Increased Radiosensitivity of Solid Tumors Harboring ATM and BRCA1/2 Mutations / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Preclinical data indicate that response to radiotherapy (RT) depends on DNA damage repair. In this study, we investigated the role of mutations in genes related to DNA damage repair in treatment outcome after RT. @*Materials and Methods@#Patients with solid tumor who participated in next generation sequencing panel screening using biopsied tumor tissue between October 2013 and February 2019 were reviewed and 97 patients that received RT were included in this study. Best response to RT and the cumulative local recurrence rate (LRR) were compared according to absence or presence of missense, nonsense, and frameshift mutations in ATM and/or BRCA1/2. @*Results@#Of the 97 patients, five patients harbored mutation only in ATM, 22 in only BRCA1/2, and six in both ATM and BRCA1/2 (ATMmtBRCAmt). Propensity score matching was performed to select the control group without mutations (ATMwtBRCAwt, n=33). In total, 90 RT-treated target lesions were evaluated in 66 patients. Highest objective response rate of 80% was observed in ATMmtBRCAmt lesions (p=0.007), which was mostly durable. Furthermore, the cumulative 1-year LRR was the lowest in ATMmtBRCAmt lesions and the highest in ATMwtBRCAwt lesions (0% vs. 47.9%, p=0.008). RT-associated toxicities were observed in 10 treatments with no significant difference among the subgroups (p=0.680). @*Conclusion@#Tumors with ATM and BRCA1/2 mutations exhibited superior tumor response and local control after RT compared to tumors without these mutations. The results are hypothesis generating and suggest the need for integrating the tumor mutation profile of DNA repair genes during treatment planning.

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group / Journal of the Korean Cancer Association, 대한암학회지

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations. @*Materials and Methods@#In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1. @*Results@#The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths. @*Conclusion@#Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

The p90rsk-mediated signaling of ethanol-induced cell proliferation in HepG2 cell line

Ribosomal S6 kinase is a family of serine/threonine protein kinases involved in the regulation of cell viability. There are two subfamilies of ribosomal s6 kinase, (p90rsk, p70rsk). Especially, p90rsk is known to be an important downstream kinase of p44/42 MAPK. We investigated the role of p90rsk on ethanol-induced cell proliferation of HepG2 cells. HepG2 cells were treated with 10~50 mM of ethanol with or without ERK and p90rsk inhibitors. Cell viability was measured by MTT assay. The expression of pERK1, NHE1 was measured by Western blots. The phosphorylation of p90rsk was measured by ELISA kits. The expression of Bcl-2 was measured by qRT-PCR. When the cells were treated with 10~30 mM of ethanol for 24 hour, it showed significant increase in cell viability versus control group. Besides, 10~30 mM of ethanol induced increased expression of pERK1, p-p90rsk, NHE1 and Bcl-2. Moreover treatment of p90rsk inhibitor attenuated the ethanol-induced increase in cell viability and NHE1 and Bcl-2 expression. In summary, these results suggest that p90rsk, a downstream kinase of ERK, plays a stimulatory role on ethanol-induced hepatocellular carcinoma progression by activating anti-apoptotic factor Bcl-2 and NHE1 known to regulate cell survival.

Pancoast Syndrome Accompanied by Rotator Cuff Tear

Pancoast syndrome (PS) is characterized by a malignant neoplasm of the superior sulcus of the lung with destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves. The most common initial symptom of PS is shoulder pain; however, cough, dyspnea, and hemoptysis, signs often associated with lung cancer, are not as common. Investigation of PS can be difficult even with plain radiographs of the chest because it is surrounded by osseous structures such as the ribs, vertebral bodies, and manubrium. Due to these characteristics, orthopedic surgeons tend to make a misdiagnosis resulting in delay of appropriate treatment. Here we report on a patient who was supposed to undergo rotator cuff repair for his shoulder pain and weakness, and was eventually diagnosed with PS.

Anti-inflammatory Effects of Flavonoids on TNBS-induced Colitis of Rats

It has been shown that the extracts including eupatilin and quercetin-3-beta-D-glucuronopyranoside had mucoprotective effects on the esophagus and stomach through their antioxidant activities. This study was designed to investigate the anti-inflammatory effect of these flavonoid compounds in an animal model of inflammatory bowel disease induced by 2,4,6-trinitrobenzene sulfonic acid. Experimental colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid. Extracts including eupatilin or quercetin-3-beta-D-glucuronopyranoside were orally administered to animals 48, 24, and 1 h prior to the induction of colitis and then again 24 h later. The animals were sacrificed 48 h after by 2,4,6-trinitrobenzene sulfonic acid treatment and the macroscopic appearance of the colonic lesions was scored in a blinded manner on a scale of 1 to 10. The inflammatory response to colitis induction was assessed by measuring myeloperoxidase activity, nitric oxide production, tumor necrosis factor-alpha expression, total glutathione levels, and malondialdehyde concentrations in the colon. The results indicated that extracts including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside dose-dependently improved the morphology of the lesions induced by 2,4,6-trinitrobenzene sulfonic acid and reduced the ulcer index accordingly. In addition, rats receiving extracts including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside showed significantly decreased levels of mucosal myeloperoxidase activity, nitric oxide production, tumor necrosis factor-alpha expression, and malondialdehyde levels, and increased total glutathione levels. Extracts including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside ameliorated the inflammatory response and colonic injury in acute colitis by decreasing oxidative stress and neutrophil activation. Extracts including eupatilin and extracts including quercetin-3-beta-D-glucuronopyranoside may inhibit acute colitis.

Pancoast Syndrome Accompanied by Rotator Cuff Tear

Pancoast syndrome (PS) is characterized by a malignant neoplasm of the superior sulcus of the lung with destructive lesions of the thoracic inlet and involvement of the brachial plexus and cervical sympathetic nerves. The most common initial symptom of PS is shoulder pain; however, cough, dyspnea, and hemoptysis, signs often associated with lung cancer, are not as common. Investigation of PS can be difficult even with plain radiographs of the chest because it is surrounded by osseous structures such as the ribs, vertebral bodies, and manubrium. Due to these characteristics, orthopedic surgeons tend to make a misdiagnosis resulting in delay of appropriate treatment. Here we report on a patient who was supposed to undergo rotator cuff repair for his shoulder pain and weakness, and was eventually diagnosed with PS.

Failure to Remove a Trochanteric Entry Femoral Nail and Its Cause in Adolescent Patients: Two Cases Report

Trochanteric entry femoral nails have been widely used for fixation of femoral shaft fractures because of easier identification of the entry point. Young patients usually request removal of the nail after healing of the fracture. We experienced a failure and difficulty in removal of the trochanteric entry nail in two adolescent patients. In the patient in which the nail could be removed with difficulty, dense compact bone was formed through the empty interlocking holes and the nail was held just like a latch. This finding was quite similar to the computed tomography findings of the patient in which the nail could not be removed. In order to remove the nail, the newly formed, dense compact bone in the interlocking holes must be broken and detached from the femur itself. We suggest that dense compact bone through the empty interlocking holes might be a clue for difficult removal of the trochanteric entry nail.

Cost Analysis for Dentures Performed at Dental Clinics in Korea / 보건행정학회지

BACKGROUND: The purpose of this study is to analyze the cost for the denture treatment in accordance with the government's plan to expand the National Health Insurance coverage for dental prothesis from July 1, 2012. METHODS: We developed the draft of classification of the treatment activities based on the existing researches and expert's review and finalized the standard procedures through confirming by Korean Dental Association. We also made the list of input at each stage of treatments. We conducted survey of 100 dental clinics via post from April 4 to May 20 in 2011 and 37 clinics took part in the survey. The unit of cost calculation is the process from the first visit for denture treatment to setting of denture and adjustment. The manufacturing process performed by dental technician was not included in the cost analysis. RESULTS: The process for the complete denture treatment was classified with 10 stages. The partial denture treatment was classified with 8 stages. The treatment time per each denture is about 5.6 hours for complete dentures and about 6.6 hours for partial dentures. The treatment cost were from 591,108 won to 643,913 won for complete denture and from 670,219 won to 738,840 won for partial denture in 2011, depending on the location, type of the clinics and the types of physician's income. CONCLUSION: This study shows the example of cost analysis for the treatment to set the fee schedule. Measures to get representative and accurate information need to be made.

Ifosfamide-induced Fanconi syndrome with diabetes insipidus

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m2, a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication.

Arthroscopic Treatment of Cam Type Femoroacetabular Impingement: Short Term Results / 대한고관절학회지

PURPOSE: We evaluated the short term results after treatment of cam type femoroacetabular impingement (FAI) by arthroscopy. MATERIALS AND METHODS: We evaluated the clinical and radiological results of arthroscopically treated cam type FAI in patients who had failed conservative treatment with hip pain, with at least 12 months follow-up, from November 2010 to December 2012. There were 19 males and six females. Mean age of patients was 32.9 years (19-57 years) and mean follow up period was 17.2 months (13-31 months). We analyzed the alpha angle, head neck offset, visual analogue scale (VAS), and modified Harris hip score (MHHS). RESULTS: Mean alpha angle improved from 64.8degrees to 39.9degrees and mean head neck offset also improved from 0.8 to 7.6 mm. Peripheral longitudinal and radial fibrillated labral tear was the most common in the anterosuperior quadrant. Damage to acetabular cartilage was identified in 14 patients. Mean VAS improved from 6.3 to 0.9 and mean MHHS improved from 51.7 to 73.6. Complications associated with the operation included three cases of femoral head articular cartilage injury, two cases of pudendal nerve injury, and two cases of lateral femoral cutaneous nerve injury. CONCLUSION: Although the short term results for arthroscopically treated cam type FAI were satisfactory, care must be taken to reduce the complications associated with arthroscopy and long term follow is needed in order to determine whether or not it can reduce osteoarthritis of the hip.

Factors Associated with Diabetic Retinopathy and Nephropathy Screening in Korea: The Third and Fourth Korea National Health and Nutrition Examination Survey (KNHANES III and IV)

This cross-sectional study was done to identify and determine the socio-demographic and health-related factors associated with diabetic retinopathy and nephropathy screening in Korea. Participants included 2,660 adults, aged 40 or older, with diabetes. Of the 2,660 adults, 998 (37%) and 1,226 (46.1%) had received a diabetic retinopathy and a nephropathy screening within one year, respectively. Regarding retinopathy, subjects older than 65, living in urban areas, with high educational levels, and with self-reported "unhealthy" status were likely to receive annual screening. Subjects living in urban areas, with higher educational levels, with self-reported "fair" or "unhealthy" status, and with 1 to 2 co-morbidities were likely to receive annual nephropathy screening. The Korea Composite Stock Price Index (KOSPI) continued to rise until 2007 when it started to decline over the subsequent years, following the same curve as the diabetic retinopathy and nephropathy screening rates during that time. Together with the financial matter, lack of patient education proved to be a hindrance to diabetes-related screening. The relatively low screening rates in Korea compared to the Western countries are likely to be due to the difference in the health system, economic situations and national demographics.

Comarison of Acridine Orange and Gram Stains in the Diagnosis of Infectious Keratitis

We assessed the comparatice sensitivity and specificity of acridine orange and Gram stains of corneal scrapings from 29 cases of presumed infectious keratitis. The corneal scrapings were placed on two clear glass slides and allowed to air dry. The slides were fixed in 95% methanol for 2 minutes and each slide was stained by Gram and acridine orange stains respectively. Culture was done with another corneal scraping. Cultures were positive in 19 of 29 cases(66%). Among them 14 cases (74%) were positive in Gram stain and 18 cases (95%) were positive in acridine orange stain. So the sensitivity of acridine orange was greater than that of Gram stain. In the specificity, Gram stain (80%) was better than acridine orange stain(50%). This study demonstrates acridine orange stain as well as gram stain is useful as a simple, rapid screening test for the diagnois of suspected infectious keratitis.

Changes of Preoperative and Postoperative Anterior Chamber Depth in Phacoemulsification and Planned Extracapsular Cataract Extraction

To compare the preoperative and postoperative anterior chamber depths in cataract surgery, we performed phacoemulsification followed by posterior chamber intraocular lens(PCIOLs) implantation on 20 eyes(Group I) and planned extracapsular cataract extraction(p-ECCE) followed by PCIOLs implantation on 20 eyes(Group II). After that, we measured prospectively the preoperative anterior chamber (AC) depths and postoperative AC depths 1, 3, 7, 30 and 60 days by using a Scheimpflug camera. The preoperative mean values of AC depths were 2.93mm in Group I and 2.71mm in Group II. In Group I, the postoperative AC depth was increased significantly compared to preoperative AC depth and the difference between preoperative and postoperative AC depth was maintained from the first day of measurement to day 60(p<0.001). In Group II, AC depth of the postoperative day 1 was significantly increased compared to the preoperative depth(p<0.001), but it was slightly decreased at postoperative day 30(p=0.002) and day 60(p=0.02). And there were no significant differences between Group I and Group II in changed of AC depth. The result implies that AC depth was increased significantly after both phacoemulsification and p-ECCE.