse the short- and long-term results of surgery for malignant pulmonary nodules in patients with a history of oesophageal cancer (EC) in order to assess the significance of surgery in these patients. Methods: The data of 28 consecutive patients with a history of EC who underwent pulmonary resection for malignant pulmonary nodules were reviewed. The perioperative and long-term results were analysed. Results: The histological type of oesophageal cancer was squamous cell carcinoma in all of the patients. The preceding treatments for EC were surgery with or without neoadjuvant therapy in 21, chemoradiotherapy in 4 and endoscopic resection in 3. The patients were smokers, with low body mass indices, and had high incidences of a history of malignancy besides EC and other comorbidities. Complete resection was achieved in 27 patients (96%). There was no perioperative mortality and 7 patients (25%) developed postoperative complications. Based on the pathological and clinical criteria, 14 patients (50%) were diagnosed with primary lung cancer, 10 patients (35%) with pulmonary metastases from EC and 4 patients (25%) with pulmonary metastasis from another cancer. The 5-year disease-free and overall survival rates of all patients were 48% and 60%, respectively. Conclusions: Surgery for malignant pulmonary nodules in patients with a history of EC can be performed with acceptable surgical risk despite the high rate of comorbid illness in these patients. Proactive surgical management should be considered for treating malignant pulmonary nodules in patients with a previous history of EC as this strategy provides favourable long-term results.

Outcomes of lung cancer surgery in patients with coronary artery disease: a decade of experience at a single institution.

PURPOSE: The aim of this study is to investigate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with coronary artery disease (CAD). METHODS: Among 805 patients who underwent surgery for NSCLC at our hospital within a recent 10-year period, 43 (5.3 %) had a history of CAD. We analyzed the surgical outcomes and risk factors for postoperative complications in these 43 patients. RESULTS: The postoperative mortality and morbidity rates were 2 and 42 %, respectively. The morbidity rate was significantly higher in the patients with CAD than in those without CAD (P < 0.01). Postoperative cerebrovascular or cardiovascular events occurred in four patients (9 %). Having two of the following was significantly associated with the development of postoperative complications: decreased cardiac function, respiratory dysfunction, or deteriorated renal function (p = 0.04). The 5-year overall and disease-free survival rates of the patients with CAD were 75.6 and 64.5 %, respectively; comparable with those of the patients without CAD; at 77.9 % and 72.5 %, respectively (p = 0.46 and 0.69). CONCLUSIONS: Patients with NSCLC and a history of CAD are at higher risk of complications after pulmonary resection. Combined decreased organ function is a risk factor for postoperative complications. CAD did not influence the long-term outcomes of patients after pulmonary resection for NSCLC.

Outcomes of surgery for lung cancer in patients with atrial fibrillation as a preoperative comorbidity: a decade of experience at a single institution in Japan.

PURPOSE: To investigate the surgical outcomes of surgery for non-small cell lung cancer (NSCLC) in patients with atrial fibrillation (AF) as a preoperative comorbidity. METHODS: Among 805 patients who underwent surgery for NSCLC, 27 (3.4%) had a history of AF. We analyzed the perioperative and long-term outcomes of these 27 patients. RESULTS: Fourteen patients (52%) had chronic AF and 13 (48%) had paroxysmal AF; being high rates of a comorbid illness. Nineteen patients (70%) underwent lobectomy, and 8 (30%) underwent sublobar resection. Ten patients (37%) received perioperative heparinization. There was no mortality. Other non-AF postoperative complications developed in 8 patients (30%), this incidence being higher than among the patients without AF (16%, 127 out of 778, p = 0.09). A thromboembolic event occurred in one patient (4%). With respect to the long-term outcomes, the 5-year overall survival and disease-free survival rates among the patients with AF were 70.3 and 60.8%, respectively, which were similar to those in the patients without AF (79.8 and 72.6%, p = 0.30 and 0.31). CONCLUSIONS: Lung cancer surgery in patients with AF is safe and provides favorable long-term outcomes; however, thoracic surgeons should monitor these patients carefully for postoperative thromboembolic events.

Late-Onset Pulmonary Fistula after Resection of Pulmonary Metastasis from Colorectal Cancer Following Perioperative Chemotherapy with Bevacizumab.

Chemotherapy with bevacizumab followed by surgery is now a viable treatment option for pulmonary metastasis from colorectal cancer (CRC). We herein report two cases of late-onset pulmonary fistula after resection of pulmonary metastasis from CRC following perioperative chemotherapy with bevacizumab. One patient suffered from a late-onset pulmonary fistula that occurred 3 months after pulmonary resection, which was treated with chest drainage and pleurodesis. The other patient suffered from a pulmonary fistula after three cycles of chemotherapy with bevacizumab after pulmonary resection, and underwent surgery to treat the fistula.