Clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors / 中华内科杂志

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8+T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.

Clinical Features of Coccidioidomycosis:Analysis of 33 Chinese Cases / 中国医学科学院学报

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(=14),mediastinal lymphadenopathy(=5),solid shadow(=4),cavity(=4),pleural effusion(=3),multiple plaques(=2)and masses(=2).Coccidiolys cysts were detected in the affected tissues(=28)or in pus,exudate or pleural smear(=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(=20),systemic or local administration of amphotericin B(=13),surgical resection of the lesion(=8),and intravenous gamma globulin(=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 / 中国医学科学院学报

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 effectiveness and safety of different treatment modes for limited-stage small cell lung / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the effectiveness and safety of different treatment modes for limited-stage small cell lung cancer(SCLC).</p><p><b>METHODS</b>The clinical data of 171 SCLC patients who had received different therapies were retrospectively analyzed.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Concurrent radiochemotherapy is the treatment of choice for SCLC patients because it can improve the survival with tolerable toxicities.</p>

Recurrence patterns of advanced non-small cell lung cancer treated with gefitinib / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Geftinib is widely used in the treatment of advanced non-small cell lung cancer (NSCLC). However, only a small number of reports have described initial failure sites in patients treated with gefitinib. The aim of this study was to investigate survival, recurrence sites, and treatment after recurrence in these patients.</p><p><b>METHODS</b>A retrospective review was conducted of all patients with stage III/IV NSCLC treated with gefitinib in Peking Union Medical College Hospital from October 2002 to September 2011. Patient characteristics, initial failure sites, associated clinical factors, and subsequent therapy were included in the analysis of prognostic factors.</p><p><b>RESULTS</b>A total of 316 patients were identified The median progress free survival (PFS) and overall survival (OS) times were 238 days and 468 days, respectively. The median survival time after progression was 145 days. The sites of initial failure were lung (62.34%), bone (17.72%), central nerve system (CNS, 16.14%), liver (9.49%), and others (7.19%). Patients with single-site progression or multi-site progression were 81.01% and 18.99%, respectively. Progression-free survival time was associated with lung and bone failure. Additionally, the median survival time after progression was lower in patients with multi-site progression and liver progression. Other initial failure sites displayed no relationship with survival, including CNS failure. Subsequent therapy may affect survival after progression. In patients receiving continuous epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, radiotherapy, and re- treatment with EGFR-TKIs, survival time after progression was prolonged compared with the best supportive care.</p><p><b>CONCLUSIONS</b>Our data suggest that patients receiving gefitinib should be closely monitored regarding lung metastasis during follow-up. Liver metastases and multi-site progression were poor prognostic factors. After failure with gefitinib, patients may benefit from radiotherapy, chemotherapy, continuous EGFR-TKI therapy and re-treatment with EGFR-TKIs.</p>

Clinical and pathological analyses of bevacizumab-induced renal impairment in four patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical and pathological characteristics of bevacizumab-induced renal impairment.</p><p><b>METHOD</b>The clinical and pathological data of 4 patients with bevacizumab-induced renal impairment in Peking Union Medical College Hospital was retrospectively analyzed.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Therapeutic effects and prognostic factors for the limited-stage small cell lung cancer treated with multidisciplinary therapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Phase I trial of icotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in Chinese patients with non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer (NSCLC) in a Chinese patient population.</p><p><b>METHODS</b>This was an open-label, phase I, dose escalation, safety/tolerability trial of oral icotinib (100 to 400 mg), administered twice per day for 28-continuous-day cycles until disease progression or undue toxicity.</p><p><b>RESULTS</b>Forty patients with stage IIIB (15%) or IV (85%) NSCLC were included in the study. They had mainly adenocarcinoma (85%), with a performance status (PS) of 0 (45%) or 1 (55%) and less than half the patients (45%) had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash (25%), diarrhea, nausea and abdominal distention. One definite interstitial lung disease (ILD) was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one (2.5%) patient receiving 150 mg gained complete response (CR) that persisted for 44 weeks, seven (17.50%) patients had partial remission (PR), and 18 (45%) patients had stable disease (SD). The objective response including CR + PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks (range: 12 to 32 weeks). The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose, response, adverse effect, or duration of the study was observed.</p><p><b>CONCLUSIONS</b>Icotinib, given as oral twice daily, showed favorable safety and tolerability. Mild and reversible rash, diarrhea, and nausea were the main adverse events. Antitumor activity was obvious at each dose in heavily pretreated patients. Pharmacodynamic evaluations and further phase II/III trials are in progress.</p>

Comparison of three methods for detecting epidermal growth factor receptor mutations in plasma DNA samples of Chinese patients with advanced non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epidermal growth factor receptor (EGFR) mutations can predict tumor response to tyrosine kinase inhibitors (TKIs). Detecting EGFR mutations in plasma DNA samples in patients with advanced non-small cell lung cancer is challenging and promising. We compared three methods for detecting plasma EGFR mutations, including direct DNA sequencing, denaturing high-performance liquid chromatography (DHPLC) and Scorpions Amplification Refractory Mutation System (Scorpions ARMS).</p><p><b>METHODS</b>Plasma DNA samples from 73 patients with stage IIIB to IV adenocarcinoma were analyzed for EGFR mutations in exons 19 (deletion mutation) and 21 (L858R mutation) using direct DNA sequencing, DHPLC and Scorpions ARMS. Sensitivities of the three methods were compared and the relationship between EGFR mutations and patients' survival was analyzed.</p><p><b>RESULTS</b>In 73 patients, we detected EGFR mutations in 5 samples (6.9%) by direct DNA sequencing, in 22 samples (30.1%) by DHPLC, and in 28 samples (38.4%) by Scorpions ARMS. EGFR mutations were found in 13 samples in exon 19 and in 9 samples in exon 21 by DHPLC, while we found mutations in 15 samples in exon 19 and in 13 samples in exon 21 by Scorpions ARMS. Among the 73 patients, there was 90.4% concordance between DHPLC and Scorpions ARMS (66/73, κ = 0.79, P = 0.07). Of the 73 patients, 46 patients were treated with gefitinib, including 18 patients with mutations and 28 patients without mutations as determined by Scorpions ARMS. The 18 patients with mutations had a significantly longer progression-free survival (PFS) time (median PFS was 21.0 months) than the 28 patients without mutations (median PFS was 7.0 months) (P = 0.022).</p><p><b>CONCLUSIONS</b>Among the three methods for detecting EGFR mutations in plasma DNA samples of patients with advanced lung adenocarcinoma, direct gene sequencing had the lowest sensitivity, while Scorpion ARMS showed the highest mutation detecting capability. DHPLC is slightly less sensitive than Scorpion ARMS. EGFR mutations in exons 19 (deletion mutation) and 21 (L858R mutation) predict a longer PFS.</p>

Efficacy and safety of erlotinib as monotherapy for advanced non-small cell lung cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the efficacy and safety of erlotinib monotherapy for advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>Erlotinib monotherapy is safe and effective for some Chinese NSCLC patients after failure of prior chemotherapy.</p>

Clinical features of pulmonary malignancies in patients younger than 30 years of age / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyse the clinical features of young patients with pulmonary malignancies.</p><p><b>METHOD</b>The clinical data of 58 young (< 30 years) patients with pulmonary malignancies who were treated in our hospital were retrospectively analyzed.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>The pulmonary malignancies in young patients tend to be complicated. The treatment strategy should be based on the specific conditions of each patient.</p>

Efficacy and clinical/molecular predictors of erlotinib monotherapy for Chinese advanced non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A retrospective analysis of clinical data were conducted reviewing patients who were given erlotinib at Peking Union Medical College (PUMC) Hospital from May 2005 to December 2009. Relationships between clinical factors, epidermal growth factor receptor (EGFR) mRNA expression, EGFR gene mutations, KRAS gene mutations and clinical outcomes were investigated in Chinese patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Patients with stage IIIB/IV NSCLC who had not previously participated in erlotinib related clinical trials were enrolled into this study. All patients were given oral erlotinib 150 mg per day. Tumor samples of some patients were accessed with mutant-enriched polymerase chain reaction assay (EGFR, KRAS gene mutations) and multiplex branched DNA assay (EGFR mRNA expression).</p><p><b>RESULTS</b>Seventy-nine patients were enrolled in this study, 23 patients had a partial response (PR), 36 patients had a stable disease (SD), 20 patients had a PD, with an objective response rate of 29.1%, and a disease control rate of 74.7%. Females (P = 0.023), non-smokers (P = 0.013), patients with a skin rash (P = 0.047), and with highly differentiated tumors (P = 0.037) were significantly correlated with the objective response rate. Patients with a lower ECOG PS (P = 0.002), highly differentiated tumors (P = 0.014), non-smokers (P = 0.002), and patients with a skin rash (P < 0.001) were significantly correlated with the disease control rate. The median progression-free survival was 35 weeks (95%CI: 13 - 57 weeks) and 1-year survival was 72.3%. Highly-differentiated tumors (P = 0.027) and patients with a skin rash (P < 0.001) were significantly correlated with PFS. Seventeen patients were tested for EGFR/KRAS gene mutations and EGFR mRNA expression. Progression-free survival (PFS) of patients with EGFR exon 19/21 mutations was 66 weeks, longer than patients with wild type EGFR exon 19/21 (P = 0.018). No significant relationships were found between EGFR mRNA expression, EGFR exon 19/21 mutations, and KRAS mutations and objective response rate or disease control rate. The most common adverse events were skin rash (60.9%) and diarrhea (26.6%).</p><p><b>CONCLUSIONS</b>Erlotinib was safe and effective in treating Chinese patients with advanced NSCLC. The PFS of patients who had a skin rash, highly differentiated tumors, or EGFR exon 19/21 mutations was significantly longer.</p>

Efficacy and safety of gefitinib in maintenance therapy for patients with advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of gefitinib as maintenance therapy for patient with advanced non-small lung cancer (NSCLC).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Maintenance therapy with gefitinib after induction chemotherapy may improve overall survival in patient with non-small cell lung cancer.</p>

Gefitinib in the treatment of advanced non-small cell lung cancer with brain metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Brain metastasis is frequently found in patient with advanced non-small cell lung cancer. Gefitinib is a inhibitor of epidermal growth factor receptor and can be used for the treatment of advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the antitumor efficacy of Gefitinib in advanced NSCLC patients with brain metastasis.</p><p><b>METHODS</b>Forty-four consecutive NSCLC patients with brain metastases were treated with gefitinib, which was administered orally at daily dose of 250 mg. Of these patients, 30 had been treated with WBRT and 42 received chemotherapy one month before enrolled into the study.</p><p><b>RESULTS</b>Partial response (PR) was observed in 14 patients (31.8%), stable disease (SD) in 21 (47.7%) with an overall disease control rate of 79.5%. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 13.0 months. The difference in disease control rate between the patients who had previous WBRT and those without was not significant (P = 0.566). The toxicity is mild and tolerable.</p><p><b>CONCLUSION</b>Our data shows that Gefitinib is safe and may be effective on brain metastasis, which may become an alternative treatment option for the patient with advanced NSCLC.</p>

Transbronchial needle aspiration in the diagnosis of bronchogenic carcinoma with enlarged mediastinal and /or hilar lymph nodes / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the role of transbronchial needle aspiraion (TBNA) in the diagnosis of bronchogenic carcinoma with enlarged mediastinal and/or hilar lymph node.</p><p><b>METHODS</b>Patients with mediastinal and/or hilar lymphoadenopathy proven by CT scan were eligible for TBNA as reported by WANG. All specimen was directly and instantly smeared for cytological examination.</p><p><b>RESULTS</b>From June 2004 to May 2006, 77 such patients were examined: including 38 lung cancers, 35 lung benign diseases and 4 without definite diagnosis. All TBNA procedures were successfully carried out in 222/225 ( 98.7%). Positive TBNA rate was 81.6% (31/38) in patients who had been proven to suffer from bronchogenic carcinoma. The diagnosis of lung cancer was confirmed via TBNA only in 9 patients. A total of 63 lymph nodes in the 38 lung cancer patients were aspirated by TBNA with a positive rate of 65.1% (41/63). The sensitivity of TBNA was significantly correlated with pathology type, lymph node size and experience of the cytologist. Severe complications were rare except small amount of bleeding at the TBNA site (52/77, 67.5%).</p><p><b>CONCLUSION</b>TBNA is quite safe and helpful in diagnosis and staging of bronchogenic carcinoma, yet it is not helpful in diagnosis of benign lung diseases.</p>

Efficacy and safety of arbidol in treatment of naturally acquired influenza / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Arbidol in the treatment of naturally acquired influenza.</p><p><b>METHODS</b>A randomized, double-blinded, placebo controlled trial was conducted. Subjects were enrolled. The inclusion criteria included: aged 18 to 65 years, presented within 36 hours of onset of influenza symptoms; and had documented temperature of 37.8 degrees C or higher during an influenza outbreak in the community. Individuals were randomly divided Arbidol group (200 mg three times daily for 5 days) or placebo group.</p><p><b>RESULTS</b>Totally 232 individuals were recruited and received medication and follow-up. All of them were qualified to be analyzed for safety as intent-to-treat population (ITT) (113 Arbidol, 109 placebo). Twenty-two (9.48%) were during follow-up or refused to continue the trial, and 210 completed as schecule and identified as PP population (102 Arbidol, 108 placebo). Totally 125 individuals were identified as influenza-infected through laboratory test, which was defined as PPi population (59 Arbidol, 66 placebo). In PPi population, the cumulative alleviation proportion of Arbidol group was significantly higher than that of placebo group. The median duration of illness was 72.0 hours (95% confident interval (CI) 66.00-78.00 hours) in Arbidol group and 96.0 hours (95% CI 87.46-104.54 hours) in placebo group. The median area under the curve (AUC) of decreased total score were significantly higher in Arbidol group than in placebo group, which were 780.00 and 684.00 score-hours respectively. For PP population, similar results were seen. Adverse events reported were similar in Arbidol group and in placebo group. The main adverse events were gastrointestial symptoms and increased transaminase.</p><p><b>CONCLUSION</b>Arbidol was effective and well tolerated in the treatment of early naturally acquired influenza.</p>

Clinical diagnosis, treatment and prognosis of elderly SARS patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To discuss the clinical manifestations, therapeutic strategy and prognosis of patients with severe acute respiratory syndrome (SARS) older than 60 years.</p><p><b>METHODS</b>Elderly patients diagnosed as SARS in Peking Union Medical College Hospital were compared with younger patients.</p><p><b>RESULTS</b>Twenty-four elderly patients and 53 younger patients were analysed. Elderly patients had more coexisting conditions, such as hypertension, diabetes, coronary heart disease, and renal disease than control group (P < 0.05). Rate of respiratory failure in elderly patients was higher than that in control group (P < 0.05). Elderly patients had more respiratory symptoms, such as cough, sputum, and shortness of breath (P < 0.05). Rate of lymphocytopenia and thrombocytopenia in elderly patients was higher than that in control group. All patients were given ribavirin and antibiotics. More patients in elderly group were given 3rd generation cephalosporin and imipenem. Mortality rate in elderly group was higher than that in control group (33.3% vs 3.8%, P < 0.05). Univariate analysis showed that age, respiratory failure, and thrombocytopenia were risk factors of death, but logistic analysis did not find any independent risk factor.</p><p><b>CONCLUSIONS</b>Though the elderly patients have a lower morbidity of SARS, they have more coexisting conditions. The therapy of elderly patients is more difficult than that of control group, and the mortality in elderly patients is high.</p>

Numerical Taxonomy and 16S rDNA PCR-RFLP of Rhizobial Strains Isolated from Psoralea corylifolia etc / 微生物学通报

24 strains obtained from root nodules of Psoralea corylifolia, Pueraria lobata, and Campylotropis macrocarpa of Yunnan province were studied with numerical taxonomy and 16S rDNA PCR-RFLP. Results of numerical taxonomy indicated that all strains included 10 reference strains were divided into 3 groups at 84% similarity. Group III is an unknown group with no reference strains. Group I is slow-growing kind, and group II fast and middle-slow-grower. The dendrogram derived from 16S rDNA PCR-RFLP showed that all strains divided into five phylogenetic branches at the similarity of 70%. They are branches I and V with no reference strains, Agrobacterium-Sinorhizobium-Rhizobium, Mesorhizobium and Bradyrhizobium. Not all results of numerical taxonomy are accord with 16S rDNA PCR-RFLP, and 2 strains at the same group with A. tumefaciens IAM13129T.