BAG3-Related Myofibrillar Myopathy Presenting as Hypercapnia: A Case Report and Literature Review.

Objective BAG3-related myopathy is a rare condition so far reported in twenty patients worldwide. The purpose of this study was to draw attention to this rare disease and to the fact that BAG3-related myopathy should be considered as a rare differential diagnosis of hypercapnia. Methods We report a sporadic case of a 14-year-old Chinese girl with a de novo p.Pro209Leu mutation in BAG3 and reviewed the literatures for reported cases related to this mutation. Results We described a 14-year-old Chinese girl who presented with gradually appearing symptoms of hypercapnia that required assisted ventilation. The muscle biopsy and the blood whole-exome sequencing results confirmed the diagnosis of myofibrillar myopathy with a de novo p.Pro209Leu mutation in BAG3. Totally twenty-one patients from twenty families with a confirmed diagnosis of BAG3-related myopathy were reported to date, including this patient and literature review. The male to female ratio was 11:10 and most showed initial symptoms in the first decade of life. Most patients presented toe/clumsy walking or running as the onset symptom, followed by muscle weakness or atrophy. Creatine kinase levels were elevated in fourteen patients and were normal in three. Eighteen patients developed respiratory insufficiency during the disease course and thirteen (one could not tolerate non-invasive assisted ventilation) required non-invasive assisted ventilation for treatment. Except for one not reported, heart involvement was found in seventeen patients during the disease course and seven underwent heart transplantation. Z-disk streaming and aggregation could be observed in most of the patients' muscle histology. In the long-term follow-up, five patients died of cardiac or respiratory failure. Conclusion BAG3-associated myopathy is a rare type of myofibrillar myopathy. It should be considered as a rare differential diagnosis of hypercapnia.

[Clinical Features of Coccidioidomycosis:Analysis of 33 Chinese Cases].

Objective To summarize the characteristics of Chinese coccidioidomycosis cases, improve the diagnosis and treatment of this disease and prevent misdiagnosis as well as therapeutic error.Methods Search in databases including Medline,Wanfang,and CNKI using "Coccidioidomycosis" and "China" as index words yielded 23 articles that reported a total of 32 Chinese coccidioidomycosis cases.In addition,one patient with disseminated coccidioidomycos was treated in our center in April 2016.The demographic data,site of infection,clinical manifestations,past medical history,exposure history,imaging and laboratory findings,and pathological features of these 33 patients were analyzed.Results Among these 33 patients,7(21.2%)had visited an epidemic area and 6(18.2%)were immunocompromised.The disease involved the respiratory system,skin,bone,central nervous system,cornea,and stomach in 24,6,3,2,1,and 1 patients,respectively.Eight patients (24.2%) had multiple system involvement,and three of them died.The imaging findings included pulmonary nodules(n=14),mediastinal lymphadenopathy(n=5),solid shadow(n=4),cavity(n=4),pleural effusion(n=3),multiple plaques(n=2)and masses(n=2).Coccidiolys cysts were detected in the affected tissues(n=28)or in pus,exudate or pleural smear(n=3);in addition,coccidioides mycelium and spores were found in the sputum,pus,and tissue cultures in 4 cases,among whom only 2 cases were confirmed by serological examination.The treatments included triazoles(n=20),systemic or local administration of amphotericin B(n=13),surgical resection of the lesion(n=8),and intravenous gamma globulin(n=1).Five patients died,among whom three had underlying diseases that caused immunosuppression and one was an infant.The prognoses were relatively good in the remaining patients.Conclusions Early diagnosis and proper treatment can achieve good prognosis in coccidioidomycosis patients.Multi-system involvement and immunosuppression are risk factors for poor prognosis of coccidioidomycosis.For these patients,adequate and full-course medication may prevent rapid disease progression.

Detection of Echinoderm Microtubule Associated Protein Like 4-Anaplastic Lymphoma Kinase Fusion Genes in Non-small Cell Lung Cancer Clinical Samples by a Real-time Quantitative Reverse Transcription Polymerase Chain Reaction Method.

Objective To establish a real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) for the rapid, sensitive, and specific detection of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes in non-small cell lung cancer. Methods The specific primers for the four variants of EML4-ALK fusion genes (V1, V2, V3a, and V3b) and Taqman fluorescence probes for the detection of the target sequences were carefully designed by the Primer Premier 5.0 software. Then, using pseudovirus containing EML4-ALK fusion genes variants (V1, V2, V3a, and V3b) as the study objects, we further analyzed the lower limit, sensitivity, and specificity of this method. Finally, 50 clinical samples, including 3 ALK-fluorescence in situ hybridization (FISH) positive specimens, were collected and used to detect EML4-ALK fusion genes using this method. Results The lower limit of this method for the detection of EML4-ALK fusion genes was 10 copies/µl if no interference of background RNA existed. Regarding the method's sensitivity, the detection resolution was as high as 1% and 0.5% in the background of 500 and 5000 copies/µl wild-type ALK gene, respectively. Regarding the method's specificity, no non-specific amplification was found when it was used to detect EML4-ALK fusion genes in leukocyte and plasma RNA samples from healthy volunteers. Among the 50 clinical samples, 47 ALK-FISH negative samples were also negative. Among 3 ALK-FISH positive samples, 2 cases were detected positive using this method, but another was not detected because of the failure of RNA extraction. Conclusion The proposed qRT-PCR assay for the detection of EML4-ALK fusion genes is rapid, simple, sensitive, and specific, which is deserved to be validated and widely used in clinical settings.

Comparison of epidermal growth factor receptor mutation statuses in tissue and plasma in stage I-IV non-small cell lung cancer patients.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations play essential roles in the treatment of non-small cell lung cancer (NSCLC) patients using EGFR tyrosine kinase inhibitors. Detection of EGFR mutations in blood cell-free DNA (cfDNA) seems promising. However, the mutation status in the plasma/serum is not always consistent with that in the tissues. OBJECTIVES: The aims of this study were to compare the mutation statuses in plasma to those in tissues and thus to determine the specific subgroups of NSCLC patients who may be the best candidates for EGFR mutation analyses using blood cfDNA. METHODS: A total of 111 pairs of tissue and plasma samples were collected. Mutant-enriched PCR and sequencing analyses were performed to detect EGFR exon 19 deletions and exon 21 L858R mutations. RESULTS: Mutations were discovered in 43.2% (48/111) of the patients. The overall rate of consistency of the EGFR mutation statuses for the 111 paired plasma and tissue samples was 71.2% (79/111). The sensitivity and specificity rates of detecting EGFR mutations in the plasma were 35.6% (16/45) and 95.5% (63/66), respectively. The disease stage and tumor differentiation subgroups showed significantly different detection sensitivities; the sensitivity was 10% in early-stage patients and 56% in advanced-stage patients (p = 0.0014). For patients with poorly differentiated tumors, the sensitivity was 77.8%, which was significantly different from those with highly differentiated (20%; p = 0.0230) and moderately differentiated tumors (19%; p = 0.0042). CONCLUSION: Blood analyses for EGFR mutations may be effectively used in advanced-stage patients or patients with poorly differentiated tumors.

[Comparison of effectiveness and safety of different treatment modes for limited-stage small cell lung].

OBJECTIVE: To compare the effectiveness and safety of different treatment modes for limited-stage small cell lung cancer(SCLC). METHODS: The clinical data of 171 SCLC patients who had received different therapies were retrospectively analyzed. RESULTS: Of these 171 patients,55 had received concurrent radiochemotherapy,66 received sequential radiochemotherapy,and 50 received chemotherapy alone. For these 171 patients,the overall response rate(ORR)was 73.1%,overall survival(OS)and progression-free survival(PFS)were 23.5 months and 15.2 months,respectively,and the 1-,3-,and 5-year survival rates were 76.2%,30.4%,and 16.3%,respectively. For the concurrent group,sequential group,chemotherapy alone group,the median OS were 30.6,23.1,and 19.1 months,the median PFS were 19.7,13.3,and 11.5 months,and the 5-year survival rate was 28.7%,13.6%,and 9.4%,respectively(all P<0.05). The main toxic effects were myelosuppression,radiation pneumonia,and radiation esophagitis. The incidences of 1-2 grade myelosuppression were 92.7%,89.4%,and 92% in the concurrent group,sequential group,and chemotherapy alone group(P=0.25). For concurrent group and sequential group,the incidence of 1 grade radiation pneumonia were 47.2% and 50%,respectively(P=0.61),whereas the incidence of 1-2 grade radiation esophagitis were 94.5% and 75.8%(P=0.02). Multivariate analysis showed that gender,ECOG score,TNM stage,and thoracic radiation therapy were the independent prognostic factors for SCLC. CONCLUSION: Concurrent radiochemotherapy is the treatment of choice for SCLC patients because it can improve the survival with tolerable toxicities.

[Therapeutic effects and prognostic factors for the limited-stage small cell lung cancer treated with multidisciplinary therapy].

OBJECTIVE: To study the differences of objective response rate (ORR), side effects and survival among patients with limited-stage small cell lung cancer (LD-SCLC), who received concurrent chemoradiotherapy, sequential chemoradiotherapy or chemotherapy alone, and to analyze the influencing factors on their survival. METHODS: One hundred and sixty-six patients diagnosed as LD-SCLC in Peking Union Medical College Hospital from January 2000 to December 2009 were included in this study. The differences of objective response rates, side effects and survival rates were analyzed by χ2 test. Kaplan-Meier test was used to calculate the overall survival (OS) and progress-free survival (PFS). Cox regression was used to detect the influencing factors on survival time of the patients. RESULTS: The patients were divided into three groups: concurrent chemoradiotherapy (49 cases), sequential chemoradiotherapy (62 cases) and chemotherapy alone (55 cases). The chemotherapy was based on CE/EP regimen, with an average cycle of 5.2. Radiotherapy was of a common or 3-dimensional conformal technology, for regular segmentation irradiation with an average dose of 49.6 Gy. The total ORR was 73.4%, OS and PFS were 22.9 months and 10.8 months, 1, 3, 5-year survival rates were 82.7%, 31.8%, 18.6%, respectively. For the concurrent group, sequential group and chemotherapy alone group, the ORR was 89.4%, 67.2% and 66.0%, respectively. Compared the chemotherapy alone group and concurrent group with the sequential group, there were significant differences (P<0.05). For the concurrent group, sequential group and chemotherapy alone group, the median OS was 29.7 months, 22.6 months, and 19.5 months; the median PFS was 12.7 months, 10.8 months, and 9.8 months, respectively, with a non-significant difference between each two groups (P>0.05). For the concurrent group, sequential group and chemotherapy alone group, the 1-year survival rates were 91.1%, 86.3%, and 65.6%, the 3-year survival rates were 44.2%, 28.3% and 22.8%, and the 5-year survival rates were 24.2%, 21.4% and 11.1%, respectively, with significant differences among them (P<0.05). The major side effects were myelosuppression, gastrointestinal reactions, radiation pneumonia and radiation esophagitis. For the concurrent group, sequential group and chemotherapy alone group, the incidence of myelosuppression were 84.4%, 76.8% and 60.0%, respectively, with a significant difference (P=0.008) between the concurrent group and chemotherapy alone group. For the concurrent group and sequential group, the incidences of radiation pneumonia were 22.2% and 22.9%, with a non-significant difference (P=0.940). The incidences of radiation esophagitis were 47.2% and 16.7%, respectively, with a significant difference (P=0.002). Multivariate analysis showed that OS was significantly associated with gender (P=0.018) and ECOG score (P=0.009), and PFS was significantly associated with gender (P=0.050). CONCLUSIONS: For LD-SCLC, concurrent chemoradiotherapy can significantly increase the objective response rate. Concurrent chemoradiotherapy and sequential chemoradiotherapy compared with chemotherapy alone can extend survival, and concurrent chemoradiotherapy is better, but the differences among the three regimens are not significant. Gender and ECOG score are important influencing factors of survival.

[Clinical and pathological analyses of bevacizumab-induced renal impairment in four patients].

OBJECTIVE: To investigate the clinical and pathological characteristics of bevacizumab-induced renal impairment. METHOD: The clinical and pathological data of 4 patients with bevacizumab-induced renal impairment in Peking Union Medical College Hospital was retrospectively analyzed. RESULTS: There were 2 men and 2 women aged (56.5±11.5) years. Before bevacizumab treatment, three non-small cell lung cancer patients (75%) had normal renal function and only one pancreatic cancer patient (25%) had mild renal impairment. After 2-14 cycles of bevacizumab treatment, the most common clinical manifestation of bevacizumab-induced renal injury was proteinuria (>3.5 g/d) (n=4, 100%). Other clinical symptoms included microscopic hematuria (n=2, 50%), malignant hypertension (n=1, 25%), elevated serum creatinine level as accompanied with acute renal failure (n=1, 25%), and anuria (n=1, 25%). Thrombotic microangiopathy was the main pathological type (n=2, 50%), whereas other pathological types included membranoproliferative glomerulonephritis (n=1, 25%) and benign arteriolar nephrosclerosis (n=1, 25%). After the detection of renal impairment, bevacizumab therapy was stopped in all 4 cases (100%). Hemodialysis was performed in the patient with acute renal failure. The prognosis was relatively good. The renal function and proteinuria was completely recovered in one patient (25%), whereas the other three patients (75%) presented with persistent alleviated proteinuria but normal renal function. CONCLUSIONS: Bevacizumab may cause renal injury via complex mechanisms. Therefore, urine protein excretion and renal function should be closely monitored during bevacizumab treatment to identify any renal injury. The prognosis is relatively good after discontinuation of bevacizumab.

Characterization of driver mutations in Chinese non-small cell lung cancer patients using a novel targeted sequencing panel.

Background: The identification of driver mutations has greatly promoted the precise diagnosis and treatment of non-small cell lung cancer (NSCLC), but there is lack of targeted sequencing panels specifically designed and applied to Chinese NSCLC patients. This study aimed to design and validate of a novel sequencing panel for comprehensive characterization of driver mutations in Chinese NSCLC patients, facilitating further exploration of downstream pathway alterations and therapeutic utility. Methods: A novel target sequencing panel including 21 driver genes was designed and examined in a cohort of 260 Chinese NSCLC patients who underwent surgery in Peking Union Medical College Hospital (PUMCH). Genetic alterations were identified and further analyzed for driver mutations, downstream pathways and therapeutic utilities. Results: The most frequently identified driver mutations in PUMCH NSCLC cohort were on genes TP53 (28%), EGFR (27%) and PIK3CA (19%) for lung adenocarcinoma (LUAD), and TP53 (41%), PIK3CA (14%) and CDKN2A (13%) for lung squamous cell carcinoma (LUSC), respectively. Downstream pathway analysis revealed common pathways like G1_AND_S1_PHASES pathway were shared not only between LUAD and LUSC patients, but also among three different NSCLC cohorts, while other pathways were subtype-specific, like the unique enrichment of SHC1_EVENT_IN_EGFR_SIGNALING pathway in LUAD patients, and P38_ALPHA_BETA_DOWNSTREAM pathway in LUSC patients, respectively. About 60% of both LUAD and LUSC patients harbored driver mutations as sensitive biomarkers for different targeted therapies, covering not only frequent mutations like EGFR L858R mutation, but also rare mutations like BRAF D594N mutation. Conclusions: Our study provides a novel target sequencing panel suitable for Chinese NSCLC patients, which can effectively identify driver mutations, analyze downstream pathway alterations and predict therapeutic utility. Overall it is promising to further optimize and apply this panel in clinic with convenience and effectiveness.

Case Report: A Programmed Cell Death-1 Inhibitor-Related Abdominal Fibroinflammatory Reaction Affecting Multiple Organs in A Non-Small-Cell Lung Cancer Patient.

Immunotherapy utilizing programmed cell death-1 (PD-1)/PD-L1 inhibitors has been regarded as a rising hope for tumor patients, and their effects have been demonstrated in many clinical trials. However, immune-related adverse events also occur in patients and can sometimes have severe consequences. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD-1 antibody that has been approved by the US Food and Drug Administration for non-small-cell lung cancer. Here, we report a rare case of an abdominal fibroinflammatory reaction that affected multiple organs during anti-PD-1 immunotherapy using pembrolizumab in a non-small-cell lung cancer patient. The patient's case demonstrates that immunotherapy-related abdominal fibroinflammatory reactions need to be considered, especially for patients with a history of pre-existing conditions in the abdomen. Glucocorticoids may be useful as a treatment when a diagnosis is confirmed.

Gut microbiota shed new light on the management of immune-related adverse events.

Immunotherapy has dramatically revolutionized the therapeutic landscape for patients with cancer. Although immune checkpoint inhibitors are now accepted as effective anticancer therapies, they introduce a novel class of toxicity, termed immune-related adverse events, which can lead to the temporary or permanent discontinuation of immunotherapy and life-threatening tumor progression. Therefore, the effective prevention and treatment of immune-related adverse events is a clinical imperative to maximize the utility of immunotherapies. Immune-related adverse events are related to the intestinal microbiota, baseline gut microbiota composition is an important determinant of immune checkpoint inhibitor-related colitis, and antibiotics exacerbate these undesirable side-effects. Supplementation with specific probiotics reduces immune checkpoint inhibitor-related colitis in mice, and fecal microbiota transplantation has now been shown to effectively treat refractory immune checkpoint inhibitor-related colitis in the clinic. Hence, modifying the microbiota holds great promise for preventing and treating immune-related adverse events. Microbiomes and their metabolites play important roles in the potential underlying mechanisms through interactions with both innate and adaptive immune cells. Here we review the gut microbiota and immune regulation; the changes occurring in the microbiota during immune checkpoint inhibitor therapy; the relationship between the microbiota and immune-related adverse events, antibiotics, probiotics/prebiotics, and fecal microbiota transplantation in immune checkpoint inhibitor-related colitis; and the protective mechanisms mediated by the microbiome and metabolites in immune-related adverse events.

Clinical-radiological characteristics and intestinal microbiota in patients with pancreatic immune-related adverse events.

BACKGROUND: The pancreatic immune-related adverse event (irAE) is a rare but increasingly occurrence disease with limited knowledge, which was associated with the use of immune checkpoint inhibitors (ICIs). METHODS: In this case series study of pancreatic irAE patients, clinical and radiological manifestations are summarized. Baseline and post-treatment fecal microbiota of immune-related acute pancreatitis (irAP) patients were analyzed by the 16 s rDNA amplicon sequencing method. RESULTS: A total of six patients were enrolled into the study, and the onset of pancreatic irAEs occurred a median of 105 days after a median of 4.5 cycles with immune checkpoint inhibitors (ICIs). All patients had an effective response to ICIs. Abdominal pain was the main clinical manifestation. Serum amylase (sAMY) and lipase (sLIP) had dynamic changes parallel to clinical severity. Contrast-enhanced computed tomography (CT) did not accurately reveal the level of inflammation. However, magnetic resonance imaging (MRI) was a sensitive imaging method which showed decreased and increased signal intensity of pancreatic parenchyma in T1-weighted fat-saturated and diffusion-weighted imaging, respectively. Glucocorticoids were the main treatment with a rapid initial effect followed by a slow improvement. After reinitiation of ICI therapy, pancreatic irAEs either deteriorated, remained stable or the patient developed severe pancreatic ß-cell destruction without irAP recurrence. The baseline microbiota of irAP had low Bacteroidetes/Firmicutes ratio at phylum level, low relative abundance of Alistipes, Bacteroides and high Lachnospiraceae at genus level, compared to levels of pancreatic ß-cell destruction and post-treatment of irAP. CONCLUSIONS: Pancreatic irAE patients had corresponding abdominal pain and increase in sAMY/sLIP. MRI was found to be an ideal imaging modality. Treatment with glucocorticoids were the main approach. The microbiota showed relative changes at baseline and during treatment.

Clinical recommendations for perioperative immunotherapy-induced adverse events in patients with non-small cell lung cancer.

Perioperative adjuvant treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). In particular, the success of immune checkpoint inhibitors, such as antibodies against PD-1 and PD-L1, in patients with lung cancer has increased our expectations for the success of these therapeutics as neoadjuvant immunotherapy. Neoadjuvant therapy is widely used in patients with resectable stage IIIA NSCLC and can reduce primary tumor and lymph node stage, improve the complete resection rate, and eliminate microsatellite foci; however, complete pathological response is rare. Moreover, because the clinical benefit of neoadjuvant therapy is not obvious and may complicate surgery, it has not yet entered the mainstream of clinical treatment. Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancellation of surgery, additional illness, and even death, and have therefore attracted much attention. In this article, we draw on several sources of information, including (i) guidelines on adverse reactions related to immune checkpoint inhibitors, (ii) published data from large-scale clinical studies in thoracic surgery, and (iii) practical experience and published cases, to provide clinical recommendations on adverse events in NSCLC patients induced by perioperative immunotherapy.

[The efficacy and safety of pemetrexed as monotherapy for Chinese patients with advanced non-small cell lung cancer].

OBJECTIVE: To assess the outcome of pemetrexed as monotherapy for Chinese patients with advanced non-small cell lung cancer (NSCLC) at the Peking Union Medical College Hospital. METHODS: From February 2006 to August 2009, 69 patients with advanced NSCLC, including 36 (52.2%) men and 33 (47.8%) women, received pemetrexed monotherapy.Six patients had squamous cell carcinoma, 57 adenocarcinoma, 6 unspecified. Median survival (MS) and progress-free survival (PFS) were calculated using the Kaplan-Meier method. RESULTS: Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were gastrointestinal adverse events, skin rash, fever and fatigue. Total 5 cases with 3/4 grade AEs were reported, including fever, fatigue, rash, decreased platelets and elevated ALT/AST. The objective tumour response rate and stable disease rate were 10.1% (7/69) and 47.8% (33/69) respectively. Median PFS of all patients was 4.7 months (95%CI 3.0-6.4) and mean overall survival was 14.7 months (95%CI 11.5-17.9). CONCLUSIONS: Our study suggests that treatment with pemetrexed may be well-tolerated and beneficial for some Chinese patients after failure of prior chemotherapy. The rate of disease control is high and the frequency of 3/4 grade AEs is very low.

[Clinical features of pulmonary malignancies in patients younger than 30 years of age].

OBJECTIVE: To analyse the clinical features of young patients with pulmonary malignancies. METHOD: The clinical data of 58 young (< 30 years) patients with pulmonary malignancies who were treated in our hospital were retrospectively analyzed. RESULTS: Out of these 58 patients, adenocarcinoma was most common (n=23, 39.66%). Accompanied tumors were seen in two patients. Occupational or environmental factors were noted in two patients. Histories of smoking were noted in 10 patients (17.24%), and all of them were patients with epithelial tumor patients. Four patients had family history of tumors. The mean time from the onset of disease to confirmed diagnosis was (5.98+/-8.95) months. The initial misdiagnosis rate was 37.9% (n=23), with pulmonary tuberculosis as the most common misdiagnosis. The proportions of advanced-stage patients (stage III B and IV) and moderate to poor-differentiated tumor accounted for 59.26% (16/27) and 77.8% (14/18), respectively in 27 patients with non-small cell lung cancer. The proportion of tumors in limited stage was 72.73% in 11 patients with small cell lung cancer, and most patients (54.55) were not sensitive to conventional chemotherapy. In 6 patients with carcinoid, 4 patients were central and the other 2 patients were peripheral, and all of them presented as Cushing syndrome; CgA, AE1/AE3, Syn, and NSE were positive in immunohistochemical staining; and surgical operation was the main treatment for them. In 6 patients with carcinomas of salivary gland type, all cases were central; no lymph nodes metastasis was found in the postoperative specimen; and surgical operation was also the main treatment for these patients. In 3 patients with primitive neuroectodermal tumors, the tumors were highly malignant and invasive, and the development of primitive neuroectodermal tumors was closely related with pleura. Immunohistochemical staining showed that the tumor cells were positive for CD99. Multiple nodules in bilateral lungs were presented in 2 patients with anaplastic large cell lymphomas, in which CD30 was positive in tumor cells; chemotherapy was the main therapy for these two patients. In one patient with synovial sarcoma, the tumor was giant and highly malignant and invasive; it was divided into many cavities filled with bloody fluid and white cheese-like substances; immunohistochemical analysis showed positive vimentin and AE1/AE3. CONCLUSIONS: The pulmonary malignancies in young patients tend to be complicated. The treatment strategy should be based on the specific conditions of each patient.

[Efficacy and safety of erlotinib as monotherapy for advanced non-small cell lung cancer].

OBJECTIVE: To explore the efficacy and safety of erlotinib monotherapy for advanced non-small cell lung cancer (NSCLC). METHODS: Totally 50 patients with advanced NSCLC received oral erlotinib 150 mg/d treatment, and tumor specimen in 19 patients were collected for epidermal growth factor receptor (EGFR) gene mutation tests. Median survival (MS) was calculated using the Kaplan-Meier method. RESULTS: The most common adverse events (AEs) were skin rash (96%) and diarrhea (32%). The overall survival (OS) of all patients was 21.8 months 95% confidential interval (CI): 17.1-26.4 months and the median progression-free survival (PFS) of all patients was 7.0 months (95% CI: 3.9-10.1 months). EGFR mutation analysis showed gene mutation in 8 cases and wild type in 11 cases. The objective response rate in patients with or without EGFR gene mutations were 62.5% and 9.1%, respectively (chi(2)=6.631, P=0.036). PFS in patients with or without EGFR gene mutations were 16.330 (95% CI: 2.803-29.857 months) and 5.570 months (95% CI: 2.441-8.699 months), respectively (chi(2)=8.799, P=0.003). CONCLUSION: Erlotinib monotherapy is safe and effective for some Chinese NSCLC patients after failure of prior chemotherapy.

[The results of transbronchial needle aspiration in 164 cases with enlarged mediastinal and/or hilar lymph nodes].

OBJECTIVE: To evaluate the role of transbronchial needle aspiration (TBNA) in the diagnosis of patients with enlarged mediastinal and/or hilar lymph node. METHODS: Patients with mediastinal and/or hilar lymphoadenopathy proven by CT scan were eligible for TBNA as reported. All specimens were directly and instantly smeared for pathological examination. RESULTS: From June 1 2004 to December 31 2007, 164 patients were examined: including 80 lung cancers, 69 lung benign diseases, 2 other malignancy tumor, and 13 without definite diagnosis. Total 260 lymph nodes were punctured. TBNA procedures were successfully carried out in 445/463 (96.1%). Sensitivity of TBNA was 82.5% (66/80) in patients who had been proven to suffer from bronchogenic carcinoma. There were 25 patients that diagnosis of lung cancer was pathologically determined by TBNA only. A total of 122 lymph nodes in the 80 lung cancer patients were aspirated by TBNA with a positive rate of 65.6% (80/122). Severe complications were rare except small amount of bleeding at the TBNA site (100/164, 61.0%). From June 1 2006 to December 31 2007, lymph node tissues able to make histology diagnosis were yield in 73.5% (64/87) patients. Through histology pathology, the sensitivities of TBNA were 53.3% (8/15) for sarcoidosis and 78.6% (33/42) for lung cancer. CONCLUSION: TBNA is quite safe and helpful in diagnosis and staging of bronchogenic carcinoma, and in diagnosis of benign lung diseases.

[Efficacy and safety of gefitinib in maintenance therapy for patients with advanced non-small cell lung cancer].

OBJECTIVE: To evaluate the efficacy and safety of gefitinib as maintenance therapy for patient with advanced non-small lung cancer (NSCLC). METHODS: From Oct. 2002 to Apr. 2006, 173 patients with advanced NSCLC received oral gefitinib 250 mg per day after completion of induction chemotherapy (62 patients, maintenance therapy group) or recurrence after one or more regimens of chemotherapy (111 patients, recurrent group). Median survival (MS) and progress free survival (PFS) were calculated using the Kaplan-Meier method, and Cox regression analysis was used to analyze the difference between the sub-groups stratified by smoking, pathological type, liver metastasis and gefitinib treatment result. RESULTS: MS of maintenance therapy group and recurrent group were 25.0 months (95% CI: 19.3-30.7) and 12.5 months (95% CI: 9.3-15.7), respectively. There was a statistically significant difference between the above two groups (P = 0.0004). PFS of maintenance therapy group and recurrent group was 16.5 months (95% CI: 8.7-24.3) and 9.2 months (95% CI: 7.5-10.9), respectively. There was also a statistically significant difference between these two groups (P = 0. 0000). It was found that median MS in maintenance therapy group was significantly correlated with smoking status, pathology type, liver metastasis and objective response of gefitinib. CONCLUSION: Maintenance therapy with gefitinib after induction chemotherapy may improve overall survival in patient with non-small cell lung cancer.

[Evaluation of efficacy and safety of ZD1839 as monotherapy in Chinese patients with advanced non-small cell lung cancer].

OBJECTIVE: To report the outcome of gefitinib for Chinese patients with advanced nonsmall cell lung cancer(NSCLC) at Peking Union Medical College Hospital. METHODS: From Oct. 2002 to Apr. 2006, 204 patients with advanced NSCLC received oral ZD1839 (250 mg/d) treatment. The were 110 (59.9%) men and 94 (40.1%) women aged between 25 and 85 years. Thirty-two patients had squamous cell carcinoma, 125 adenocarcinoma, 30 bronchoalveolar carcinoma or adenocarcinoma with partial bronchoalveolar carcinoma, 6 adenosquamous carcinoma, and 11 unspecified. Twenty-six patients had no history of chemotherapy, 62 had no disease progression after chemotherapy, and 111 failed to prior one or more regimens. Median survival was calculated using the Kaplan-Meier method and a Cox regression analysis was used to detect differences in median survival between strata. RESULTS: The median survival of all patients and of patients failed to prior chemotherapy were 16.3 months (95% confidential interval CI, 14.5 - 18.2) and 12.5 months (95% CI 9.3 - 15.7). The rate of 1-year survival was 57%. The objective tumor response rate and stable disease rate were 31.4% and 41.7% respectively. The median survival were significantly related with ECOG scores, pathology types, disease progression after chemotherapy, objective efficacy of gefitinib and changes of short-breathing. Among 26 patients with no prior chemotherapy, the median survival was not statistically significant compared with that of other patients. Among the enrolled patients, 111 had disease progression and 62 had stable disease after prior chemotherapy, and their median survivals was statistically different. At the time of this analysis, 142 patients had disease progression, 58 of whom withdrew from taking gefitinib, and 84 continued gefitinib therapy until death. The median survivals for these subgroups were not significantly different. Among 142 patients with disease progression, 40 received other systemic treatment, the median survival was statistically significant compared with that of other patients. Objective response was significantly related with age, smoking status, pathological type, change of short-breathing and rashes induced by gefitinib. Adverse events were generally mild (grade 1 and 2) and reversible. The most frequent adverse events were rash 72.6% (138/190) and diarrhea 33.7% (64/190). CONCLUSION: Our study suggests that treatment with gefitinib maybe well tolerate and beneficial for some Chinese patients after failure of prior chemotherapy.

[Acute exacerbation of usual interstitial pneumonia and nonspecific interstitial pneumonia: analysis of 6 cases].

OBJECTIVE: Acute exacerbation of diffuse parenchymal lung disease (DPLD) is a condition in which patients with usual interstitial pneumonia (UIP), and other forms of interstitial lung disease, develops rapid respiratory failure, accompanied by extensive radiological infiltrates, and had no evidence of infection. The pathologic features of this condition are usually diffuse alveolar damage (DAD) and the outcome is poor. Our study was to define the clinicopathologic features and outcome of acute exacerbation in 3 patients with UIP and 3 with nonspecific interstitial pneumonia (NSIP). METHOD: The clinical data of the 6 patients from April 1999 to Jun 2007 were analyzed retrospectively. RESULTS: In the 6 patients, 2 were males. The median age was 51 yrs (29 -57 yrs). Three case had UIP [1 UIP/idiopathic pulmonary fibrosis (IPF), 1 UIP/dermatomyositis (DM), 1 UIP/UCTD], 2 had NSIP (1 idiopathic NSIP, 1 NSIP/DM), and 1 was diagnosed as DAD (the basic pathology was NSIP/DM) by autopsy. Four of the patients underwent video-assisted thoracoscopic surgery (VATS) for diagnosis, and 1 underwent CT-guided transthoracic needle biopsy. Two of them underwent surgical lung biopsy 1 week before acute exacerbation. Five cases had fever. Computed tomography data were available in all cases and showed the presence of extensive bilateral ground-glass opacities (5/6), sometimes accompanied by focal consolidation (2/6), superimposed on underlying fibrosis. The median oxygenation index was 200 (quartile range: 158-237) mm Hg (1 mm Hg = 0.133 kPa). Five patients were treated with corticosteroids, and in some combined with cyclophosphamide or intravenous immunoglobulin. Two patients survived the acute episode and were discharged from hospital. All 3 patients using mechanical ventilation died. CONCLUSIONS: Both UIP and NSIP can develop acute exacerbations. The trigger of acute exacerbation was unclear, but in some cases it maybe related to VATS. The clinical features include rapid respiratory failure, accompanied by extensive radiological infiltrates. The fatality is high. Corticosteroids or intravenous immunoglobulin may be helpful in the treatment of the condition.