Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations

Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%-20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.

Diaphragmatic fenestration an effective treatment for refractory postoperative chylothorax: a case report

Postoperative chylothorax remains a clinical challenge to the surgeon with substantial morbidity and risk of mortality. Though an uncommon complication, it is known to complicate cardiac and non-cardiac thoracic surgeries. Conservative measures are first employed in managing this. Surgical options are adopted when the effusion is protracted, most recent of which includes diaphragmatic fenestration. A 9-year-old girl is presented who developed recurrent right chylothorax following thoracoscopic excision of a cystic lymphangioma. Following failed conservative therapy, she had thoracic duct ligation and right diaphragmatic fenestration (using fenestrated polytetrafluoroethylene patch) with satisfactory outcome. Aetio-pathologic mechanisms implicated in postoperative chylothorax have been classified into traumatic (iatrogenic injury to the thoracic duct or its branches) and non-traumatic. With initial conservative measures (repeated pleural aspirations and intercostal drainage, medium chain triglyceride/ low fat feeds or alternatively, fasting and total parenteral nutrition) spontaneous closure remains unpredictable. Diaphragmatic fenestration when employed resulted in faster resolution of effusion and earlier commencement of enteral feeding with no significant complication. Diaphragmatic fenestration is effective and safe for treating refractory post-operative chylothorax.

A Rare Case of Haemophilus parahaemolyticus Pneumonia

@#Pneumonia is a common lung infection. Common bacterial cause of this serious lung infection includes Streptococcus pneumoniae, Haemophilus influenzae and Mycoplasma pneumoniae. Haemophilus parahaemolyticus pneumonia is an uncommon cause of bacterial pneumonia, occurring mainly as an opportunistic pathogen in immunocompromised patients as in this case, diabetes mellitus. Therefore, this case report will look at a case of 49-year-old man who was diagnosed with this uncommon pathogen which was successfully eradicated with antibiotics. This case report will look at a case of 49 years old who was diagnosed with this uncommon pathogen which was successfully eradicated with antibiotics.

Sebaceous carcinoma of the hand: an extremely rare case

Sebaceous carcinoma is an aggressive tumor derived from adnexal epithelium of sebaceous gland and accounts for 1% of all cutaneous malignancy. Most commonly found at head and neck region. with sebaceous carcinoma in extrimity few than 100 cases have been formally documented. Since this lesion are uncommon, this lession tend to be misdiagnosed. Sebaceous carcinoma is a clinically innocuous appearing lesion with no pathognomonic features. Diagnosis is seldom made before operation and frequently misdiagnosed after operation We present our experienced with sebaceous carcinoma. female 45 years old, with history mass at her left hand grew rapidly during the past 4 months. At the beginning, there was a small wart over the little finger of her left hand that was not changing for the past 30 years. The patient then started scratching the wart until it fell off (1 year ago). The wound initially healed but then the same lesion grew back and became even larger. The patient repeated this habit and the lesion grew into its current size. The lesion itself started to bleed easily and became infected. During the past 4 months, patient also experienced the same lesion growing at her left index finger. Patient also complaint of pain which was localized to the lesion, non-radiating, and was felt increased when the patient scratched at the lesion. We performed resection of tumor and amputation at 4th and 5th fingers and also disarticulation at MCP joint 2nd finger and take a sample as histhopatological examination.

A Review of EGFR-TKIs Therapy of Non-small Cell Lung Cancer with Uncommon EGFR Mutations / 中国肺癌杂志

Lung cancer is the most common cancer and the leading cause of cancer death. Non-small cell lung cancer (NSCLC) represents over 85% of all lung cancers, and up to 50% of Asian NSCLC patients harboring epidermal growth factor receptor (EGFR) gene mutations. A number of studies have consistently demonstrated that uncommon EGFR-mutated NSCLC patients treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can achieve better survival outcomes. However, because uncommon EGFR mutations are generally associated with reduced sensitivity to EGFR-TKIs, which will bring a negative impact on the result of the study, the majority of clinical trials investigating the efficacy of EGFR-TKIs have included only patients with common EGFR mutations. In addition, uncommon EGFR mutations are rare in themselves, leading to the small number of such patients enrolled in these trials. Due to the small number and highly heterogeneous sensitivity of uncommon EGFR mutations, the efficacy of EGFR-TKIs in patients harboring uncommon EGFR mutations remains elusive. This article reviews the efficacy of EGFR-TKIs in patients with uncommon EGFR mutations, and give some reasonable advice about the selection of treatments for patients with NSCLC who harbor uncommon EGFR mutations.

Efficacy of first generation EGFR-TKIs and chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations / 中华肿瘤杂志

Objective@#To investigate the clinical effects of first generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) compared with platinum-based chemotherapy as first-line therapy in advanced lung adenocarcinoma patients with uncommon EGFR mutations.@*Methods@#Clinical data of 4 276 patients diagnosed as advanced lung adenocarcinoma (ⅢB/Ⅳ) underwent EGFR gene detection at the Affiliated Cancer Hospital of Zhengzhou University from January 2012 to February 2018 were collected and 99 cases with uncommon EGFR mutations were selected. The clinical pathological features, treatment outcomes, treatment options and prognosis after first-line treatment of the 99 cases were analysed and compared with other patients with common EGFR mutations.@*Results@#The objective response rates of patients with uncommon EGFR mutations receiving EGFR-TKIs or platinum-based chemotherapy were 33.0% and 27.1%, respectively. The disease control rates were 76.5% and 87.5%, respectively. The progression-free survival (PFS) of patients treated with EGFR-TKIs was 7.2 months, significantly superior than 4.9 months of patients receiving chemotherapy (P=0.009). The overall survival of patients treated with EGFR-TKIs was 14.3 months, significantly worse than 20.7 months of patients receiving chemotherapy (P=0.034). Multivariate analysis showed that distant metastases (P=0.001) and smoking history (P=0.013) were independent prognostic factors for OS of lung adenocarcinoma patients with EGFR uncommon mutations.@*Conclusions@#Compared with chemotherapy, the usage of first generation of EGFR-TKIs as first-line therapy can improve the short-term efficacy of advanced lung adenocarcinoma patients with EGFR uncommon mutations. However, platinum-based chemotherapy shows a longer overall survival.

New exploration on clinical treatment of injuries caused by uncommon agents or in extraordinary regions / 中华烧伤杂志

Burns caused by uncommon agents means those caused by other agents except heating power, with special characteristics existing in traumatogenesis, pathophysiology, and clinical manifestation. With the development of social economy, various new techniques and new equipments are springing up. In the practical use, improper operations would become traumatogenic agents and cause various special types of trauma. In addition, some special injuries emerged with the changes in people′s lifestyle. For battle injury, some new war wounds, which are different from fire-arm injuries in the past, appeared with the emergence of acoustic wave, light wave, electrical and magnetic weapons. Extraordinary regions are those located on body surface with anatomic and physiological particularity. Injuries caused by uncommon traumatogenic agent or in extraordinary region are different from those ordinary burns and trauma, and their clinical treatments have special characteristics. Clinical treatments were studied aiming at these special characteristics, and some achievements in treatment of high-voltage electrical burn, hydrofluoric acid burn, wounds on special regions, and new types of burns and trauma have been made. However, a doctor′s duty is not only to cure the diseases and save the patients′ lives, but also to prevent the diseases. The suitable treatment and precautionary measures for the new types of burns and trauma that differ from ordinary burns and trauma in the past remain to be explored.

Efficacy of EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer patients with uncommon EGFR 21L861Q mutation / 上海交通大学学报（医学版）

Objective· To evaluate the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) in non small cell lung cancer (NSCLC)patients with uncommon EGFR 21L861Q mutation. Methods·Between June 2011 and Marth 2015,clinical data of 21 stageⅢB/ⅣNSCLC patients who received EGFR-TKI harboring uncommon 21L861Q mutation in EGFR at the Shanghai Chest Hospital were collected.Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS ) and overall survival (OS ) of the patients under TKI therapy were retrospectively analyzed. Results · ORR and DCR of the patients under TKIs therapy (first-line+second-line+third-line) were 42.9% and 66.7% respectively. PFS and OS of patients who received therapy that consisted of EGFR-TKIs(first-line+second-line+third-line)were 7.03 months(95% CI,5.50-8.69)and 22.80 months(95% CI,16.22-25.65). Conclusion·Our post-hoc analyses demonstrated that EGFR-TKIs showed activity in patients with uncommon EGFR 21L861Q-mutant NSCLC, less effective than in those with common mutations.

Clinicopathologic characteristics of non-small cell lung cancer patients with seldom mutation types of epidermal growth factor receptor and treatment analysis / 中国肿瘤临床

Objective:To compare clinicopathologic parameters of uncommon mutations of epidermal growth factor receptor (EGFR) and preliminary therapeutic effects of EGFR-TKI treatment in patients with non-small cell lung cancer. Methods:We collected clinico-pathological data from 29 patients with non-small cell lung cancer who carry uncommon mutations of EGFR, which were pathological-ly confirmed in the Tumor Hospital Affiliated to Xinjiang Medical University, from January 2012 to April 2016. Then we analyzed the re-lationship between the clinicopathologic characteristics of uncommon mutations and therapeutic effects of EGFR-TKIs. Results:Among the 29 cases of patients with uncommon mutations, the most common distant metastasis organs were ipsilateral/contralateral lung tissue, bone, brain, liver, and adrenal gland;the most common metastatic lymph nodes were hilar lymph node, supraclavicular/subclavian lymph node, neck-root lymph node, and mediastinal lymph node. In seldom mutations, 16 cases of single mutation were found:5 cases of L861Q, 5 cases of G719X, 4 cases of 20ins, and 2 cases of S768I. By contrast, 11 cases of double mutations were found:4 cases of S768I and 20ins, 1 case of double mutation of L858R and S768I, 1 case of double mutation of 19Del and T790M, 2 cases of double mutations of L861Q and G719X, 1 case of 19Del and S768I, 1 case of 20ins and G719X, and 1 case of T790M and G719X. Moreover, 2 cases of triple mutation were found:1 case of L858R, L861Q, and G719X;1 case of S768I, 20ins, and G719X. The objective response rate (ORR) of the first-line EGFR-TKI therapy was 43.75%, the disease control rate (DCR) was 50%, and the median progression-free survival (mPFS) was 5.5 months. Furthermore, the ORR of the second-line EGFR-TKI therapy was 28.57%, the DCR was 42.85%, and the mPFS was 4 months. Moreover, the ORR of the third-line EGFR-TKI therapy was 33.33%, the DCR was 50.00%, and the mPFS was 2.67 months. Conclusion:Great individual differences were found on EGFR uncommon mutations for effective rate and sur-vival time of EGFR-TKI treatment;in general, ORR and mPFS of EGFR seldom mutations were lower than classical mutations and partly higher than wild types. The first-line therapeutic effects of EGFR-TKI therapy was slightly better than the second-line or third-line thera-peutic effects;however, no significant statistical difference was observed .

A rare case of multifocal pseudomyogenic hemangioendothelioma, involving soft tissues and bone, misdiagnosed as a rhabdomyosarcoma: Diagnostic and treatment implications.

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon, but distinctive soft tissue tumor, characterized by multifocality. A 17‑year‑old male referred to us with progressively increasing multiple subcutaneous nodular lesions over his left leg and foot, reported elsewhere as a spindle cell rhabdomyosarcoma. On review, microscopy showed a cellular tumor comprising plump spindle cells arranged in loose fascicles with interspersed inflammatory cells. Tumor cells exhibited mild nuclear variation. Immunohistochemically, tumor cells expressed AE1/AE3, CD31, Fli‑1, and smooth muscle actin (SMA), confirming diagnosis of PHE. Whole‑body positron emission tomography–computed tomography (PET‑CT) scan revealed multiple, metabolically active, subcutaneous nodular lesions over the left lower leg and in the distal tibia. Subsequently, resection specimens from the various lesions and bone curettage also revealed features of PHE. Three months later, the patient developed multiple lesions over his fourth toe and left foot, for which he underwent tumor resections. At present, he is disease‑free. PHE is a locally aggressive soft tissue tumor characterized by multifocality, rarely bony involvement and can be misdiagnosed as a high‑grade sarcoma.

Impact on survival with adjuvant radiotherapy for clear cell, mucinous, and endometriod ovarian cancer: the SEER experience from 2004 to 2011 / 부인종양

OBJECTIVE: Evaluate the impact of radiotherapy on cause specific survival (CSS) and overall survival (OS) for stage (I-III) clear cell, mucinous, and endometriod ovarian cancer. METHODS: We analyzed incidence, survival, and treatments from the Surveillance, Epidemiology, and End Results (SEER) Program from 2004 to 2011 for clear cell, mucinous, and endometriod histologies of the ovary for stages (I-III). We examined CSS and OS for all three histologies combined and each histology with relation to the use of adjuvant radiation therapy (RT). Survival analysis was calculated by Kaplan-Meier and log-rank analysis. RESULTS: CSS was higher in individuals not receiving RT at 5 years (81% vs. 74%) and 10 years (74% vs. 65%, p=0.003). OS was higher in individuals not receiving RT at 5 years (76% vs. 73%) and 10 years (64% vs. 59%, p=0.039). Stage III patients receiving RT had a higher OS at 5 years (54% vs. 44%) and 10 year intervals (36% vs. 30%, p=0.037). Stage III patients with mucinous histology receiving RT had a higher OS at 5 years (50% vs. 36%) and 10 years (45% vs. 26%, p=0.052). CONCLUSION: Those receiving RT had a lower CSS and OS at 5 and 10 years. However, subgroup analysis revealed a benefit of RT in terms of OS for all stage III patients and for stage III patients with mucinous histology.

Identificação de anticorpos anti-eritrocitários de baixa frequência em paciente politransfundida com beta-talassemia: relato de caso / Identification of low frequency anti-erythrocyte antibodies in chronically transfused patient with beta-thalassemia: a case report

A taxa de aloimunização eritrocitária em pacientes politransfundidos pode atingir 50%, entretanto a frequência de anticorpos clinicamente relevantes em pacientes transfundidos não é perfeitamente conhecida, estimando-se que cerca de 1% dos pacientes são sensibilizados a cada unidade de hemácias transfundidas. O objetivo deste trabalho é relatar o caso de uma paciente de 11 anos de idade, portadora de β–talassemia major, politransfundida, na qual foi detectada, em protocolo pré-transfusional, a presença de dois anticorpos antieritrocitários raros: anti-Colton b (anti-Cob ) e anti-Lutheran 14 (anti-Lu14). Para o levantamento do histórico clínico-laboratorial da paciente, foi realizada pesquisa de prontuário arquivado no sistema de arquivos de um hospital-escola no qual a paciente é acompanhada. A fenotipagem eritrocitária em pacientes politransfudidos é essencial para minimizar os riscos de complicações devido à aloimunização e estimar a disponibilidade de sangue compatível. Assim, o relato do presente caso poderá contribuir para ampliar os conhecimentos sobre a real taxa de frequência de anticorpos anti-eritrocitários raros em paciente talassêmico.

The rate of erythrocyte alloimmunization in tranfusion-dependent patients can reach 50%, although the frequency of clinically relevant antibodies in transfused patients is not fully known, it is estimated that about 1% of patients are sensitized to each unit of transfused RBCs. The aim of this study is to report the case of an 11-year-old girl with β-thalassemia major, chronically transfused, which was detected in pre-transfusion protocol, the presence of two rare anti-erythrocyte antibodies: anti-Colton b (anti-Cob ) and anti-Lutheran 14 (anti-Lu14). To survey the clinical and laboratory patient history, research records filed in the archives of the university hospital in which the patient is monitored system was performed. The phenotyping erythrocyte in multitransfused patients is essential to decrease the risk of complications due to alloimmunization and estimate the availability of compatible blood. Thus, the report of this case may contribute to increase knowledge about of the real frequency of uncommon anti-erythrocyte antibodies in thalassemic patients.

Retroperitoneal sclerosing PEComa with melanin pigmentation and granulomatous inflammation-A rare association within an uncommon tumor.

PEComa, defined as a perivascular epithelioid cell tumor, displays a wide clinicopathological spectrum. Lately, a sclerosing PEComa has been identified as its distinct variant, but with limited documentation, in view of its rarity. Herein, we describe an uncommon case of a 53-year-old lady, who was referred to us with pain abdomen. Radiological imaging disclosed a well-defined, hypodense retroperitoneal mass. The excised tumor was a round, encapsulated soft tissue mass measuring 7 cm with a tan-brown cut surface. Microscopy showed uniform, epithelioid cells with clear cytoplasm, focal melanin pigmentation and mild nuclear atypia, arranged in sheets and nests around capillary-sized vessels in a dense sclerotic stroma. Additionally, co-existing epithelioid granulomas were noted. On immunohistochemistry (IHC), tumor cells were diffusely positive for HMB45; focally for desmin and smooth muscle actin (SMA), while negative for EMA, CD10, S100-P, Melan A, CD34, AMACR and CK MNF116. This case reinforces sclerosing PEComa as an uncommon, but a distinct clinicopathological entity and exemplifies diagnostic challenge associated with it; necessitating application of IHC markers for its correct identification. Presence of melanin pigment and granulomatous inflammation in the present tumor constitute as novel histopathological findings in a sclerosing PEComa.

Myofibroblastic sarcoma of the mandible: a case report

Myofibroblastic sarcoma is a rare tumor that mostly develops in the soft tissues of the head and neck. Within the oral cavity, a tongue lesion is the most common. A myofibroblastic sarcoma tends to recur locally instead of metastasizing. We encountered a myofibroblastic sarcoma of the mandible of a 9-year-old male and performed mass excision and additional marginal alveolectomy. So far, there is neither recurrence nor metastasis. We report this case because of the uncommon location of this tumor type and its surgical approach compared to other forms of sarcomas.

A Case of Uncommon Acquired Dermal Melanocytosis / 대한피부과학회지

Dermal melanocytosis includes a variety of congenital and acquired conditions characterized by a sparse population of intradermal dendritic, variably pigmented, spindle-shaped melanocytes. Mongolian spot, Ota's and Ito's nevi are usually present at birth or appear in early childhood. But, several types of acquired dermal melanocytosis that usually appear in adults have been reported. A 47-year-old woman presented with asymptomatic, multiple, symmetric, brownish to black colored macules on the nasal ala, both palms and both feet dorsum that had been there for 10 years. Histopathologic findings showed that some scattered spindle-shaped cells containing melanin pigment in the upper dermis were positive for Fontana-Masson stain and these cells were positive for S-100 protein and MART-1.

A Case of Uncommon Acquired Dermal Melanocytosis / 대한피부과학회지

Dermal melanocytosis includes a variety of congenital and acquired conditions characterized by a sparse population of intradermal dendritic, variably pigmented, spindle-shaped melanocytes. Mongolian spot, Ota's and Ito's nevi are usually present at birth or appear in early childhood. But, several types of acquired dermal melanocytosis that usually appear in adults have been reported. A 47-year-old woman presented with asymptomatic, multiple, symmetric, brownish to black colored macules on the nasal ala, both palms and both feet dorsum that had been there for 10 years. Histopathologic findings showed that some scattered spindle-shaped cells containing melanin pigment in the upper dermis were positive for Fontana-Masson stain and these cells were positive for S-100 protein and MART-1.

Cytomegalovirus Infection in Idiopathic Inflammatory Bowel Disease: Clinicopathologic Analysis of 6 Cases

Cytomegalovirus (CMV) infection is an uncommon association with idiopathic inflammatory bowel disease (IBD) often leading to a variety of serious complications. A total of 41 resected cases of IBD were examined to elucidate the pathologic features of intestinal CMV infection which was assessed by histologic examination and confirmed by immunohistochemistry with CMV antibody. Six cases were positve for CMV antibody; five cases in 19 ulcerative colitis (UC, 26.3%) and one case in 22 Crohn's disease (CD, 4.5%). Of 7 cases of the steroid-treated UC group, five cases were superinfected with CMV (71.4%) but none in 12 cases of the steroid-untreated UC group. All of the five CMV-positive cases in UC showed deep ulceration and transmural inflammation, while none of 10 UC cases without above features were CMV positive. Fibrinoid necrosis and thrombi were found in 83.3% of the CMV infected group, while none in the CMV-negative group of UC cases (p=0.01). We conclude that IBD, particularly UC, is susceptible to the CMV infection when steroid hormone is administered, and that deep colonic ulceration, transmural inflammation and fibrinoid necrosis of vasculature may suggest superinfection of CMV in UC patients. It seems that deep colonic ulceration may be the consequence of an ischemic change following vascular luminal occlusion or vasculitis by CMV infection.