重组人血管内皮抑素联合顺铂胸腔内注射治疗肺腺癌恶性胸腔积液的临床研究

目的研究重组人血管内皮抑素(恩度)联合顺铂胸腔内注射治疗肺腺癌恶性胸腔积液的近期疗效与安全性。方法 90例肺腺癌恶性胸腔积液患者随机分为恩度联合顺铂组、恩度组和顺铂组,具体方法:恩度30mg/次,顺铂30mg/次,每两天一次,连续3次为1疗程,最多可连续接受2疗程治疗。评估三组的近期疗效、生活质量(QOL)和不良反应。结果恩度联合顺铂组有效率、QOL改善率分别为83.3%、76.7%,恩度组53.3%、63.3%,顺铂组50%、60%。恩度联合顺铂组有效率高于恩度组、顺铂组,组间差异有统计学意义(P=0.014)。三组QOL改善率差异无统计学意义。恩度联合顺铂组、顺铂组不良反应发生率比较差异无统计学意义,恩度组低于上述两组,差异具统计学意义(P0.017)。结论恩度联合顺铂胸腔内注射治疗肺腺癌胸腔积液可明显提高缓解率,改善生活质量,且不良反应小,具有较好的临床疗效及用药安全性。     

Carrelizumab combined with anlotinib in the treatment of extensive-stage small cell lung cancer: A case report

Rationale:The emergence of immune checkpoint inhibitors has brought new breakthroughs in the treatment of small cell lung cancer (SCLC). Programmed cell death-ligand 1 inhibitors combined with chemotherapy have been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). However, programmed death 1 inhibitors have limited efficacy in the treatment of SCLC. The reason may be related to the abnormal vascular state in the tumor microenvironment.Patient concerns:A 55-year-old male patient, presenting cough and sputum for 1 month.Diagnoses:The patient was clinically diagnosed with SCLC and staged as ES-SCLC.Interventions:Etoposide combined with lobaplatin treatment every 3 weeks for 4 cycles, evaluate as progressive disease. On the basis of the original plan, combined with camrelizumab for 2 cycles, evaluation as progressive disease. Then, the patient was treated with intravenous infusion of camrelizumab plus oral anlotinib. After 4 cycles, evaluation as partial response. Then we continued to use camrelizumab combined with anlotinib treatment for the patient. At the end of 26 cycles, the chest computed tomography examination revealed that the patient had achieved complete remission.Outcomes:After treated with carrelizumab combined with anlotinib for 26 cycles, the curative effect was evaluated as complete remission, progression-free survival was 24 months and there was no immune-related adverse reaction during treatment period. Besides, the patient developed complicated hand–foot syndrome, but this symptom was significantly relieved after reducing the dosage of anlotinib.Lessons:In this case, antiangiogenesis combined with programmed death 1 inhibitors significantly inhibited tumor progression. It also indicated that anlotinib concurrent carrelizumab may be a superior choice for ES-SCLC. Further clinical trials required to confifirm its effificacy and safety.     

Long-term response with low-dose of apatinib combined with S-1 in pretreated patient with advanced squamous cell lung cancer: A case report

Rationale:Squamous cell lung cancer is one of the major pathological types in patients with non-small cell lung cancer. Since treatment with angiogenic agents and target drugs in patients with advanced squamous cell lung cancer is not promising, there are limited strategies to improve the outcome in such patients. Herein, we report a pretreated patient with advanced squamous cell lung cancer, who received low-dose of apatinib combined with S-1 as salvage treatment, with good long-term response.Patient concerns:The patient complained of dry cough for one month without any relief by medication. Otherwise, she denied any other medical or family history.Diagnosis:According to the chest computed tomography, and pathologic findings from biopsy for lesion in lung, the patient was diagnosed with lung squamous cell lung cancer with enlargement of bilateral supraclavicular lymph nodes suggesting metastasis, staged as IIIb.Interventions:The patient received gemcitabine plus cisplatin as first line treatment, and gemcitabine as maintenance therapy. After progression, she received vinorelbine as second line treatment. After progression again, she received low-dose apatinib combined with S-1 as third line treatment.Outcomes:With the follow-up period from October 21, 2014, to April 6, 2019, there were 15 months, 9 months, and 24 months of progression-free survival time for first line (including maintenance therapy), second line, and third line treatment, respectively. The only adverse event was neutropenia at grade 2 (CTC AE) occurring during the maintenance treatment.Lessons:This case indicated that low-dose apatinib combined with S-1 might be effective and safe in selected pretreated patients with advanced squamous cell lung cancer. It might be worthy to conduct further researches to investigate the efficacy and safety of the combination therapy in such patients.     

吉西他滨联合顺铂对晚期肺鳞癌及肺腺癌治疗的临床疗效比较

目的观察吉西他滨联合顺铂的化疗方案对晚期肺鳞癌及肺腺癌的临床疗效及生存差异。方法肺鳞癌组47例及肺腺癌37例患者给予吉西他滨（1000mg／m2）联合顺铂（75mg／m。）化疗,每21天为一周期,共化疗4个周期。结果肺鳞癌组PR为14例（29．8％）,SD为21例（44．7％）,PD为12例（25．5％）,RR为29．8％,中位生存期为13个月,1年生存率为53．2％;肺腺癌组PR为10例（27．0％）,SD为18例（48．6％）,PD为9例（24．3％）,RR为27．0％,中位生存期为9个月,1年生存率为27．0％;结论吉西他滨联合顺铂对晚期肺癌及鳞癌的临床疗效相当,但肺鳞癌较肺腺癌具有较好的1年生存率及生存时间。     

Sintilimab induced diabetic ketoacidosis in a patient with small cell lung cancer: A case report and literature review

Rationale:Sintilimab is a novel programmed cell death receptor-1 (PD-1) inhibitor approved in the treatment of classical Hodgkin''s lymphoma and undergoing clinical trials for various malignancies. As a PD-1 inhibitor, sintilimab is known to cause autoimmune adverse events similar to other PD-1 inhibitors. Diabetic ketoacidosis (DKA) is a rare but severe adverse event of this therapy.Patient concerns:We report a case of a 59-year-old man who developed DKA after 5 doses of sintilimab for small cell lung cancer. His fasting glycemia level was 14.07 mmol/L, urine ketone bodies were 4+, arterial blood pH was 7.271, bicarbonate was 12.3 mmol/L, and glycated hemoglobin (HbA1c) was 7.4%. Extended investigations revealed that fasting C-peptide was undetectable (<0.003 nmol/L).Diagnosis:These laboratory investigations supported the diagnosis of fulminant type 1 diabetes mellitus, but no β-cell related antibodies were positive.Interventions:After remission of DKA, he was treated with insulin therapy to acquire a normalization of glycemia and the disappearance of symptoms.Outcomes:Sintilimab was withheld after 6 cycles and was converted to durvalumab to sustain the therapeutic effect.Lessons:This case and associated literature review illustrate the importance of educating and monitoring patients who start PD-1 inhibitor therapy regarding this potentially life-threatening complication.     

Sustained remission of multi-line relapsed extranodal NK/T-cell lymphoma,nasal type,following sintilimab and chidamide: A case report

Introduction:There is currently no optimal treatment modality for refractory or relapsed Extranodal NK/T-cell lymphoma, nasal type (ENKTL). In recent years, programmed cell death protein 1 (PD-1)/programmed cell – ligand 1 pathway blockade and histone deacetylase inhibitors have emerged as promising strategies for refractory or relapsed ENKTL. Accumulating evidence has shown that therapeutic effects of anti-PD-1 antibody could be enhanced by histone deacetylase inhibitors.Patient Concerns:A 52-year-old male patient was diagnosed with stage I ENKTL by biopsy on February 2010.Diagnosis:positron emission tomography–computed tomography (PET-CT) and biopsy were used to diagnose relapsed ENKTL in 2014.Interventions:The patient was treated with radiotherapy and six cycles of etoposide, prednisone, vincristine (Oncovin), cyclophosphamide and doxorubicin hydrochloride and achieved complete remission (CR) by PET-CT in August 2010. In November 2014, the patient was diagnosed with relapsed stage IV ENKTL and was treated with six cycles of alternative chemotherapy with the regimen of steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide and pegaspargase plus Gemcitabine, Oxaliplatin along with radiotherapy. The patient achieved remission and was placed on thalidomide maintenance treatment. Upon suspicion of relapse suggested by PET-CT, Autologous stem cell transplant was performed after BCNU, etoposide, Ara-C, and melphalan preconditioning on February 2016. Following relapse again in December 2016, the lesions of left femur were treated with radiotherapy and he received anti-PD-1 antibody. He was treated with 4 cycles of pegaspargase plus Gemcitabine, Oxaliplatin on August 2017. The patient''s condition improved. He received maintenance and consolidation therapy including lenalidomide, radiotherapy of the right nasal cavity and paranasal sinuses and antigen-specific reactive T cell infusions. PET-CT imaging showed there was high metabolic activity signal in the distal end of right femoral on August 2018 and the treatment regimen was adjusted to radiotherapy of the distal end of right femoral and systemic treatment of PD-1 antibody Sintilimab and chidamide 30 mg. After 5 months post-treatment, biopsy of nasopharynx showed no lymphoma cells. The patient continued the treatment of Sintilimab and chidamide 20 mg.Outcomes:PET-CT imaging showed his lesions obtained remission after 8 months post-treatment.Conclusion:Thus, combination of sintilimab and chidamide can be used to treat relapsed ENKTL following treatment failure from chemo-, radio-, and immuno-therapy. A clinical trial has been launched.     

接触蛋白-1在原发性肺鳞状细胞癌组织中的表达及临床意义

目的探讨神经细胞粘附分子-接触蛋白-1(contactin-1, CNTN-1)在原发性肺鳞状细胞癌组织中的表达,并探讨其表达与患者临床病理参数之间的关系。 方法收集63例原发性肺鳞状细胞癌手术石蜡切片标本和20例正常肺上皮组织标本,采用免疫组织化学染色技术检测CNTN-1表达,并分析其与患者临床病理参数之间的关系。 结果63例原发性肺鳞癌组织标本中,阳性表达35例,阴性表达26例,2例因石蜡切片上的标本脱落而无癌组织,CNTN-1在人正常肺泡上皮组织中不表达,在原发性肺鳞状细胞癌组织中广泛表达,阳性率为55.56%(35/63);χ²检验或Fisher精确概率法检验结果显示,CNTN-1阳性表达与患者吸烟和术前淋巴结侵袭显著相关(P<0.05),而CNTN-1差异表达与患者各临床病理参数之间无相关性。 结论CNTN-1是一个潜在的原发性肺鳞状细胞癌患者预后的生物学标志物。     

Prediction of lung squamous cell carcinoma immune microenvironment and immunotherapy efficiency with pyroptosis-derived genes

Lung squamous cell carcinoma (LUSC) is a common subtype of lung cancer that exhibits diverse pyroptosis regulatory patterns. Studies have highlighted the significance of pyroptosis in cancer invasion and immune responses. We aimed to explore the signatures of pyroptosis-related genes and their immune relevance in LUSC. Using The Cancer Genome Atlas (TCGA)-LUSC cohort and 5 gene expression omnibus (GEO) datasets, we performed consensus clustering based on 41 pyroptosis-related genes, and single sample gene set enrichment analysis (ssGSEA) was employed to calculate the infiltration levels of distinct clusters. A pyroptosis scoring scheme using the principal component analysis (PCA) method was used to quantify pyroptosis regulation in patients with LUSC and predict their prognosis. Four pyroptosis clusters were identified among 833 LUSC samples, which were associated with different Kyoto encyclopedia of genes and genome (KEGG) signaling pathways and tumor microenvironment infiltration features, and were highly consistent with 4 reported immune phenotypes: immune-responsive, immune-non-functional, immune-exclusion, and immune-ignorance. We then divided the patients into high- and low-pyroptosis score subgroups, and patients with higher scores were characterized by prolonged survival and attenuated immune infiltration. Moreover, higher scores were correlated with male patients, higher microsatellite instability, lower immune checkpoint inhibitor expression (such as CTLA-4 and GAL-9), and high mutation rates of typical mutated genes (e.g., TP53 and TTN). In particular, patients with lower pyroptosis scores showed better immune response to immune checkpoint inhibitor treatment. Pyroptosis regulatory patterns in the immune microenvironment can predict the clinical outcomes of patients with LUSC. Accurately quantifying the pyroptosis of individual patients will strengthen the understanding of heterogeneity within the LUSC tumor microenvironment infiltration areas.     

PD-1 inhibitor toripalimab with gemcitabine as a neoadjuvant therapy for muscle-invasive bladder urothelial carcinoma: A case report

Rationale:Routine neoadjuvant therapy for muscle-invasive bladder urothelial carcinoma prior to radical surgery is curative. With the increase in cancer immunotherapy, neoadjuvant immunotherapy has been used as an important complement to neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma. Toripalimab is a recombinant, humanized IgG4 monoclonal antibody directed against programmed cell death protein 1 and received the first global approval for the treatment of unresectable or metastatic melanoma in China on December 17, 2018.Patient concerns and diagnosis:A 57-year-old man was admitted to our hospital because of hematuria for 1 week. The patient was diagnosed pathologically with muscle-invasive bladder urothelial carcinoma.Interventions and outcomes:The patient received neoadjuvant toripalimab combined with gemcitabine therapy. The patient showed partial response. Subsequently, radical cystectomy was performed.Lessons:Toripalimab combined with gemcitabine exhibited accurate antitumor activity and may be a promising novel neoadjuvant therapy for muscle-invasive urothelial carcinoma.     

Monitoring disease progression and treatment efficacy with circulating tumor cells in esophageal squamous cell carcinoma: A case report

This study investigated whether changes in circulating tumor cell (CTC) numbers reflect tumor progression and treatment efficacy in esophageal squamous cell carcinoma (ESCC). A 47-year-old male patient with ESCC is presented in this case study. The patient was evaluated for a series of serum tumor markers and subjected to radiological examinations before and after surgery and during follow-up over the course of five years. In addition, the CTCs in 7.5 mL of peripheral blood were enriched by magnetic-activated cell sorting negative selection and identified by immunofluorescence staining. Serum tumor markers remained within normal ranges and were discordant with imaging scans during the follow-up. Initially, one CTC was detected in the peripheral blood sample, and 14 were observed seven days after the operation. After 12 wk, subcutaneous metastases and bone metastases occurred, and the number of CTCs increased to 84. After 48 wk, lung metastases were noted, and the CTC level was 21. At 104 wk, the number of CTCs was 14, and disease recurrence was detected by positron emission tomography-computed tomography. The CTC counts were in accord with the imaging studies at several time points. The additional information provided by CTC enumeration could thus facilitate monitoring of disease status and treatment efficacy and provide support for treatment decisions.     

吉西他滨联合奈达铂序贯化放疗治疗肺鳞癌74例临床分析

目的：探讨吉西他滨联合奈达铂序贯化放疗治疗肺鳞癌的临床应用。方法74例入选肺鳞癌患者随机分为实验组(n =37)和对照组(n =37)。对照组采用吉西他滨联合奈达铂化疗;实验组在化疗基础上采用三维适形放疗,化疗方案以21 d 为1个周期,接受4个周期化疗,化疗的第1周期同期对原发病灶进行三维适形放疗。观察患者近期临床疗效、生活质量改善情况及不良反应。结果2组患者全部完成治疗计划,实验组有效率为54.1%,疾病控制率为81.1%,疗效优于对照组(P <0.05)。实验组、对照组生活质量改善有效率为分别为73.0%、64.9%,组间比较差异无统计学意义(P >0.05)。2组主要不良反应为白细胞、血小板、血红蛋白下降及恶心呕吐,实验组患者放射性肺炎、放射性食管炎程度较轻,经对症处理后均可耐受。结论吉西他滨联合奈达铂序贯化放疗治疗肺鳞癌临床疗效显著,不良反应较轻,值得临床深入研究及推广应用。     

Efficacy and safety of pembrolizumab monotherapy in EGFR-mutant squamous cell lung cancer with PD-L1 over-expression: A case report

Background:Epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) patients are less likely to be programmed death-ligand 1 (PD-L1)-positive compared with wild-type EGFR mutant tumors. Given the rarity of actionable driver genes in squamous cell lung cancer (SQCC), the frequency of SQCC patients simultaneously carrying EGFR driver gene mutation and having PD-L1 over-expression is extremely low. Studies on the effectiveness and safety of EGFR-TKIs or immune-checkpoint inhibitors (ICIs) in this subset of patients are lacking.Patient concerns:The patient suffered from coughing and chest pain for 1 month. A chest CT revealed a mass with a cavity in the right lung, enlarged mediastinal lymph nodes, diffuse pleural thickening in the right pleura, and pleural effusion of the right chest.Diagnosis:A pleural biopsy was performed using a video-assisted thoracoscope. The pathological examination revealed a poorly differentiated squamous cell carcinoma of lung. Further genetic testing identified exon 19 deletion mutation in EGFR with abundance of 0.27%. Meanwhile, immunohistochemical PD-L1 analysis showed a TPS of 90%.Interventions:The patient was initially resistant to EGFR-TKIs but exhibited a rapid and marked response to pembrolizumab.Outcomes:After 5 cycles of pembrolizumab monotherapy, the patient developed Grade 3 immune-related dermatitis, and ICI therapy was suspended.Conclusions:ICI monotherapy could be an effective therapy in SQCC patients with low-abundance of EGFR mutations and PD-L1 over-expression. However, close attention should be paid to immune-related adverse events.     

重组人p53腺病毒联合顺铂治疗NSCLC合并胸腔积液临床研究

目的本研究评价重组人p53腺病毒注射液（rAd-p53）联合顺铂治疗肺癌所致胸腔积液的临床疗效和毒副反应。方法将38例非小细胞肺癌（NSCLC）合并胸腔积液患者随机分为治疗组和对照组两组。所有患者均在第1、8 d应用吉西他滨1.0 g/m2静脉点滴,每3周重复1次。在上述治疗基础上,治疗组胸腔内注入rAd-p53 1×10^12 VP和顺铂30 mg/m2每次;对照组仅胸腔内注入顺铂30 mg/m2每次,两组均每周重复1次,连用4次后观察疗效。结果治疗组和对照组的有效率分别为80.95%和47.06%（P〈0.05）;治疗组和对照组的一般状况改善率分别为66.67%和29.41%（P〈0.05）;两组患者主要不良反应均为发热、胸痛、消化道反应及白细胞减少,治疗组发热的发生率高于对照组（P〈0.05）,主要为自限性,36 h后一般都能自行恢复。结论重组人p53腺病毒注射液联合顺铂治疗肺癌所致胸腔积液疗效确切,安全,值得临床推广使用。     

Remarkable response to anti-PD1 immunotherapy in refractory metastatic high-grade myxofibrosarcoma patient: A case report

Introduction:Myxofibrosarcoma (MFS) is a locally aggressive tumor and has the potential to be fatal because of distant metastasis. Immunotherapy targeting either programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) has recently shown a curative effect on multiple cancers including melanoma, non-small cell lung cancer, and renal cell carcinoma. Although the immunotherapy has been applied in sarcoma, there is little information about the efficiency to treat metastatic MFS.Patient concerns:A 42-year-old male presented to the clinic with a mass in the left thigh. Mass resection and ligament replacement surgery were performed.Diagnoses:The patient was diagnosed as high-grade MFS (federation nationale des centres de lutte contre le cancer, Grade 3) with pulmonary metastasis.Interventions:In the past few years, he was treated with surgery, chemoradiotherapy, and Anlotinib (an angiogenesis inhibitor), but the metastatic lesion continued to progress. About 40% to 50% of tumor cells in his pulmonary tissues were showed positive PD-L1 expression and his tumor mutational burden was 215Muts. Thus, he received Camrelizumab (PD-1 inhibitor).Outcomes:Six months after the initiating immunotherapy of Camrelizumab, the size of pulmonary lesions showed marked shrinkage, indicating a partial response. After a follow-up of 18 months, the patient remained in good condition without progressive disease.Conclusion:This case described here demonstrated that immunotherapy of PD-1 inhibitor is a promising treatment option for refractory MFS with PD-L1 positive or tumor mutational burden -high, which could contribute to effective tumor response.     

Precise medicine of programmed cell death-1/programmed cell death 1 ligand 1 inhibitor immunotherapy combined radiotherapy for inoperable advanced lung cancer: A protocol for systematic review and meta-analysis

Background:Programmed cell death-1/programmed cell death 1 ligand 1 (PD-1/PD-L1) inhibitors are a group of immune checkpoint inhibitors immunotherapy for cancer treatment. These immune checkpoint inhibitors are becoming first-line treatments for several types of cancer. Radiotherapy for cancer is a traditional treatment and the therapeutic effect is not satisfactory due to the side effect of chemotherapeutic drugs. This study aims to evaluate the efficacy and safety of PD1/PD-L1 inhibitor immunotherapy combined chemotherapy for inoperable advanced lung cancer.Methods:We will utilize PubMed, PubMed Central, EMbase, Medline, CNKI, WAN FANG Database, and Web of Science to screen eligible studies published from January 1, 2015 to December 30, 2020. Two reviewers will extract data and evaluate the risk of bias independently. The quality of the included studies will be evaluated using the RevMan 5.3 software for data analysis.Results:This review will summarize high-quality evidence of trials to evaluate the precise medicine efficacy and safety of PD1/PD-L1 inhibitor combined radiotherapy for inoperable advanced lung cancer.Conclusions:The findings of the systematic review will provide scientific evidence of the efficacy and safety of PD1/PD-L1 inhibitor combined radiotherapy for inoperable advanced lung cancer to guide the clinician''s drug use.Ethics and dissemination:Not applicable.INPLASY registration number:INPLASY202140123.     

Solitary pancreatic metastasis from squamous cell lung carcinoma: A case report and review of literature

BACKGROUNDPancreatic metastases from squamous cell lung carcinoma (SCLC) are unusual. These lesions are often asymptomatic and detected incidentally or during follow-up investigations, occasionally several years after removal of the primary tumor.CASE SUMMARYA 56-year-old male with SCLC developed jaundice 1 mo after the cancer diagnosis. An abdominal computed tomography (CT) scan showed a mass in the pancreatic head with distention of both intra- and extrahepatic biliary ducts. Endoscopic retrograde cholangiopancreatography and sphincterotomy were performed first, culminating with plastic biliary stent placement. Cytological examination of the pancreatic mass sample collected by fine-needle aspiration (FNA) under endoscopic ultrasound (EUS) guidance revealed the presence of malignant cells compatible with well-differentiated squamous cell carcinoma. After liver function normalized, chemotherapy was initiated with carboplatin and paclitaxel; however, 4 d later, the patient presented dysphagia. Cervico-thoraco-abdominal CT showed tracheoesophageal fistula and stent migration. After replacement with a 10 cm/10 mm uncovered metallic biliary stent and treatment of the tracheoesophageal fistula with a fully covered esophageal stent, the patient was able to start oral feeding progressively. He died 9 mo after the initial diagnosis.CONCLUSIONThe diagnosis of pancreatic metastasis from SCLC is challenging for clinicians. EUS-FNA is the primary exam for confirmatory diagnosis.     

肺鳞癌结肠黏膜转移一例报告和文献复习

肺癌患者发生结肠转移非常罕见，患者一般无典型症状，晚期可出现腹痛、消化道出血、梗阻、穿孔等症状，并发症和死亡率较高，短期预后差。本中心报道一位63岁男性患者，以"间断咳嗽和右下腹隐痛"就诊，诊断肺鳞状细胞癌并纵隔淋巴结转移和结肠寡转移，经过PD-1免疫治疗，症状改善明显，目前仍在治疗和随访中。     

Activation of the BMP-BMPR pathway conferred resistance to EGFR-TKIs in lung squamous cell carcinoma patients with EGFR mutations

The empirical criteria for defining a clinical subtype of lung cancer are gradually transiting from histopathology to genetic variations in driver genes. Targeting these driver mutations, such as sensitizing epidermal growth factor receptor (EGFR) mutations, has dramatically improved the prognosis of advanced non–small cell lung cancer (NSCLC). However, the clinical benefit of molecularly targeted therapy on NSCLC appears to be different between lung adenocarcinomas and squamous cell carcinomas (SqCCs). We report here that the resistance of lung SqCC harboring EGFR mutations to EGFR tyrosine kinase inhibitors (EGFR-TKIs) was due to the activation of BMP-BMPR-Smad1/5-p70S6K. The combined treatment of these tumor cells with EGFR-TKI, together with inhibitors specific to BMPR or downstream mTOR, effectively reversed the resistance to EGFR-TKI. Moreover, blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC. This study details the empirical basis for a feasible clinical solution for squamous cell carcinomas with EGFR mutations.Traditionally, the classification of lung cancer has been based primarily on histology and morphology (1, 2). With the identification of mutated driver oncogenes, methods from molecular pathology are gradually transforming the definition of the various types of lung cancers (3). Targeting gene aberrances such as epidermal growth factor receptor (EGFR) mutations (4–8) and anaplastic lymphoma kinase (ALK) fusion (9, 10) has significantly improved the prognosis of advanced non–small cell lung cancer (NSCLC). However, the clinical benefits brought by targeted therapies are mainly limited to nonsquamous NSCLC (11), while chemotherapy remains the major therapeutic choice for squamous cell carcinomas (SqCCs).Recent studies assessing somatic mutations and copy number alteration (CNA) profiles in SqCC performed by the Cancer Genome Atlas project and other investigators have disclosed specific gene mutations, including GRM8, BAI3, ERBB4, RUNX1T1, KEAP1, and FBXW7, and CNAs in 3q26, 24, 27, 32–34, and 8p12.35 in lung SqCC (12, 13). About half of all patients with lung SqCC carry multiple gene aberrances, indicating that complex genomic characterizations are more common in lung SqCC than in adenocarcinoma (ADC). Thus, successful therapeutic strategies that target a single driver gene in lung ADC might not be feasible for lung SqCC patients.Targeting EGFR mutations by EGFR tyrosine kinase inhibitors (TKIs) is one of the successful strategies in treating lung ADC. EGFR-TKIs obtained median progression-free survival (PFS) of 10–13 mo in EGFR-mutated lung ADC, but only ∼3 mo in lung SqCC with EGFR mutations (11, 14). Moreover, whether EGFR mutations exist in lung SqCC still remains controversial. There is a belief that EGFR mutations might not even occur in pure pulmonary SqCC, and that the occasional detection of these mutations in samples diagnosed as SqCC was due to mixed adenosquamous carcinoma and poorly differentiated ADC (15, 16). In current clinical practice, the utilization of EGFR-TKIs and the assessment of EGFR mutations are still routinely performed in lung SqCC, especially in nonsmokers. Therefore, it is critical to identify the subgroups of lung SqCC patients that are suitable for EGFR-TKI treatment. Exploring the mechanism of resistance to EGFR-TKIs in lung SqCC will deepen our understanding of the differences in tumorigenic profiling between lung SqCC and ADC, and should contribute to guiding clinical therapeutic decisions.In the present study, we demonstrated that lung SqCC patients with EGFR mutations indeed represent a subset of NSCLC. We further showed that lung SqCC cell lines were resistant to EGFR-TKIs both in vitro and in vivo. We also investigated the mechanisms of resistance to EGFR-TKI in this subset of patients and provided potential strategies for overcoming TKI resistance in these patients.     

Metastases to duodenum in cervical squamous cell carcinoma: A case report and review of the literature

Rationale:Metastases to the duodenum in cervical squamous cell carcinoma are extremely rare, with only 7 cases reported in the published English literature.Patient concerns:We present the case of a 66-year-old woman with duodenal metastasis of cervical squamous cell carcinoma who presented with nausea and vomiting within the past 12 days.Diagnosis:Esophagogastroduodenoscopy revealed a circular narrowed 2nd part of the duodenum with congested and edematous mucosa, which was biopsied for a suspected neoplastic lesion. The pathological diagnosis indicated squamous cell carcinoma identical to the original tumor, confirming duodenal metastasis.Interventions:The patient received total parenteral nutrition on admission, but symptoms of jaundice soon appeared in the following week, suggesting infiltration of carcinoma into the common bile duct. After percutaneous transhepatic cholangial drainage was performed, jaundice eased in the following 3 days, and an uncovered self-expandable metallic stent was subsequently inserted into the stenosis of 2nd and 3rd part of the duodenum. Subsequently, the patient''s diet quickly resumed.Outcomes:The patient refused further intervention and was discharged home to continue palliative care at the local hospital.Lessons:Clinicians should be alert to patients’ past medical history to ensure that duodenal metastasis of other tumors is considered in the differential diagnosis. For endoscopists, awareness of such patterns of duodenal stenosis is vital for the accurate recognition of such infrequent diseases.