In stroke patients, upper extremity deep vein thrombosis (UEDVT) is uncommon compared with lower extremity. Unlike the blood stasis in lower extremity, UEDVT has been developed by secondary cause. We reported a case of stroke patient with repeated UEDVT, presenting superficial venous congestion, who was finally diagnosed with pulmonary adenocarcinoma. The cause of stroke was non-bacterial thromboembolism formed at the mitral valve. Our case shows that unexpected UEDVT should be closely evaluated for higher coagulable status such as a malignancy.

Purpose: This study was conducted to investigate the clinical characteristics of patients with advanced non–small cell lung cancer (NSCLC) harboring human epidermal growth factor receptor 2 (HER2) mutations and to evaluate response to standard treatment and HER2-targeted agents. Materials and Methods: Using tissue and/or blood next-generation sequencing, we identified 44 patients with NSCLC harboring HER2 mutations who were treated at Severance Hospital between December 2016 and February 2021. Clinical data, including patient characteristics, mutation status, incidence of metastasis for distant lesions, and response to chemotherapy, were retrospectively analyzed. Results: The median age was 58 years, and 61% of the patients were female. Most patients (64%) were never-smokers. Adenocarcinoma was the most predominant subtype (98%). A total of 66% of the patients had extrathoracic metastatic lesions, and 32% had intracranial lesions at initial presentation. The median time to the development of brain metastasis was 15.6 months (range, 2.4 to 43.7). The most common type of HER2 mutation was 12 base pair in-frame insertion in exon 20, A775_G776insYVMA. Of the 44 patients, two had concomitant driver mutations, one with epidermal growth factor receptor (EGFR) mutation (V769M), and one with BRAF mutation (V600E). Patients treated with pemetrexed-based chemotherapy (75%) had an overall response rate (ORR) and progression-free survival (PFS) of 30% and 8.3 months (95% confidence interval [CI], 3.9 to 12.7), respectively. The ORR and PFS of HER2-targeted agent treated patients (14%) were 0.0% and 1.9 months (95% CI, 0.1 to 2.8), respectively. Conclusion Given its distinct characteristics and treatment responses, novel treatment strategies for HER2-mutant NSCLC should be developed promptly to improve survival outcomes of patients.

Background: Given the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi. Methods The KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate. Accrual is expected to be completed in 2022, followed by presentation of results in 2023.

In acute stroke, emboli are mostly composed of thrombi from artery, cardiac chamber, valve and vein. Non-thrombotic emboli are sometimes difficult to identify the origin. According to the increased number of cancer patients, now 10% of stroke patients have a cancer. However, the potential mechanisms of stroke in patients with cancer are various. We presented a case of serious acute arterial occlusion with a tumor embolus, which was revealed by histopathologic analysis of retrieved emboli during mechanical thrombectomy.

Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Background/Aims: Frequent bleeding after endoscopic resection (ER) has been reported in patients with end-stage renal disease (ESRD). We aimed to evaluate the association and clinical significance of bleeding with ER in ESRD patients on dialysis. Methods: Between February 2008 and December 2018, 7,571 patients, including 47 ESRD patients on dialysis who underwent ER for gastric neoplasia, were enrolled. A total of 47 ESRDpatients on dialysis were propensity score-matched 1:10 to 470 non-ESRD patients, to adjust for between-group differences in variables such as age, sex, comorbidities, anticoagulation use, tumor characteristics, and ER method. Matching was performed using an optimal matching algorithm. For the matched data, clustered comparisons were performed using the generalized estimating equation method. Medical records were retrospectively reviewed. Frequency and outcomes of post-ER bleeding were evaluated. Results: Bleeding was more frequent in the ESRD with dialysis group than in the non-ESRD group. ESRD with dialysis conferred a significant risk of post-ER bleeding (odds ratio, 6.1; 95% confidence interval, 2.7–13.6; p<0.0001). All post-ER bleeding events were controlled using endoscopic hemostasis except in 1 non-ESRD case that needed surgery. Conclusions ESRD with dialysis confers a bleeding risk after ER. However, all bleeding events could be managed endoscopically without sequelae. Concern about bleeding should not stop endoscopists from performing ER in ESRD patients on dialysis.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic

We have examined isolation and identification protocols for three virus simulant candidates to biological warfare agents. MS2 phage, a simulant for yellow fever virus and Hantaan virus, was propagated using as a host an E. coli strain with F pilus. MS2 phage genome was examined by reverse transcription and polymerase chain reaction (RT-PCR). Coat protein of the phage preparation was examined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometric analysis. Cydia pomonella granulosis virus (CpGV) is a virus simulant candidate to smallpox virus. CpGV was isolated from a commercialized CpGV pellet. In this study, we developed new isolation and identification protocols for CpGV. One disadvantage of using CpGV is that it is not easy to determine viability of the virus. Here, we have included T4 phage as an alternative. We established a high titer production protocol and developed an easy genome identification protocol that does not require purified phage DNA. Stability of these virus preparations was also examined under various storage conditions. When the virus preparations were not subjected to freeze drying, MS2 phage was most stable when it was stored in liquid nitrogen but unstable at 4℃. In contrast, T4 phage was most stable when it was stored at 4℃. CpGV was stable at −20℃ but not at 4℃. Stability during or after freeze drying was also investigated. The result showed that 70~80% MS2 survived the freeze drying process. In contrast, only about 15% of T4 phage survived during the freeze drying. CpGV was found to be degraded during freeze drying.
Bacteriophage T4 ; Bacteriophages ; Biological Warfare Agents ; DNA ; Electrophoresis ; Freeze Drying ; Genome ; Granulovirus ; Hantaan virus ; Levivirus ; Nitrogen ; Polymerase Chain Reaction ; Reverse Transcription ; Variola virus ; Yellow fever virus

PURPOSE: Although the standard treatment for patients with locally advanced rectal cancer managed by preoperative chemoradiotherapy (CRT) is a radical resection, local excisions are used in highly-selective cases. Recently, transanal minimally-invasive surgery (TAMIS) has emerged as a feasible technique for local excision of midrectal lesions. We assess the feasibility of using TAMIS to treat patients with locally advanced rectal cancer who showed good response to CRT. METHODS: From October 2010 to June 2013, 35 consecutive patients with rectal cancer managed by using preoperative CRT underwent TAMIS. After a single-incision laparoscopic surgery port had been introduced into the anal canal, a full-thickness local excision with conventional laparoscopic instruments was performed. We retrospectively reviewed a prospectively collected database of these cases. RESULTS: Of the 35 patients analyzed, 18 showed pathologic complete responses and 17 had residual lesions (2 ypTis, 4 ypT1, 9 ypT2, and 2 ypT3); 34 (97.1%) showed clear deep, lateral margins. The median distance of lesions from the anal verge was 5 cm. All procedures were completed laparoscopically, and the median operating time was 84 minutes. No intraoperative events or morbidities were seen in any of the patients, except one with wound dehiscence, who was treated conservatively. The median postoperative hospital stay and follow-up period were 4 days and 36 months, respectively. During the study period, no patients died, but 5 (14.3%) experienced recurrence, including one recurrence at the TAMIS site. CONCLUSION: TAMIS seems to be a feasible, safe modality for treating patients with locally advanced rectal cancer who show good response to preoperative CRT.
Anal Canal ; Chemoradiotherapy* ; Follow-Up Studies ; Humans ; Laparoscopy ; Length of Stay ; Minimally Invasive Surgical Procedures ; Prospective Studies ; Rectal Neoplasms* ; Recurrence ; Retrospective Studies ; Wounds and Injuries

PURPOSE: The recent discovery and characterization of an oncogenic ROS1 gene rearrangement has raised significant interest because small molecule inhibitors are effective in these tumors. The aim of this study was to determine frequency and clinicopathological features associated with ROS1 rearrangement in patients with cholangiocarcinoma (CCA). MATERIALS AND METHODS: A total of 261 patients who underwent surgery for CCA between October 1997 and August 2013 were identified from an international, multi-institutional database. ROS1 rearrangement was evaluated by break-apart fluorescence in situ hybridization using tissue microarrays of these patients. RESULTS: Of 261 CCA evaluated, three cases (1.1%) showed ROS1 rearrangement by fluorescence in situ hybridization (FISH), all of which were derived from intrahepatic origin. ROS1 protein expression was observed in 38 samples (19.1%). Significantly larger tumor size was observed in ROS1 immunohistochemistry (IHC)–negative patients compared with ROS1 IHC–positive patients. ROS1 FISH–positive patients had a single tumor with a median size of 4 cm and well-to-moderate differentiation. Overall, there was no difference in terms of baseline characteristics, overall survival, and recurrence-free survival between ROS1-positive and -negative patients. CONCLUSION: ROS1 rearrangement was detected in 1.1% of CCA patients. Although rare, conduct of clinical trials using ROS1 inhibitors in these genetically unique patients is warranted.
Cholangiocarcinoma* ; Fluorescence ; Gene Rearrangement ; Humans ; Immunohistochemistry ; In Situ Hybridization ; In Situ Hybridization, Fluorescence ; Incidence*