Radiofrequency ablation in patients with interstitial lung disease and lung neoplasm: a retrospective multicenter study.

PURPOSE: To retrospectively investigate the safety and efficacy of percutaneous radiofrequency ablation (RFA) by analyzing results in patients with lung neoplasm accompanied by interstitial lung disease (ILD) on computed tomography (CT) in a multicenter study. MATERIALS & METHODS: Patients with lung neoplasm accompanied by ILD who underwent RFA between April 2002 and October 2017 at seven institutions were investigated. Technical success rate, and local tumor progression (LTP) of ablated tumors were evaluated. Adverse events including acute exacerbation of ILD were also evaluated. Univariate analyses were performed to identify factors associated with acute exacerbation. RESULTS: Forty-nine patients with 64 lung neoplasm (mean diameter, 22.6 mm; range, 4-58 mm) treated in 66 sessions were included. Usual interstitial pneumonia (UIP) pattern on CT was identified in 23 patients (47%). All patients underwent successful RFA. Acute exacerbations were seen in 5 sessions (8%: 7% with UIP pattern, 8% without) in 5 patients, all occurring on or after 8 days (median, 12 days; range, 8-30 days). Three of those 5 patients died of acute exacerbation. Treatment resulted in mortality after 5% of sessions, representing 6% of patients. Pleural effusion and fever ≥38°C after RFA were identified by univariate analysis (p = 0.0012, p = 0.02, respectively) as significant risk factors for acute exacerbation. The cumulative LTP rate was 43% at 1 year. CONCLUSIONS: RFA appears feasible for patients with lung neoplasm complicated by ILD. Acute exacerbation occurred in 8% of patients with symptoms occurring more than 8 days post-ablation and was associated with a 45% mortality rate.

Modification of Visible-Light-Responsive Pb2Ti2O5.4F1.2 with Metal Oxide Cocatalysts to Improve Photocatalytic O2 Evolution toward Z-Scheme Overall Water Splitting.

The development of a highly active photocatalyst for visible-light water splitting requires a high-quality semiconductor material and a cocatalyst, which promote both the migration of photogenerated charge carriers and surface redox reactions. In this work, a cocatalyst was loaded onto an oxyfluoride photocatalyst, Pb2Ti2O5.4F1.2, to improve the water oxidation activity. Among the metal oxides examined as cocatalysts, RuO2 was found to be the most suitable, and the O2 evolution activity depended on the preparation conditions for Ru/Pb2Ti2O5.4F1.2. The highest activity was obtained with RuCl3-impregnated Pb2Ti2O5.4F1.2 heated under a flow of H2 at 523 K. The H2-treated Ru/Pb2Ti2O5.4F1.2 showed an O2 evolution rate an order of magnitude higher than those for the analogues without the H2 treatment (e. g., RuO2/Pb2Ti2O5.4F1.2). Physicochemical analyses by X-ray absorption fine-structure spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, and time-resolved microwave conductivity measurements indicated that the optimized photocatalyst contained partially reduced RuO2 species with a particle size of ~5 nm. These partially reduced species effectively trapped the photogenerated charge carriers and promoted the oxidation of water into O2. The optimized Ru/Pb2Ti2O5.4F1.2 could function as an O2-evolving photocatalyst in Z-scheme overall water splitting, in combination with an Ru-loaded, Rh-doped SrTiO3 photocatalyst.

Transarterial Embolization of Renal Arteriovenous Malformations: Treatment Outcomes According to Angiographic Classification.

PURPOSE: To assess the different adjunctive catheter techniques required to achieve complete occlusion of renal arteriovenous malformations (rAVMs) of different angioarchitectural types. MATERIALS AND METHODS: Overall, data on 18 patients with rAVM (Type 1, n = 7; Type 2, n = 2; Type 3, n = 9; mean age, 53.8 years) who underwent 25 procedures between 2011 and 2022 were reviewed. The clinical presentations, endovascular techniques, arteriovenous malformation (AVM) occlusion rate, adverse events (including the incidence of renal infarction), and clinical symptoms and outcomes (including recurrence/increase of AVM) were analyzed according to the Cho-Do angioarchitectural classification. Posttreatment renal infarction was classified as no infarction, small infarction (<12.5%), medium infarction (12.5%-25%), and large infarction (>25%) using contrast-enhanced computed tomography or magnetic resonance imaging. RESULTS: Hematuria and heart failure were presenting symptoms in 10 and 2 patients, respectively. The embolic materials used were as follows: Type 1 rAVM, coils alone or with n-butyl-2-cyanoacrylate (nBCA); Type 2 rAVM, nBCA alone or with coils; and Type 3 rAVMs, nBCA alone. Fourteen patients underwent adjunctive catheter techniques, including flow control with a balloon catheter and multiple microcatheter placement, alone or in combination. Immediate postprocedural angiography revealed complete occlusion in 15 patients (83%) and marked regression of rAVM in 3 (17%). Small asymptomatic renal infarctions were observed in 6 patients with Type 3 rAVMs without any decrease in renal function. No major adverse events were observed. All symptomatic patients experienced symptom resolution. Recurrence/increase of rAVM was not observed during the mean 32-month follow-up period (range, 2-120 months). CONCLUSIONS: Transarterial embolization using adjunctive catheter techniques according to angioarchitectural types can be an effective treatment for rAVMs.

Hepatic venous outflow obstruction after adult living donor liver transplantation.

Hepatic venous outflow obstruction (HVOO) is a rare but critical vascular complication after adult living donor liver transplantation. We categorized HVOOs according to their morphology (anastomotic stenosis, kinking, and intrahepatic stenosis) and onset (early-onset < 3 mo vs. late-onset ≥ 3 mo). Overall, 16/324 (4.9%) patients developed HVOO between 2000 and 2020. Fifteen patients underwent interventional radiology. Of the 16 hepatic venous anastomoses within these 15 patients, 12 were anastomotic stenosis, 2 were kinking, and 2 were intrahepatic stenoses. All of the kinking and intrahepatic stenoses required stent placement, but most of the anastomotic stenoses (11/12, 92%) were successfully managed with balloon angioplasty, which avoided stent placement. Graft survival tended to be worse for patients with late-onset HVOO than early-onset HVOO (40% vs. 69.3% at 5 y, p = 0.162) despite successful interventional radiology. In conclusion, repeat balloon angioplasty can be considered for simple anastomotic stenosis, but stent placement is recommended for kinking or intrahepatic stenosis. Close follow-up is recommended in patients with late-onset HVOO even after successful treatment.

Prompt Reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1 and a Relatively Low Basal Ratio of Ferritin/CRP Is Possibly Associated With the Efficacy of Tocilizumab Monotherapy in Severely to Critically Ill Patients With COVID-19.

Background and Aim: Tocilizumab, a humanized anti-IL-6 receptor antibody, has been used to treat severely to critically ill patients with COVID-19. A living systematic review with meta-analysis of recent RCTs indicates that the combination therapy of corticosteroids and tocilizumab produce better outcomes, while previous observational studies suggest that tocilizumab monotherapy is beneficial for substantial numbers of patients. However, what patients could respond to tocilizumab monotherapy remained unknown. Methods: In this retrospective study we evaluated the effects of tocilizumab monotherapy on the clinical characteristics, serum biomediator levels, viral elimination, and specific IgG antibody induction in 13 severely to critically ill patients and compared with those of dexamethasone monotherapy and dexamethasone plus tocilizumab. Results: A single tocilizumab administration led to a rapid improvement in clinical characteristics, inflammatory findings, and oxygen supply in 7 of 11 patients with severe COVID-19, and could recover from mechanical ventilation management (MVM) in 2 patients with critically ill COVID-19. Four patients exhibited rapidly worsening even after tocilizumab administration and required MVM and additional methylprednisolone treatment. Tocilizumab did not delay viral elimination or inhibit IgG production specific for the virus, whereas dexamethasone inhibited IgG induction. A multiplex cytokine array system revealed a significant increase in the serum expression of 54 out of 80 biomediators in patients with COVID-19 compared with that in healthy controls. Compared with those who promptly recovered in response to tocilizumab, patients requiring MVM showed a significantly higher ratio of basal level of ferritin/CRP and a persistent increase in the levels of CRP and specific cytokines and chemokines including IL-6, IFN-γ, IP-10, and MCP-1. The basal high ratio of ferritin/CRP was also associated with clinical deterioration even in patients treated with dexamethasone and tocilizumab. Conclusion: Tocilizumab as monotherapy has substantial beneficial effects in some patients with severe COVID-19, who showed a relatively low level of the ratio of ferritin/CRP and prompt reduction in CRP, IL-6, IFN-γ, IP-10, and MCP-1. The high ratio of ferritin/CRP is associated with rapid worsening of pneumonia. Further evaluation is warranted to clarify whether tocilizumab monotherapy or its combination with corticosteroid is preferred for severely to critically ill patients with COVID-19.

Novel Approach via the Round Ligament in Portal Vein Embolization.

BACKGROUND: The objective of this study was to describe the detailed technique and clinical outcomes of portal vein embolization via the round ligament (RL-PVE) prior to major hepatectomy. METHODS: Between January 2010 and March 2020, a total of 50 portal vein embolization (PVE) procedures were performed in 50 patients. Of them, seven patients who underwent RL-PVE were enrolled in this study. Percutaneous transhepatic portal vein embolization (PTPE) was not indicated due to the following reasons: bile duct dilation (n = 4), difficulty in visualizing the portal vein on ultrasonography because of severe fatty liver (n = 1), large tumor size (n = 1), and combined surgery with staging laparoscopy (n = 1). The following were reasons for avoiding trans-ileocecal PVE: past laparotomy (n = 5), difficulty in accessing the portal vein due to a large tumor (n = 1), and purpose of preventing small intestinal adhesions before hepatopancreatoduodenectomy (n = 1). The percentage of functional hepatic remnant rates was calculated before and after RL-PVE. RESULTS: Technical success was achieved in all cases. Five patients underwent embolization of the right portal vein, while two underwent embolization of the left portal vein. The median operative time and blood loss during RL-PVE were 181 min and 33 g, respectively. Morbidity and mortality related to RL-PVE were not observed. The median functional hepatic remnant rate before and after PVE was 55.6% and 63.2%, respectively. Liver functions including Child-Pugh classification were equivalent before and after RL-PVE. CONCLUSIONS: The RL-PVE technique may be useful in elective cases for which it is difficult to safely perform PTPE or trans-ileocecal approaches.

Development of an efficient one-step real-time reverse transcription polymerase chain reaction method for severe acute respiratory syndrome-coronavirus-2 detection.

The general methods to detect the RNA of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in clinical diagnostic testing involve reverse transcriptases and thermostable DNA polymerases. In this study, we compared the detection of SARS-CoV-2 by a one-step real-time RT-PCR method using a heat-resistant reverse transcriptase variant MM4 from Moloney murine leukemia virus, two thermostable DNA polymerase variants with reverse transcriptase activity from Thermotoga petrophila K4 and Thermococcus kodakarensis KOD1, or a wild-type DNA polymerase from Thermus thermophilus M1. The highest performance was achieved by combining MM4 with the thermostable DNA polymerase from T. thermophilus M1. These enzymes efficiently amplified specific RNA using uracil-DNA glycosylase (UNG) to remove contamination and human RNase P RNA amplification as an internal control. The standard curve was obtained from 5 to 105 copies of synthetic RNA. The one-step real-time RT-PCR method's sensitivity and specificity were 99.44% and 100%, respectively (n = 213), compared to those of a commercially available diagnostic kit. Therefore, our method will be useful for the accurate detection and quantification of SARS-CoV-2.

Scoring system for identifying Japanese patients with COVID-19 at risk of requiring oxygen supply: A retrospective single-center study.

INTRODUCTION: Japan is facing the threat of medical system collapse due to the rapid spread of coronavirus disease 2019 (COVID-19). The present scoring system may help assess disease severity and oxygen supply requirements in COVID-19 patients. METHODS: Data on patient characteristics at baseline and throughout hospitalization for COVID-19 were extracted from medical records. Disease severity was dichotomized into two categories without or with oxygen supply as asymptomatic, mild, and moderate illness (AMMI), and severe and critical illness (CSI). The AMMI and CSI groups were compared. Predictors of disease severity, previously identified in the outpatient setting, were included in multivariable logistic regression analysis; the obtained coefficients were converted to integers and assigned a score. RESULTS: A total of 206 patients diagnosed with COVID-19 were included in this study. Correlation between COVID-19 severity and medical information was examined by comparing AMMI and CSI. Age, hemodialysis, and C-reactive protein (CRP) levels were candidate predictors of the need for oxygen supply in patients with COVID-19. Coefficients associated with age, hemodialysis, and CRP were as follows: 1 × age (in years, coded as 0 for values of <50, and as 1 for values of ≥50) + 1 × hemodialysis (coded as 0 for "no", and as 1 for "yes") + 1 × CRP (in mg/dL, coded as 0 for values of <1.0, and as 1 for values of ≥1.0). Patients with scores of ≥2 points required oxygen supply (sensitivity, 68.4%; specificity, 79.0%) CONCLUSION: The present model can help predict disease severity and oxygen requirements in COVID-19 patients in Japan.

Clinical COVID-19 diagnostic methods: Comparison of reverse transcription loop-mediated isothermal amplification (RT-LAMP) and quantitative RT-PCR (qRT-PCR).

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a major public health concern. Accurate and rapid diagnosis of COVID-19 is critical for disease control. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a nucleic acid amplification assay similar to reverse transcription-polymerase chain reaction (RT-PCR), the former being a simple, low cost, and rapid method. OBJECTIVES: This study aimed to compare the RT-LAMP assay with RT-PCR using the Loopamp™ SARS-CoV-2 Detection Kit. STUDY DESIGN: One hundred and fifty-one nasopharyngeal swab and 88 sputum samples obtained from individuals with suspected or confirmed COVID-19 were examined. RESULTS: RT-LAMP had high specificity (98.5 % (95 % CI: 96.9-100 %)), sensitivity (87.0 % (95 % CI: 82.8-91.3 %)), positive predictive value (97.9 % (95 % CI: 96.1-99.7 %)), negative predictive value (90.2 % (95 % CI: 86.4-94.0 %)), and concordance rate (93.3 % (95 % CI: 90.1-96.5 %)). Nasopharyngeal and sputum samples positive in RT-LAMP contained as few as 10.2 and 23.4 copies per 10 µL, respectively. RT-LAMP showed similar performance to RT-PCR for samples with cycle threshold value below 36. CONCLUSIONS: These results indicate that RT-LAMP is a highly reliable and at least equivalent to RT-PCR in utility, and potentially applicable in settings that are more diverse as a point-of-care tool.

Transbronchial Cryobiopsy for Miliary Tuberculosis Mimicking Hypersensitivity Pneumonitis.

Miliary tuberculosis is a potentially lethal type of tuberculosis that results from the hematogenous dissemination of Mycobacterium tuberculosis bacilli. We herein describe the case of a 34-year-old man that presented with a one-month history of cough and fever, while his sputum smear results were negative. Chest computed tomography revealed bilateral centrilobular ground-glass opacification (GGO), suggestive of hypersensitivity pneumonitis; thus, bronchoscopy was performed. Cryobiopsy specimens revealed necrotic granulomas. A re-examination of sputum after bronchoscopy identified Mycobacterium tuberculosis, and miliary tuberculosis was diagnosed. A cryobiopsy might be useful for diagnosing miliary tuberculosis pathologically, particularly when miliary nodules may be masked by GGO.

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study.

INTRODUCTION: The severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020. METHODS: All patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients' records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software. RESULTS: Data from 61 patients (16 Pt-CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt-CSI were significantly older and had hypertension or diabetes than Pt-MMI (P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt-CSI than in Pt-MMI (P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt-CSI than in Pt-MMI (P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt-CSI than in Pt-MMI (P = 0.013). Among the 16 Pt-CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died. CONCLUSIONS: The illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.

Significance of Pre-treatment Interferon-gamma Release in Patients With Non-small-cell Lung Cancer Receiving Immune Checkpoint Inhibitors.

BACKGROUND/AIM: We retrospectively investigated the significance of pre-treatment interferon-gamma release (IGR) as a biomarker for predicting the efficacy of immune checkpoint inhibitor treatment (ICI-tx). PATIENTS AND METHODS: This study included non-small-cell lung cancer patients who received ICI-tx between January 1, 2016 and April 30, 2019. IGR was measured using the positive control of an enzyme-linked immunosorbent assay. We defined the pre-treatment cut-off level of IGR as 10 IU/ml. RESULTS: Fifty-four patients were divided into two groups; those with an IGR ≤10 IU/ml (lower group: LG) (n=15) and those with >10 IU/ml (higher group: HG) (n=39). The time to treatment failure (TTF) in the HG was significantly longer than that in the LG. In multivariate analyses, C-reactive protein and IGR levels were significant risk factors for TTF. CONCLUSION: Pre-treatment IGR level of >10 IU/ml is recommended to identify those patients who will respond favourably to ICI-tx.

Significance of Quantitative Interferon-gamma Levels in Non-small-cell Lung Cancer Patients' Response to Immune Checkpoint Inhibitors.

BACKGROUND/AIM: We aimed to study the association between the quantitative interferon-gamma (IFN-γ) levels and clinical outcomes in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: Sample collection for IFN-γ release assay (IGRA) was performed within 14 days before treatment (T1), on day 22±7 (T3), and on day 43±7 (T4). The stored specimens over 10 IU/ml in IGRA were re-examined using the dilution method (with saline as the dilution medium). The patients were classified into Lower and Higher groups by 7.06 IU/ml as a cut-off of IFN-γ levels at T1. RESULTS: Median progression-free survival in the Higher group was significantly longer than that in the Lower group. IFN-γ levels in the non-progression disease group were significantly higher than those in the progression disease group. IFN-γ levels at T1 in patients with immune-related adverse events were significantly lower compared to those at T3. CONCLUSION: IFN-γ could be a biomarker for NSCLC patients receiving ICIs.

The Levels of Interferon-gamma Release as a Biomarker for Non-small-cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

BACKGROUND/AIM: The present study aimed to prospectively examine the usefulness of interferon-gamma (IFN-γ) release (IGR) as a biomarker in non-small-cell lung cancer patients receiving immune checkpoint inhibitor treatment (ICI-Tx). PATIENTS AND METHODS: IGR was measured using enzyme-linked immunosorbent assay at four time points: within 14 days before ICI-Tx (T1), and 8±3 (T2), 22±7 (T3), and 43±7 (T4) days after ICI-Tx. RESULTS: Twenty-nine patients were divided into three groups based on IFN-γ levels in the IGR-positive control: Group-1 (n=8) with <10 IU/ml at T1, Group-2 (n=12) with a decrease in IFN-γ levels to <10 IU/ml at T3 and/or T4, and Group-3 (n=9) without changes in IFN-γ levels. Early progression and ICI-induced interstitial pneumonitis were frequently observed in Group-1 and Group-2, respectively. Group-3 exhibited more treatment cycles than the other groups. All three groups showed clear differences in clinical outcomes. CONCLUSION: IFN-γ levels could be a biomarker for ICI-Tx.

Efficacy of repeated balloon venoplasty for treatment of hepatic venous outflow obstruction after pediatric living-donor liver transplantation: A single-institution experience.

HVOO is a rare complication after LT and an important cause of graft failure. Balloon venoplasty is the first-line treatment for HVOO, but the effect of repeated balloon venoplasty and stent placement for HVOO recurrence after pediatric LDLT remains unclear. Between 1998 and 2016, 147 pediatric patients underwent LDLT in our institution. Among them, the incidence of HVOO and the therapeutic strategy were retrospectively reviewed. Ten patients were diagnosed with HVOO. All the patients underwent LLS grafts. Median age at the initial endovascular intervention was 2.7 years (range, 5 months-8 years). The median interval between the LDLT and the initial interventional radiology was 2.7 months (range, 29 days-35.7 months). Four patients experienced no recurrence after a single balloon venoplasty; 6 underwent balloon venoplasty more than 3 times because of HVOO recurrence; and 2 underwent stent placement due to the failure of repeated balloon venoplasty. All patients are alive with no symptoms of HVOO. The HVOO recurrence-free period after the last intervention ranged from 20 days to 15.5 years (median, 8.9 years). Repeated balloon venoplasty may prevent unnecessary stent placement to treat recurrent HVOO after pediatric LDLT.

Contrast Enhancement Boost Technique at Aortic Computed Tomography Angiography: Added Value for the Evaluation of Type II Endoleaks After Endovascular Aortic Aneurysm Repair.

RATIONALE AND OBJECTIVES: Delayed-phase acquisition of the computed tomography (CT) angiography is important for the evaluation of type II endoleaks after endovascular aortic aneurysm repair because the endoleak cavity area is associated with aneurysm sac expansion. Contrast enhancement boost (CE-boost) is a postprocessing technique for increasing the degree of contrast enhancement on contrast-enhanced CT. We aimed to investigate the usefulness of the CE-boost technique for the visualization of type II endoleaks. MATERIALS AND METHODS: This retrospective study included 28 patients with type II endoleaks after endovascular aortic aneurysm repair who underwent triphasic contrast-enhanced CT. Objective (CT number, signal-to-noise ratio, and contrast-to-noise ratio) and subjective quality analyses using a four-point scale (1, poor; 4, excellent) were performed for the conventional early- and delayed-phase images as well as CE-boost delayed-phase images. RESULTS: The CE-boost delayed-phase images yielded a significantly higher CT number (134.5 ± 41.7 HU), signal-to-noise ratio (23.4 ± 10.5), and contrast-to-noise ratio (15.3 ± 8.4) and showed a significantly larger endoleak area (145.0 ± 134.8 mm2) than did the conventional early-phase (95.6 ± 53.2 HU, 7.3 ± 4.7, 4.0 ± 4.2, and 56.2 ± 99.3 mm2, respectively) and delayed-phase (110.5 ± 33.3 HU, 8.2 ± 2.7, 4.9 ± 2.0, and 124.8 ± 131.9 mm2, respectively) images (p < 0.01). The endoleak visibility score was highest for the CE-boost delayed-phase images (2.0 ± 1.0, 3.0 ± 0.6, and 3.4 ± 0.7 for conventional early-phase, delayed-phase, and delayed-phase CE-boost images, respectively; p < 0.001). CONCLUSION: The CE-boost technique facilitates clear visualization of type II endoleak cavities.

Paradoxical response in a patient with non-small cell lung cancer who received nivolumab followed by anti-Mycobacterium tuberculosis agents.

Anti-programmed cell death-1 (PD-1) agents enhance the antitumor immunoresponse. A number of reports have indicated that patients with malignancies who receive anti-PD-1 agents are at risk for tuberculosis (TB) infection. In this report, we present a patient with non-small cell lung cancer who developed pulmonary tuberculosis while receiving the anti-PD-1 agent nivolumab, and who subsequently demonstrated a paradoxical response (PR) 10 days after initiation of anti-MTB treatment. We suggest that anti-PD-1 agents not only induce the development of pulmonary TB, but also development of PR after anti-MTB treatment, through upregulation of the immune response. Furthermore, based on their radiological and immunological similarity, we speculate that the schema of development of PR closely resembles that of pseudoprogression in non-small cell lung cancer patients after anti-PD-1 treatment.

Efficacy and safety of concurrent anti-Cancer and anti-tuberculosis chemotherapy in Cancer patients with active Mycobacterium tuberculosis: a retrospective study.

BACKGROUND: In our previous study, colorectal cancer (CRC) patients with active Mycobacterium tuberculosis (MTB) tolerated concurrent anti-cancer chemotherapy (anti-CCT) and anti-MTB chemotherapy. In this study, we retrospectively confirmed the efficacy and safety of concurrent chemotherapy in a greater number of patients with different types of malignancies. METHODS: We enrolled 30 patients who were treated concurrently with anti-CCT and anti-MTB regimens between January 2006 and February 2016. Cancer and MTB treatments were administered according to the approved guidelines. RESULTS: Patient demographics included: men/woman: 24/6; median age: 66.5 years; Eastern Cooperative Oncology Group performance status 0-1/2/3-4: 24/4/2; Stage IIB-IIIC/IV/recurrence: 6/22/2; lung cancer (LC)/CRC/other: 15/10/5; and MTB diagnosis (before or during anti-CCT): 20/10 (LC: 8/7; CRC: 8/2; other: 4/1). For anti-CCT, 23 patients received two cytotoxic agents with or without targeted agents and 7 patients received a single cytotoxic or targeted agent. The overall response rate was 36.7%. Regarding anti-MTB chemotherapy, 22 patients received a daily drug combination containing isoniazid, rifampicin, and ethambutol, plus pyrazinamide in 15 of the 22 patients, followed by daily isoniazid and rifampicin; the remaining 8 patients received other combinations. Hematological adverse events of Grade ≥ 3 were observed in 19 (67.9%) of 28 patients; laboratory data were lost for the remaining 2. Grade 3 lymphopenia and higher were significantly more frequent in LC compared to other malignancies (P < 0.005). Non-hematological adverse events of Grade ≥ 3 were observed in 5 (16.7%) of 30 patients. One CRC patient experienced Grade 3 hemoptysis and another 2 experienced Grade 3 anaphylaxis. One patient with cholangiocellular carcinoma and gastric cancer experienced Grade 3 pseudomembranous colitis as a result of a Clostridium difficile infection. One patient (3.3%) died of pemetrexed-induced pneumonitis. The success of the anti-MTB chemotherapy was 70.0%. There were no MTB-related treatment failures. The median overall survival (months, 95.0% confidence interval) was 10.5 (8.7-36.7), 8.7 (4.7-10.0), 36.7 (minimum 2.2), and 14.4 (minimum 9.6) for all patients combined, LC, CRC, and Other malignancies, respectively. LC patients experienced delayed MTB diagnosis and shorter overall survival. CONCLUSIONS: Concurrent chemotherapy is effective and safe for treating cancer patients with active MTB.