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.

Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101).

BACKGROUND: Adjuvant oral uracil-tegafur (UFT) has led to significantly longer postoperative survival among patients with non-small-cell lung cancer (NSCLC). Gemcitabine (GEM) monotherapy is also reportedly effective for NSCLC and has minor adverse events (AEs). This study compared the efficacy of GEM- versus UFT-based adjuvant regimens in patients with completely resected pathological stage (p-stage) IB-IIIA NSCLC. PATIENTS AND METHODS: Patients with completely resected p-stage IB-IIIA NSCLC were randomly assigned to GEM or UFT. The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and AEs. RESULTS: We assigned 305 patients to the GEM group and 303 to the UFT group. Baseline factors were balanced between the arms. Of the 608 patients, 293 (48.1%) had p-stage IB disease, 195 (32.0%) had p-stage II disease and 121 (19.9%) had p-stage IIIA disease. AEs were generally mild in both groups, and only one death occurred, in the GEM group. After a median follow-up of 6.8 years, the two groups did not significantly differ in survival: 5 year OS rates were GEM: 70.0%, UFT: 68.8% (hazard ratio 0.948; 95% confidence interval 0.73-1.23; P = 0.69). CONCLUSION: Although GEM-based adjuvant therapy for patients with completely resected stage IB-IIIA NSCLC was associated with acceptable toxicity, it did not provide longer OS than did UFT.

Preoperative AminoIndex Cancer Screening (AICS) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer.

BACKGROUND: AminoIndex™ Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC). METHODS: Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed. RESULTS: The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6 years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p = 0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p = 0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma. CONCLUSION: Preoperative AICS (lung) rank C is a high-risk predictor of postoperative recurrence in patients undergoing curative resection for NSCLC.

[Perioperative Management for Patients Undergoing General Thoracic Surgery with Metabolic or Endocrine Disorders].

By improvement of surgical procedures and advances in perioperative management, the patients with various comorbidity diseases have been able to undergo pulmonary resection. In particular, the patients with endocrine and metabolic disorders are relatively frequent and often underwent pulmonary resection. Most of them are chronic diseases and often controlled for a long time. However, they sometimes have drastic changes due to surgical stress during perioperative periods. Failure to properly perioperative management for them may result in postoperative morbidity or mortality. Therefore, we have to well know perioperative changes by surgical stress for them. Among endocrine and metabolic disorders, following is frequent, diabetes, hyperthyroidism and hypothyroidism, steroid administration. We describe perioperative management of them. When operating on them, it is important to ① proper evaluation before surgery, ② careful postoperative management, and ③ close coordination with the department of endocrinology and anesthesiology.

[A Patient with Rectal Cancer and Multiple Lung Metastases Treated with XELOX plus Bevacizumab (Bev) Therapy].

The patient was a 76-year-old woman who underwent laparoscopic-assisted low anterior resection for rectal cancer. According to the Japanese classification of colorectal carcinoma (8th Edition), the tumor was tub1, ly0, v0, and pStage Ⅰ (pT1bN0M0), Cur A. She received no adjuvant chemotherapy. A chest CT scan obtained 42 months after the surgery revealed 3 lung metastases in the left lung, with the biggest measuring 12 mm; the CA19-9 level was elevated to 72U/mL (normal≦38 U/mL). She declined surgery for the recurrence. She was treated with XELOX plus bevacizumab (Bev) therapy. Before XELOX plus Bev, the 3 lung metastases had enlarged, with the biggest now measuring 15 mm, and the CA19-9 level was elevated to 166 U/mL. After 4 cycles, the lung metastases decreased in size and the CA19-9 level decreased to 4 U/mL. We did not perform pulmonary resection or additional chemotherapy. No progression of the recurrent tumors was detected on CT after 2 years, and the CA19-9 level was within the normal range. XELOX plus Bev therapy may be effective for unresectable pulmonary metastasis from colorectal cancer.

Differentiation of lung neoplasms with lepidic growth and good prognosis from those with poor prognosis using computer-aided 3D volumetric CT analysis and FDG-PET.

BACKGROUND: Many studies have reported that transverse computed tomography (CT) imaging findings correlate with prognosis of patients with small peripheral lung neoplasm with lepidic growth. However, no studies have examined this correlation with the aid of three-dimensional (3D) CT data. PURPOSE: To determine the most efficacious imaging factor for differentiation of lepidic growth type lung neoplasms with good prognosis from those with poor prognosis. MATERIAL AND METHODS: We evaluated CT findings, nodule patterns, SUVmax on FDG-PET/CT, as well as nodule volume and ratios of solid parts to nodule volume that were semi-automatically measured on CT images of 64 pulmonary nodules of ≤ 2 cm in 60 consecutive patients (24 men and 36 women; mean age, 65 years). For logistic modeling, we used all of the significant factors observed between the neoplasms with good and with poor prognosis as independent variables to estimate the statistically significant factors for discriminating invasive adenocarcinomas with lepidic growth (lesions with poor prognosis, n=42) from the other neoplasms, including preinvasive lesions (lesions with good prognosis, n=22), resulting in a recommendation for the optimal criterion for predicting lesions with poor prognosis. RESULTS: The logistic regression model identified the ratio of the solid part to the whole volume of a pulmonary nodule as the only significant factor (P=0.04) for differentiating lepidic growth type lung neoplasms with good prognosis from those with poor prognosis. A ratio of 0.238 or more showed the highest discriminatory accuracy of 84% with 91% sensitivity and 76% specificity. CONCLUSION: Computer-aided analyses of pulmonary nodules proved most useful for establishing the optimal criterion for differentiation of lepidic growth type lung neoplasms with good prognosis from those with poor prognosis.

Thin-section CT findings in peripheral lung cancer of 3 cm or smaller: are there any characteristic features for predicting tumor histology or do they depend only on tumor size?

BACKGROUND: Ground-glass opacity (GGO) is reported to be characteristic to lepidic growth of neoplasm in subsolid nodules. In solid nodules of lung cancer, however, there is no characteristic feature to be reported. PURPOSE: To study if there are any thin-section CT findings characteristic to tumor histology or if they are only related to tumor size in solid nodules of the lung cancer. MATERIAL AND METHODS: This study included 106 solid peripheral lung cancers of 3 cm or smaller (56 adenocarcinomas, 33 squamous cell carcinomas, and 17 small cell carcinomas) in which 16-slice CT with 1 mm collimation was performed before surgery. Six morphologic findings (presence or absence of lobulation, coarse spiculation, air bronchogram, cavity, pleural tag, and pleural-based lesion) and four measurements (ratio of the greatest transverse and vertical diameter to the shortest transverse diameter and density of lobulation and coarse spiculation) on thin-section CT images were evaluated. Density of lobulation (coarse spiculation) was defined as the ratio of lobulation (coarse spiculation) number to the greatest transverse diameter of a nodule. RESULTS: Air bronchogram (P < 0.01) was the only significant factor for predicting lung adenocarcinoma. The prevalence of air bronchogram was significantly greater in adenocarcinoma than in squamous cell carcinoma (P < 0.01) or small cell carcinoma (P < 0.01). As the tumor size advanced, significantly positive linear trends were seen in the prevalence of lobulation (P < 0.01), coarse spiculation (P < 0.01), and pleural tag (P < 0.01), and the mean values of density of lobulation (P < 0.01) and coarse spiculation (P < 0.01), while the significant negative linear trend was seen in the ratio of vertical diameter to the shortest transverse (P = 0.02). CONCLUSION: Air bronchogram on thin-section CT is characteristic feature of solid adenocarcinoma of the lung. However, other thin-section CT findings are irrelevant to tumor histology and related only to tumor size.

Prognosis associated with surgery for non-small cell lung cancer and synchronous brain metastasis.

PURPOSE: Several reports have described extended survival after aggressive surgical treatment for non-small cell lung cancer (NSCLC) and synchronous brain metastasis. This retrospective analysis assesses the prognostic factors in this population. METHODS: We reviewed retrospectively the medical records of 29 patients with synchronous brain metastasis from NSCLC, who underwent surgical treatment in our institution between 1980 and 2008. All patients underwent chest surgery to remove the primary lesion. The impact of several variables on survival was assessed. RESULTS: The median follow-up period was 9.6 months and the 5-year survival rate from the time of lung cancer resection was 20.6 %. Univariate analysis demonstrated that the carcinoembryonic antigen (CEA) level, primary tumor size, and the presence of lymph node involvement were predictive of overall survival (p < 0.05). Multivariate analysis also identified those factors to be independent favorable prognostic factors. CONCLUSIONS: Although the survival of patients with brain metastasis from non-small cell lung cancer remains poor, surgical resection may benefit a select group of patients, particularly those with a normal CEA level, small tumor size, and node-negative status.

The Impact of Kinlessness on Survival in Patients With Advanced Non-small Cell Lung Cancer: A Single-Center Retrospective Study.

Objectives Among patients with advanced non-small cell lung cancer (NSCLC), there are those who do not have a spouse, family members, or friends to support them in their cancer treatment and daily life: the kinless patients. Therefore, we designed an exploratory study of kinlessness and the prognosis of advanced NSCLC. Methods We retrospectively analyzed the prognosis of clinical factors and treatment and kinlessness in patients with advanced NSCLC with wild-type or unknown status for epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK) and who visited our hospital from November 2018 to February 2023. In addition to the survival analysis by kinlessness, a multivariable analysis of survival was performed for all clinical factors. In a secondary analysis, a multivariable analysis of the choice of best supportive care (BSC) was performed for all clinical factors. Results One hundred forty-four patients are included in our cohort. There were 131 patients with kin, with a median survival of 1.34 years (95% CI of 1.01-1.79 years). There were 13 patients has no kin, with a median survival of 0.53 years (95% CI 0.23-0.76 years). The log-rank analysis showed that kinless patients had significantly shorter overall survival than patients who have kin. A Cox regression analysis showed that age, distant metastasis, performance status, and kinlessness were associated with overall survival. Secondary analysis showed that there was no statistical association between kinlessness and the choice of BSC in our cohort. Conclusions Kinless patients had shorter survival than patients who have kin in our single-center, retrospective study of patients with advanced NSCLC with wild-type or unknown status for (EGFR/ALK). Further research to evaluate the clinical impact of kinlessness in the treatment of advanced NSCLC is needed.

The significance and robustness of a plasma free amino acid (PFAA) profile-based multiplex function for detecting lung cancer.

BACKGROUND: We have recently reported on the changes in plasma free amino acid (PFAA) profiles in lung cancer patients and the efficacy of a PFAA-based, multivariate discrimination index for the early detection of lung cancer. In this study, we aimed to verify the usefulness and robustness of PFAA profiling for detecting lung cancer using new test samples. METHODS: Plasma samples were collected from 171 lung cancer patients and 3849 controls without apparent cancer. PFAA levels were measured by high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). RESULTS: High reproducibility was observed for both the change in the PFAA profiles in the lung cancer patients and the discriminating performance for lung cancer patients compared to previously reported results. Furthermore, multivariate discriminating functions obtained in previous studies clearly distinguished the lung cancer patients from the controls based on the area under the receiver-operator characteristics curve (AUC of ROC = 0.731 ~ 0.806), strongly suggesting the robustness of the methodology for clinical use. Moreover, the results suggested that the combinatorial use of this classifier and tumor markers improves the clinical performance of tumor markers. CONCLUSIONS: These findings suggest that PFAA profiling, which involves a relatively simple plasma assay and imposes a low physical burden on subjects, has great potential for improving early detection of lung cancer.

Cytoreductive surgery and post-operative heated pleural chemotherapy for the management of pleural surface malignancy.

PURPOSE: We retrospectively analysed the long-term outcomes of cytoreductive surgery and post-operative heated pleural chemotherapy (HPC) for thoracic malignancies with pleural spread. MATERIALS AND METHODS: Between 1987 and 2010, 160 patients were enrolled. There were 101 patients with non-small cell lung cancer (NSCLC), 25 with malignant pleural mesothelioma (MPM), 12 with thymoma, and 22 with tumours metastatic to the lung and pleura. Immediately after intra-thoracic administration of cisplatin or carboplatin, hyperthermia was performed by using an 8.00 MHz radiofrequency capacitive heating device for 1 to 4 courses in each patient. RESULTS: There was no systemic toxicity or treatment-related mortality. Five-year overall survival rates were 37.4% in NSCLC, 15.9% in MPM, 91.7% in thymoma, and 25.8% in metastatic lung tumour. Five-year local relapse-free survival (RFS) rates were 55.2% in NSCLC, 24.4% in MPM, 64.8% in thymoma, and 27.2% in tumours metastatic to the lung and pleura. When 101 NSCLCs were categorised into pleural lavage cytology positive (grade 1: n = 37), limited extent of carcinomatous pleuritis (grade 2: n = 21), and extensive carcinomatous pleuritis (grade 3: n = 43), 5-year overall survival rates were 62.5%, 49.2%, and 13.6%, respectively. The local RFS was significantly better in group 1/2 than in group 3. CONCLUSIONS: Although our study has some of the usual weaknesses of a single institution retrospective study, cytoreductive surgery and HPC are feasible and safe. It is suggested that HPC may have a potential role for local control as adjuvant treatment for cytoreductive surgery in patients with minor pleural spread.

F18-FDG PET-CT analyses of small peripheral adenocarcinoma of the lung.

BACKGROUND: Radiological discrimination of histologic subtypes of small peripheral adenocarcinoma of the lung is clinically important. Although there are many articles in which CT findings were used for this purpose, there are only a few reports on the capability of FDG PET-CT findings for histologic classification of this tumor. PURPOSE: To investigate the correlation between visual assessment or maximum standard uptake values (SUVmax) on F18-FDG PET-CT and histology grading of small peripheral adenocarcinoma of the lung. MATERIAL AND METHODS: Proportions of positive PET-CT diagnoses and SUVmax were retrospectively reviewed on 96 solitary pulmonary nodules of ≤2 cm in 90 consecutive patients. Tumors were classified into four groups according to Noguchi's classification (group 1 [n = 10], atypical adenomatous hyperplasia and type A tumors; group 2 [n = 12], type B tumors; group 3 [n = 42], type C tumors; group 4 [n = 32], types D, E, and F tumors). Proportions of positive PET-CT diagnoses and mean SUVmax of lesions among four groups were compared using trend tests to examine if there is a significant linear correlation with the progression of the histology grading of tumors. Then, an optimal threshold of SUVmax was proposed to best discriminate tumors of poor (groups 3 and 4) from good (groups 1 and 2) prognosis. RESULTS: There was a significant linear trend for both visual assessment (P < 0.01) and SUVmax (P < 0.01). A SUVmax of 0.42 showed the highest accuracy of 84% with 95% sensitivity and 50% specificity for predicting tumors of poor prognosis. A SUVmax of 2.05 showed 100% specificity with 49% sensitivity, and 60% accuracy. Positive visual diagnoses showed accuracy of 83% with 90% sensitivity and 59% specificity. CONCLUSION: Visual assessment and SUVmax on PET-CT correlated well with the histology grading of small peripheral adenocarcinoma of the lung.

Analytical Performance of a Highly Sensitive System to Detect Gene Variants Using Next-Generation Sequencing for Lung Cancer Companion Diagnostics.

The recent increase in the number of molecular targeted agents for lung cancer has led to the demand for the simultaneous testing of multiple genes. Although gene panels using next-generation sequencing (NGS) are ideal, conventional panels require a high tumor content, and biopsy samples often do not meet this requirement. We developed a new NGS panel, called compact panel, characterized by high sensitivity, with detection limits for mutations of 0.14%, 0.20%, 0.48%, 0.24%, and 0.20% for EGFR exon 19 deletion, L858R, T790M, BRAF V600E, and KRAS G12C, respectively. Mutation detection also had a high quantitative ability, with correlation coefficients ranging from 0.966 to 0.992. The threshold for fusion detection was 1%. The panel exhibited good concordance with the approved tests. The identity rates were as follows: EGFR positive, 100% (95% confidence interval, 95.5-100); EGFR negative, 90.9 (82.2-96.3); BRAF positive, 100 (59.0-100); BRAF negative, 100 (94.9-100); KRAS G12C positive, 100 (92.7-100); KRAS G12C negative, 100 (93.0-100); ALK positive, 96.7 (83.8-99.9); ALK negative, 98.4 (97.2-99.2); ROS1 positive, 100 (66.4-100); ROS1 negative, 99.0 (94.6-100); MET positive, 98.0 (89.0-99.9); MET negative 100 (92.8-100); RET positive, 93.8 (69.8-100); RET negative, 100 (94.9-100). The analytical performance showed that the panel could handle various types of biopsy samples obtained by routine clinical practice without requiring strict pathological monitoring, as in the case of conventional NGS panels.

Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non-Small-Cell Lung Cancer With EGFR Mutation (IMPACT).

PURPOSE: To investigate the efficacy of gefitinib as an adjuvant therapy for non-small-cell lung cancer patients with EGFR mutation. PATIENTS AND METHODS: IMPACT (WJOG6410L; University Hospital Medical Information Network Clinical Trials Registry: UMIN000006252), a randomized, open-label, phase III study, included patients with completely resected pathologic stage II-III non-small-cell lung cancer harboring EGFR mutations (exon 19 deletion or L858R) during September 2011 to December 2015. Patients were randomly assigned to receive gefitinib (250 mg once daily) for 24 months or cisplatin (80 mg/m2 on day 1) plus vinorelbine (25 mg/m2 on days 1 and 8; cis/vin) once every 3 weeks for four cycles. The primary end point was disease-free survival (DFS). RESULTS: Overall, 234 patients were randomly assigned. Among 232 eligible patients (116 each; excluding two who withdrew consent), the median DFS was 35.9 and 25.1 months in the gefitinib and cis/vin groups, respectively. However, Kaplan-Meier curves crossed around 4 years after surgery with no statistically significant difference (stratified log-rank P = .63; hazard ratio by stratified Cox proportional hazards model = 0.92; 95% CI, 0.67 to 1.28). Overall survival (OS) was also not different (stratified log-rank P = .89; hazard ratio = 1.03; 95% CI, 0.65 to 1.65), with the 5-year OS rates being 78.0% and 74.6% in the gefitinib and cis/vin groups, respectively. Treatment-related deaths occurred in 0 and three patients in the gefitinib and cis/vin groups, respectively. CONCLUSION: Although adjuvant gefitinib appeared to prevent early relapse, it did not prolong DFS or OS. However, similar DFS and OS may justify adjuvant gefitinib in the selected patient subsets, especially those deemed ineligible for platinum-doublet adjuvant therapy; however, this was not a noninferiority trial.

Surgical resection of pulmonary metastases from meningioma: report of a case.

Meningiomas rarely metastasize, and little information on pulmonary metastasectomy from meningioma has been documented. We herein report a case of a potentially curative resection for meningioma that metastasized to the lung. A 67-year-old woman was admitted to our hospital because of two masses in the right lung. In 1993, when the patient was 52 years old, she underwent a craniotomy for an atypical meningioma. The meningioma recurred once in the local site and was re-excised in 1997. In 2008, a screening chest X-ray detected two lung nodules in the right lung field. A computed tomographic scan demonstrated round masses with sharp borders, in the right S2 (2.2 cm in diameter) and S4 (1.1 cm in diameter) regions. A whole-body [(18)F]2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/CT examination revealed intense focal FDG uptake (maximum standard uptake value [SUV(max)] = 6.9) in the larger mass, and weak FDG uptake (SUV(max) = 2.3) in the smaller mass. A wedge resection of S2 and a middle lobectomy of the right lung were performed, and the final diagnosis was pulmonary metastases from an intracranial meningioma. The patient is presently doing well 20 months after the surgery without any signs of recurrence. Our case demonstrates that surgery should be considered when pulmonary metastases are deemed completely resectable by a preoperative radiological examination, and that a good clinical outcome can be achieved.

[Simultaneous surgery for left lung cancer and the aneurysm of an aberrant left subclavian artery in a patient with right aortic arch].

A 69-year-old man with right aortic arch was diagnosed as having left lung cancer (cT2aN1M0, cStage IIA) and an aneurysm of an aberrant left subclavian artery. The aneurysm measured 36 mm in diameter and was located 1 cm peripheral from the origin in the area known as "Kommerell's diverticulu Left carotid artery-to-left subclavian artery bypass graft was placed through a left supraclavicular incision prior to thoracotomy. This bypass graft effectively prevented neurological and ischemic complications of the brain and left upper extremity while we safely and successfully performed resection of the aneurysm along with radical surgery for left lung cancer through left thoracotomy. There have been only 10 case reports, including the present case, that have described surgical resection of lung cancer in a patient with right aortic arch. In addition, this is the 1st report to describe simultaneous surgery for both left lung cancer and an aneurysm of an aberrant left subclavian artery in a patient with right aortic arch.

Effects of Prophylaxis with Oral Supportive Care for Peri-implantitis in Patients Undergoing Malignancy Chemotherapy.

PURPOSE: Dental implants without proper maintenance may lead to serious consequences, such as peri-implantitis. Peri-implantitis in patients undergoing antitumour chemotherapy can negatively affect the prognosis of treatment. The purpose of this study was to examine the association between the onset of peri-implantitis and the effects of oral hygiene management in patients with dental implants undergoing antitumour chemotherapy. MATERIALS AND METHODS: Twenty-three patients (n = 23) with dental implants who received oral supportive care during malignancy chemotherapy were included. They were categorised into two groups based on the presence of peri-implantitis and were analysed for oral hygiene conditions, maintenance after implant insertion, and adverse effects such as febrile neutropenia. Statistical analysis was performed using the Fisher's exact test and the Mann-Whitney U-test, with p < 0.05 considered statistically significant. RESULTS: The average number of implants was higher in patients with peri-implantitis; these implants generally did not receive appropriate maintenance. There were statistically significantly fewer peri-implantitis sites in patients receiving continuous implant maintenance therapy than those who did not (p < 0.05). The severity of febrile neutropenia was reduced by dental interventions. CONCLUSION: Dental intervention before malignancy chemotherapy effectively prevented peri-implantitis and contributed to alleviating febrile neutropenia, even when it was initiated amidst chemotherapy. Dental intervention before chemotherapy seems essential in malignancy patients with dental implants.

Long-term survival in thymic carcinoma with postoperative pleural dissemination.

BACKGROUND: We report a patient with thymic squamous cell carcinoma who underwent multiple rounds of surgical resection and definitive radiotherapy for both primary tumor and postoperative recurrence. However, the patient remains well and healthy 18 years after initial diagnosis. Since long-term survival after postoperative recurrence of thymic carcinoma is extremely rare, we also present her immunohistochemical staining results, which suggested indolent disease. CASE PRESENTATION: A 42-year-old woman with thymic squamous cell carcinoma underwent en bloc resection of the tumor and thymus gland. Pleural dissemination was noted in the right thoracic cavity 3, 10, and 16 years postoperatively. Where possible, the nodules were resected surgically: during the postoperative 3rd and 16th years. Definitive radiotherapy was administered for all nodules that could not be excised during the postoperative 3rd and 10th years. Disease-free survival is 25 months. CONCLUSIONS: Local control of pleural dissemination may be beneficial in the treatment of postoperative recurrence of thymic carcinoma in limited cases of indolent disease.

A cross-population atlas of genetic associations for 220 human phenotypes.

Current genome-wide association studies do not yet capture sufficient diversity in populations and scope of phenotypes. To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n = 179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (ntotal = 628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping. Finally, we performed statistical decomposition of matrices of phenome-wide summary statistics, and identified latent genetic components, which pinpointed responsible variants and biological mechanisms underlying current disease classifications across populations. The decomposed components enabled genetically informed subtyping of similar diseases (for example, allergic diseases). Our study suggests a potential avenue for hypothesis-free re-investigation of human diseases through genetics.

Possibility of multivariate function composed of plasma amino acid profiles as a novel screening index for non-small cell lung cancer: a case control study.

BACKGROUND: The amino-acid balance in cancer patients often differs from that in healthy individuals, because of metabolic changes. This study investigated the use of plasma amino-acid profiles as a novel marker for screening non-small-cell lung cancer (NSCLC) patients. METHODS: The amino-acid concentrations in venous blood samples from pre-treatment NSCLC patients (n = 141), and age-matched, gender-matched, and smoking status-matched controls (n = 423), were measured using liquid chromatography and mass spectrometry. The resultant study data set was subjected to multiple logistic regression analysis to identify amino acids related with NSCLC and construct the criteria for discriminating NSCLC patients from controls. A test data set derived from 162 patients and 3,917 controls was used to validate the stability of the constructed criteria. RESULTS: The plasma amino-acid profiles significantly differed between the NSCLC patients and the controls. The obtained model (including alanine, valine, isoleucine, histidine, tryptophan and ornithine concentrations) performed well, with an area under the curve of the receiver-operator characteristic curve (ROC_AUC) of >0.8, and allowed NSCLC patients and controls to be discriminated regardless of disease stage or histological type. CONCLUSIONS: This study shows that plasma amino acid profiling will be a potential screening tool for NSCLC.