Detection of actionable mutations in cytological specimens obtained by endoscopic ultrasound-guided fine needle aspiration with rapid onsite evaluation in pancreatic cancer.

BACKGROUND: It is not clear whether archived cytological specimens (ACSs) obtained with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with rapid onsite evaluation (ROSE) can be used for genomic profiling of tumors. We used ACSs to perform genomic analysis of specimens to identify oncogenic and druggable mutations. METHODS: A panel of 60 significantly mutated genes specific to pancreatobiliary cancer was created and used for genomic analysis of 113 specimens of 44 formalin-fixed paraffin-embedded (FFPE) tissues and 69 ACSs obtained by EUS-FNA with ROSE were included. The quantity and quality of DNA extracted from FFPE tissues and ACSs were compared. We also compared DNA from spray and touch ACSs. Next, genomic profiles were compared. We also evaluated detection of target gene mutations in each specimen. RESULTS: The amount of DNA in FFPE tissues was greater than in ACSs (P = 0.014), but the quality of DNA was comparable (P = 0.378). There was no quantitative or qualitative difference between spray and touch ACSs (P = 0.154 and P = 0.734, respectively). Oncogenic mutations were shared at 82 % in FFPE tissues and ACSs and 82 % in spray and touch ACSs. The sensitivity of genomic analysis in ACSs was 97 % (67 of 69), which was comparable to that of cytology (62 of 69, 90 %; P = 0.165), and was significantly higher than that of histology (32/44, 73 %; P < 0.001). Drug-matched mutations were identified in five of the 44 lesions (11 %). CONCLUSION: Genomic analysis of ACSs is useful in the prognosis of pancreatic cancer because detection of driver mutations is similar to detection in FFPE tissues.

Rapidly declining trend of signet ring cell cancer of the stomach may parallel the infection rate of Helicobacter pylori.

BACKGROUND: Studies indicate that gastric cancer (GC) incidence has decreased, whereas signet ring cell carcinoma (SRC) incidence has increased. However, recent trends in GC incidence are unclear. We used our hospital cancer registry to evaluate the changes in the incidence of GC, SRC, and non-SRC (NSRC) over time in comparison to changes in the H. pylori infection rates over time. METHODS: We identified 2532 patients with GC enrolled in our registry between January 2007 and December 2018 and statistically analyzed SRC and NSRC incidence. The H. pylori infection rate in patients with SRC was determined by serum anti-H. pylori antibody testing, urea breath test, biopsy specimen culture, and immunohistochemical analysis (IHC) of gastric tissue. Additionally, genomic detection of H. pylori was performed in SRCs by extracting DNA from formalin-fixed paraffin-embedded gastric tissue and targeting 16S ribosomal RNA of H. pylori. RESULTS: Overall, 211 patients had SRC (8.3%). Compared with patients with NSRC, those with SRC were younger (P <  0.001) and more likely to be female (P <  0.001). Time series analysis using an autoregressive integrated moving average model revealed a significant decrease in SRC (P <  0.001) incidence; NSRC incidence showed no decline. There was no difference in H. pylori infection prevalence between the SRC and NSRC groups. IHC and genomic methods detected H. pylori in 30 of 37 (81.1%) SRCs. CONCLUSIONS: Reduction in H. pylori infection prevalence may be associated with the decrease in the incidence of SRC, which was higher than that of NSRC.

Robotic Renal Autotransplantation: First Case Outside of North America.

A 38-year-old woman with a 2.7-cm left ureteral stenosis requiring chronic ureteral stent exchange elected to undergo robotic renal autotransplantation. Left ureteropelvic junction obstruction (UPJO) was also suspected. Robotic donor nephrectomy contributed to the fine dissection for desmoplastic changes. The kidney was removed through a Gelport and examined on ice. UPJO was not seen. An end-to-side robotic anastomosis was created between the renal and external iliac vessels. The console time was 507 min, and the warm ischemia time was 4 min 5 sec. She became stent-free. Robotic renal autotransplantation is a new, minimally invasive approach to renal preservation.

Bidirectional role of IL-6 signal in pathogenesis of lung fibrosis.

BACKGROUND: Various signals are known to participate in the pathogenesis of lung fibrosis. Our aim was to determine which signal is predominantly mobilized in the early inflammatory phase and thereafter modulates the development of lung fibrosis. METHODS: Mice received a single dose of 3 mg/kg body weight of bleomycin (BLM) and were sacrificed at designated days post-instillation (dpi). Lung homogenates and sections from mice in the early inflammatory phase were subjected to phospho-protein array analysis and immunofluorescence studies, respectively. Bronchoalveolar lavage fluid (BALF) from mice was subjected to an enzyme-linked immunosorbent assay (EIA) for interleukin (IL)-6 and evaluation of infiltrated cell populations. The effects of endogenous and exogenous IL-6 on the BLM-induced apoptotic signal in A549 cells and type 2 pneumocytes were elucidated. In addition, the effect of IL-6-neutralizing antibody on BLM-induced lung injury was evaluated. RESULTS: Phospho-protein array revealed that BLM induced phosphorylation of molecules downstream of the IL-6 receptor such as Stat3 and Akt in the lung at 3 dpi. At 3 dpi, immunofluorescence studies showed that signals of phospho-Stat3 and -Akt were localized in type 2 pneumocytes, and that BLM-induced IL-6-like immunoreactivity was predominantly observed in type 2 pneumocytes. Activation of caspases in BLM-treated A549 cells and type 2 pneumocytes was augmented by application of IL-6-neutralizing antibody, a PI3K inhibitor or a Stat3 inhibitor. EIA revealed that BLM-induced IL-6 in BALF was biphasic, with the first increase from 0.5 to 3 dpi followed by the second increase from 8 to 10 dpi. Blockade of the first increase of IL-6 by IL-6-neutralizing antibody enhanced apoptosis of type 2 pneumocytes and neutrophilic infiltration and markedly accelerated fibrosis in the lung. In contrast, blockade of the second increase of IL-6 by IL-6-neutralizing antibody ameliorated lung fibrosis. CONCLUSIONS: The present study demonstrated that IL-6 could play a bidirectional role in the pathogenesis of lung fibrosis. In particular, upregulation of IL-6 at the early inflammatory stage of BLM-injured lung has antifibrotic activity through regulating the cell fate of type 2 pneumocytes in an autocrine/paracrine manner.

p38 Mitogen-activated protein kinase accelerates emphysema in mouse model of chronic obstructive pulmonary disease.

CONTEXT: There are few short-term mouse models of chronic obstructive pulmonary disease (COPD) mimicking the human disease. In addition, p38 is recently recognized as a target for the treatment of COPD. However, the precise mechanism how p38 contributes to the pathogenesis of COPD is still unknown. OBJECTIVE: We attempted to create a new mouse model for COPD by intra-tracheal administration of a mixture of lipopolysaccharide (LPS) and cigarette smoke solution (CSS), and investigated the importance of the p38 mitogen-activated protein kinase (p38) pathway in the pathogenesis of COPD. METHODS: Mice were administered LPS + CSS once a day on days 0-4 and 7-11. Thereafter, CSS alone was administered to mice once a day on days 14-18. On day 28, histopathological changes of the lung were evaluated, and bronchoalveolar lavage fluid (BALF) was subjected to western blot array for cytokines. Transgenic (TG) mice expressing a constitutive-active form of MKK6, a p38-specific activator in the lung, were subjected to our experimental protocol of COPD model. RESULTS: LPS + CSS administration induced enlargement of alveolar air spaces and destruction of lung parenchyma. BALF analyses of the LPS + CSS group revealed an increase in expression levels of several cytokines involved in the pathogenesis of human COPD. These results suggest that our experimental protocol can induce COPD in mice. Likewise, histopathological findings of the lung and induction of cytokines in BALF from MKK6 c.a.-TG mice were more marked than those in WT mice. CONCLUSION: In a new experimental COPD mouse model, p38 accelerates the development of emphysema.

[IgG4-related kidney disease: a long-term follow up case of pseudotumor of the renal pelvis].

A 69-year-old man had undergone left ureteronephrectomy because of a left renal pelvic tumor, however the pathological diagnosis was inflammatory pseudotumor. About 1 year later, computed tomography showed a mass at the right kidney near the hilar. Ureterorenoscopy and urine cytology were performed, and their results showed no evidence of malignancy. He had been followed closely without therapy. The mass increased in size during follow-up, and we reviewed the surgical specimen of the left ureteronephrectomy. Immunohistochemical studies revealed diffuse infiltration by IgG4 positive plasma cell. His serum IgG4 was high. We diagnosed him as IgG4-related kidney disease. In response to treatment with corticosteroid, the size of the tumor and serum IgG4 levels decreased. Most reported cases of IgG4-related disease involving kidney have a history of prior pancreatic involvement. We report a rare long term follow-up case of IgG4-related kidney disease without pancreatic involvement.

Development of a molecular barcode detection system for pancreaticobiliary malignancies and comparison with next-generation sequencing.

BACKGROUND: Obtaining sufficient tumor tissue for genomic profiling is challenging in pancreaticobiliary cancer (PBCA). We determined the utility of molecular barcoding (MB) of liquid biopsies (bile, duodenal fluid, and plasma) for highly sensitive genomic diagnosis and detection of druggable mutations for PBCA. METHODS: Two in-house panels of 60 genes (non-MB panel) and 21 genes using MB (MB panel) were used for the genomic analysis of 112 DNA samples from 20 PBCA patients. We measured the yield of DNA and compared the genomic profiles of liquid samples obtained using the non-MB panel and the MB panel. The utility of the panels in detecting druggable mutations was investigated. RESULTS: A significantly greater amount of DNA was obtained from bile supernatants and precipitates compared to tumor samples (P < 0.001 and P = 0.001, respectively). The number of mutations per patient was significantly higher using the MB panel than using the non-MB panel (2.8 vs. 1.3, P = 0.002). Tumor-derived mutations were detected more frequently using the MB panel than the non-MB panel (P = 0.023). Five drug-matched mutations were detected in liquid samples. CONCLUSIONS: Liquid biopsy with MB may have utility in providing genomic information for the prognosis of patients with PBCA.

Liquid biopsy of wash samples obtained via endoscopic ultrasound-guided fine-needle biopsy: Comparison with liquid biopsy of plasma in pancreatic cancer.

OBJECTIVES: Pancreatic cancer (PC) has a poor prognosis and limited treatment options. Liquid biopsy, which analyzes circulating tumor DNA (ctDNA) in blood, holds promise for precision medicine; however, low ctDNA detection rates pose challenges. This study aimed to investigate the utility of wash samples obtained via endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) as a liquid biopsy for PC. METHODS: A total of 166 samples (42 formalin-fixed paraffin-embedded [FFPE] tissues, 80 wash samples, and 44 plasma samples) were collected from 48 patients with PC for genomic analysis. DNA was extracted and quantified, and 60 significantly mutated genes were sequenced. The genomic profiles of FFPE tissues, wash samples, and plasma samples were compared. Finally, the ability to detect druggable mutations in 80 wash samples and 44 plasma samples was investigated. RESULTS: The amount of DNA was significantly lower in plasma samples than in wash samples. Genomic analysis revealed a higher detection rate of oncogenic mutations in FFPE tissues (98%) and wash samples (96%) than in plasma samples (18%) and a comparable detection rate in FFPE tissues and wash samples. Tumor-derived oncogenic mutations were detected more frequently in wash samples than in plasma samples. Furthermore, the oncogenic mutations detection rate remained high in wash samples at all PC stages but low in plasma samples even at advanced PC stages. Using wash samples was more sensitive than plasma samples for identifying oncogenic and druggable mutations. CONCLUSIONS: The wash sample obtained via EUS-FNB is an ideal specimen for use as a liquid biopsy for PC.

A case of pulmonary tuberculosis that developed during nivolumab and ipilimumab treatment for pulmonary adenocarcinoma that recurred two months after completion of anti-tuberculous treatment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become key agents in the treatment of non-small cell lung cancer worldwide. However, immune-related adverse events (irAEs) must be addressed to maximize the efficacy of ICIs. Mycobacterium tuberculosis (Mtb) infection is considered as a type of irAE associated with ICIs, but the underlying mechanism is not completely understood. Here, we present a case of pulmonary tuberculosis (TB) that developed during administration of nivolumab and ipilimumab for pulmonary adenocarcinoma that recurred just 2 months after completion of anti-TB treatment. CASE DESCRIPTION: A 67-year-old man with lung adenocarcinoma was referred to our hospital for chemotherapy. He was a former smoker and had been diagnosed with stage IVA (cT4N1M1a) lung adenocarcinoma. Interferon-gamma release assay (IGRA) yielded positive results at the start of treatment. One month after initiating treatment with nivolumab and ipilimumab, he presented with productive cough and Mtb complex was cultured from sputum samples. Two months after completing anti-TB treatment, recurrence of TB was observed. The series of strains were found to be identical. CONCLUSIONS: This represents the first report of pulmonary TB that developed during nivolumab and ipilimumab treatment, and recurred 2 months after completing anti-TB treatment. Physicians should be mindful of the potential for TB recurrence following the use of ICIs, particularly in patients showing positive results from IGRA.

Comprehensive identification of terpene synthase genes and organ-dependent accumulation of terpenoid volatiles in a traditional medicinal plant Angelica archangelica L.

Angelica archangelica L. is a traditional medicinal plant of Nordic origin that produces an unusual amount and variety of terpenoids. The unique terpenoid composition of A. archangelica likely arises from the involvement of terpene synthases (TPSs) with different specificities, none of which has been identified. As the first step in identifying TPSs responsible for terpenoid chemodiversity in A. archangelica, we produced a transcriptome catalogue using the mRNAs extracted from the leaves, tap roots, and dry seeds of the plant; 11 putative TPS genes were identified (AaTPS1-AaTPS11). Phylogenetic analysis predicted that AaTPS1-AaTPS5, AaTPS6-AaTPS10, and AaTPS11 belong to the monoterpene synthase (monoTPS), sesquiterpene synthase (sesquiTPS), and diterpene synthase clusters, respectively. We then performed in vivo enzyme assays of the AaTPSs using recombinant Escherichia coli systems to examine their enzymatic activities and specificities. Nine recombinant enzymes (AaTPS2-AaTPS10) displayed TPS activities with specificities consistent with their phylogenetics; however, AaTPS5 exhibited a strong sesquiTPS activity along with a weak monoTPS activity. We also analyzed terpenoid volatiles in the flowers, immature and mature seeds, leaves, and tap roots of A. archangelica using gas chromatography-mass spectrometry; 14 monoterpenoids and 13 sesquiterpenoids were identified. The mature seeds accumulated the highest levels of monoterpenoids, with ß-phellandrene being the most prominent. α-Pinene and ß-myrcene were abundant in all organs examined. The in vivo assay results suggest that the AaTPSs functionally identified in this study are at least partly involved in the chemodiversity of terpenoid volatiles in A. archangelica.

[A case of small-cell lung carcinoma accompanied by the syndrome of inappropriate secretion of antidiuretic hormone and Lambert-Eaton myasthenic syndrome].

Although the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and Lambert-Eaton myasthenic syndrome (LEMS) are often individually accompanied by small-cell lung carcinoma, simultaneous occurrence of the 2 syndromes is rare. A 61-year-old man was admitted to our hospital because of fatigue and myasthenia in the extremities, and small-cell lung carcinoma with pulmonary metastasis was diagnosed, together with SIADH and LEMS. These syndromes markedly ameliorated following tumor shrinkage, with 4 cycles of chemotherapy consisting of carboplatin and etoposide. On progression of the tumor thereafter, neither syndrome recurred. A literature review disclosed that these syndromes frequently resolve with tumor shrinkage.

The Use of Electronic Medical Records-Based Big-Data Informatics to Describe ALT Elevations Higher than 1000 IU/L in Patients with or without Hepatitis B Virus Infection.

Hepatitis B virus (HBV) infection is one of the serious health problems in the world as HBV causes severe liver diseases. Moreover, HBV reactivation has occasionally been observed in patients with resolved HBV infection and patients using immunosuppression and anticancer drugs. Large-scale hospital data focused on HBV infection and severe liver function were analyzed at our hospital, located in an urban area adjacent to Tokyo, the capital city of Japan. A total of 99,932 individuals whose blood samples were taken at 7,170,240 opportunities were analyzed. The HBV surface antigen (HBsAg)-positive group had a more frequent prevalence of patients with higher transaminase elevations than the HBsAg-negative group. However, among the HBsAg-negative group, patients who were positive for anti-HBV surface antibody and/or anti-HBV core antibody, had more severe liver conditions and fatal outcomes. More careful attention should be paid to alanine transaminase (ALT) elevations higher than 1000 IU/L in patients who had current and previous HBV infection.

Monokine induced by interferon-gamma (MIG/CXCL9) is derived from both donor and recipient sources during rejection of class II major histocompatibility complex disparate skin allografts.

Chemokines, including monokine induced by interferon-gamma (Mig/CXCL9), are produced both in allografts and during the direct T-cell infiltration that mediates graft rejection. Neither the specific production nor contribution of allograft donor versus recipient Mig in allograft rejection is currently known. C57BL/6 mice with a targeted deletion in the Mig gene were used as both skin allograft donors and recipients in a class II major histocompatibility complex-mismatched graft model to test the requirement for donor- versus recipient-derived Mig for acute rejection. B6.Mig(-/-) allografts had a 10-day prolonged survival in B6.H-2(bm12) recipients when compared with wild-type C57BL/6 allograft donors, and B6.H-2(bm12) skin allografts had a 5-day prolonged survival in B6.Mig(-/-) versus wild-type recipients. Transplantation of B6.Mig(-/-) skin grafts onto B6.H-2(bm12).Mig(-/-) recipients resulted in further prolonged allograft survival with more than 30% of the grafts surviving longer than 60 days. Prolonged allograft survival was also associated with delayed cellular infiltration into grafts but not with altered T-cell proliferative responses to donor stimulators. Immunohistochemical staining of allograft sections indicated that Mig is produced by both donor- and recipient-derived sources, but Mig from each of these sources appeared in different areas of the allograft tissue. These results therefore demonstrate the synergy of donor- and recipient-derived Mig in promoting T-cell infiltration into allografts.

Contralateral metachronous tumor occurrence is more frequently associated with distant metastases or postoperative intrarenal recurrence in renal cell carcinoma patients.

OBJECTIVE: To analyze the prognosis of patients with sporadic bilateral renal cell carcinoma (RCC). METHODS: From January 1979 to December 2007, 984 patients with sporadic RCC underwent surgery at our department. Of these, 53 patients (5.7%) presenting with bilateral RCC were included in this retrospective analysis. RESULTS: Thirty-one of the 53 bilateral RCC patients had synchronous RCC, and 22 had metachronous RCC. Distant metastases by the time of the bilateral tumor occurrence were found in four patients (13%) in the synchronous group and in 10 patients (48%) in the metachronous group. No difference was found between the two groups in terms of overall survival. In contrast, survival after the second surgery in the metachronous group was significantly lower than that after the first surgery (P < 0.001) in the synchronous group (P = 0.02). In addition, the incidence of local recurrence after partial nephrectomy was higher in the metachronous group (26%) compared to the synchronous group (4%, P = 0.04) or the unilateral RCC patients (0.4%, P < 0.01). CONCLUSIONS: Metachronous occurrence of RCC in the contralateral kidney is associated with an unfavorable prognosis, suggesting that metachronous contralateral tumors might be metastasis of the original tumors. A stricter follow-up schedule is advisable for metachronous bilateral RCC patients.

[Case of thymic carcinoid associated with multiple endocrine neoplasia type I treated effectively with chemotherapy].

A 53-year-old man was referred to our hospital due to a mediastinal mass found during a medical checkup in July 2009. He had a past history of hyperparathyroidism, for which he underwent surgery in 1994, and also had a family history in that his sister had multiple endocrine neoplasia type 1 (MEN1). He was given a diagnosis of MEN I on genetic testing. Chest CT revealed a mediastinal mass 4 cm in maximum dimension, and an atypical carcinoid was diagnosed according to mediastinal biopsy findings. Bone metastasis was detected and he was given cisplatin and etoposide. The tumor decreased in size by 30%, and was evaluated as showing partial response. Although there are some cases of MEN-related thymoma treated by surgery, a case which successfully responded to chemotherapy alone is thought to be extremely rare.

Pembrolizumab for Previously Untreated Patients with Advanced Non-small-cell Lung Cancer and Preexisting Interstitial Lung Disease.

Objective Pembrolizumab has benefited patients with advanced non-small-cell lung cancer (NSCLC) with a programmed death-ligand (PD-L) 1 high expression, but little information is available regarding its safety for patients with interstitial lung disease (ILD). The aim of this study was to assess the efficacy and tolerability of pembrolizumab for patients with advanced NSCLC and preexisting ILD. Methods We retrospectively reviewed the medical records of five patients with advanced NSCLC and preexisting ILD who received pembrolizumab monotherapy in a first-line setting. Patients All patients had mild ILD and pulmonary emphysema with a forced vital capacity within the normal range. Pembrolizumab was administered at a dose of 200 mg/body on day 1 every 3 weeks. Results The overall response rate was 60%. Four patients developed pembrolizumab-induced lung injury, which was improved in all cases by corticosteroid therapy. One patient received pembrolizumab for two years, did not experience lung injury and achieved a complete response. Conclusion Pembrolizumab has a high risk of inducing lung injury in patients with preexisting ILD, although it may be very effective in NSCLC patients with a high PD-L1 expression, even concurrent with preexisting ILD. Further large-scale studies are needed to determine risk factors of pembrolizumab-induced lung injury in such patients.

Cytomegalovirus infection following renal transplantation in patients administered low-dose rituximab induction therapy.

Anti-CD20 antibody (rituximab) is recently being used as a B cell-depleting agent in renal transplantation (RTx). However, the incidence of infectious complications associated with rituximab therapy remains uncertain. We evaluated the incidence of cytomegalovirus (CMV) infection associated with rituximab therapy in RTx. A total of 83 patients were enrolled. The immunosuppressive regimen consisted of tacrolimus or cyclosporin, mycophenolate mofetil, methylprednisolone and basiliximab. In 54 patients, only one dose of rituximab (200 or 500 mg/kg body weight) was given before RTx. A total of 25 of 43 (58.1%) recipients who were CMV seropositive prior to RTx and who received rituximab induction therapy developed CMV infection, compared to 18 of 24 (75%) CMV seropositive recipients who did not receive rituximab therapy (P = 0.1676). A total of 8 of 11 patients who were CMV seronegative prior to RTx and who received rituximab developed CMV infection. However, CMV seroconversion was seen in all 8 of these infected patients. Low-dose rituximab induction therapy in renal transplant recipients appears to have no influence on the incidence of CMV infection and CMV seroconversion. However, we have to consider anti-CMV prophylaxis therapy, because of high incidents of CMV infection, especially for CMV seronegative recipients who received rituximab.

[A case of sternoclavicular joint tuberculosis with renal failure due to rifampicin].

A 79-year-old man was admitted to a previous hospital complaining of left precordial swelling. Chest CT scan showed destruction of left sternoclavicular joint and a mass of 5 cm in diameter. Needle biopsy was performed and the diagnosis of sternoclavicular joint tuberculosis was made on the basis of presence of M. tuberculosis in the specimen. The patient was treated with isoniazid, ethambutol, rifampicin, and pyrazinamid but he developed renal failure. Then, he was transferred to our hospital. All medications were suspended because of the possibility of the side effect of drugs. We performed renal biopsy and histopathological examination revealed interstitial nephritis and minimal-change glomerulonephritis. From the result of examination, we considered interstitial nephritis was due to rifamicin. The treatment with 50 mg/day of prednisolone and isoniazid, ethambutol, and levofloxacin was administrated and renal failure and precordial mass were improved. Tuberculous arthritis usually affect hip and knee joint and sternoclavicular joint involvement is very rare.

[A cluster of paragonimiasis westermani infections in Thai immigrants].

We report a cluster of infections in four female Thai immigrants aged between 35 and 49 years who developed paragonimiasis westermani within 16 months of ingesting freshwater crabs purchased from a market in Japan. Their symptoms included cough, bloody sputum, chest pain, and dyspnea. Radiographic and CT findings comprised pleural effusion, pneumothorax, air-space consolidation, and nodular opacities. Paragonimus eggs were identified in the feces of one patient, and in the pleural effusion and the bronchoalveolar lavage fluid (BALF) of another. All diagnoses of paragonimiasis westermani were established by enzyme-linked immunosorbent assay (ELISA) of their serum. Paragonimiasis is a re-emerging disease in Japan. Moreover, since the number of immigrant patients is increasing, it is necessary to pay attention to infectious diseases resulting from their eating habits as well as imported diseases.

Pemetrexed Plus Platinum for Patients With Advanced Non-small Cell Lung Cancer and Interstitial Lung Disease.

BACKGROUND/AIM: Pemetrexed plus platinum followed by pemetrexed maintenance has been one of the standard first-line treatments in advanced nonsquamous non-small cell lung cancer (NSCLC), but little is known regarding its safety and efficacy for patients with interstitial lung disease (ILD). PATIENTS AND METHODS: The medical records of 24 patients with advanced nonsquamous NSCLC and preexisting ILD who received pemetrexed and platinum doublet therapy with and without pemetrexed maintenance in the first-line setting between December 2009 and June 2016, were retrospectively reviewed. RESULTS: The median progression-free survival time was 4.7 months, and the median overall survival time was 9.5 months. Of the 24 patients analyzed, six received pemetrexed maintenance. Acute exacerbation of ILD (AE-ILD) occurred in five (20.8 %) of 24 patients, including two fatal cases. CONCLUSION: The treatment with pemetrexed plus platinum has a high risk of AE-ILD in patients with advanced nonsquamous NSCLC and preexisting ILD.