Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP / Journal of the Korean Cancer Association, 대한암학회지

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Survival Rate and Prognostic Factors of 26 Cases of Angiosarcoma and 26 Cases of Kaposi Sarcoma: A Korean Single-Center Experience / 대한피부과학회지

Background@#Angiosarcoma (AS) and Kaposi sarcoma (KS) are rare malignant and borderline malignant vascular tumors that may first present to a dermatologist. There are few Korean studies that particularly focus on their survival due to low incidence. @*Objective@#To investigate the survival and prognostic factors among patients with AS and KS, in addition to their clinical features. @*Methods@#Between 2000∼2021, medical records of 26 AS and 26 KS patients at a single center were analyzed retrospectively. Additionally, we calculated the disease specific survival (DSS) and overall survival (OS) of two diseases. @*Results@#The mean age of patients with AS was 72.9 years and 67.3 years for KS. The most common tumor location was the scalp in patients with AS (80.8%) and the foot (65.4%) in those with KS. In patients with AS, 1-year DSS and OS rates were 36.0% and 34.6%, respectively. Five-year DSS and OS rates were 24.0% and 20.2%, respectively. In patients with KS, the 1-year DSS and OS rates were 96.2% and 84.6%, respectively. The 5-year DSS and OS were 91.6% and 58.0%, respectively. Patients who were older or had larger lesions than average had decreased DSS and OS in AS. Among the patients with KS, immunosuppressed status, including human immunodeficiency virus infection, showed reduced OS. @*Conclusion@#Apart from confirming grave survival of AS and favorable survival of KS, patient’s age and size of lesion affect survival outcomes in patients with AS. Otherwise, immunosuppressed status affects survival outcomes in patients with KS.

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.

Evaluation of a Direct Reverse Transcription Loop-Mediated Isothermal Amplification Method without RNA Extraction (Direct RT-LAMP) for the Detection of Lymph Node Metastasis in Early Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Assessing lymph node metastasis, tumor-derived DNA, or tumor-derived RNA has previously been studied in place of immunohistochemical assay. Because a direct reverse transcription loop-mediated isothermal amplification method (direct RT-LAMP) has been previously developed in order to rapidly identify viruses in place of RNA extraction, our team hypothesized that a direct RT-LAMP assay can be employed as a substitute in order to detect tumor involvement of lymph nodes within breast cancer patients. @*Materials and Methods@#A total amount of 92 lymph nodes removed across 40 patients possessing breast cancer were collected at Kyungpook National University Chilgok Hospital between the months of November 2015 and February 2016. All samples were then evaluated and contrasted via both a direct RT-LAMP assay and routine histopathologic examination. @*Results@#The sensitivity and specificity of the direct RT-LAMP assay were 85.7% and 100%, respectively. The positive predictive value and negative predictive value were 100% and 94.4%, respectively. @*Conclusion@#Direct RT-LAMP assay is capable of facilitating the detection of sentinel lymph node metastasis within breast cancer patients intraoperatively possessing an excellent sensitivity via a cost-effective and time-saving manner.

Comparative Study Between Radioisotope Uptake and Fluorescence Intensity of Indocyanine Green for Sentinel Lymph Node Biopsy in Breast Cancer / 한국유방암학회지

Recently, several breast surgeons have reported a new method for sentinel lymph node biopsy (SLNB) by using indocyanine green (ICG) with infrared camera. This study aimed to determine whether the lymph nodes (LNs) with ICG uptake are true SLNs and to assess the reliability of using only ICG for SLNB. Data were prospectively collected between April and September 2021. All palpable LNs were fat-trimmed and ordered from high to low signal of the gamma detector. The degree of radioisotope uptake and brightness of ICG staining of the axillary LNs detected with a fluorescent camera were compared and associated factors were analyzed. Discordance was defined as sentinel LNs (SLNs) showing a single uptake of radioisotope or fluorescence of ICG only, or when the orders of uptake and intensity degree were different between the 2 materials. A total of 79 SLNBs were performed on 78 patients with breast cancer. The breast cancer was classified as cTis-2N0-1. The discordance rate was 14/79 (17.7%) overall and 45/270 (16.7%) of the total retrieved axillary LNs. The first SLNs showed the lowest discordance rate of 6.3%, whereas the second and third SLNs showed higher discordance rates of 27.6% and 60.0%, respectively. There were no associated clinicopathologic factors that affected the discordance between uptake of radioisotope and fluorescence intensity of ICG. The use of ICG alone for SLNB may be insufficient because of the high discordance rates between radioisotopes and ICG uptake. However, the first SLN could be cautiously regarded as a true SLN.

Comparison of three risk stratification models for non-clear cell renal cell carcinoma patients treated with temsirolimus as first-line therapy

Background/Aims@#For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. @*Methods@#This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. @*Results@#Twenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). @*Conclusions@#All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

Peripheral Neuropathies in Patients with Rhabdomyolysis: Clinical Characteristics and Electrodiagnostic Findings in the Acute/Subacute Stage

BACKGROUND: Rhabdomyolysis is a syndrome caused by injury to skeletal muscle and characterized by myalgia and swelling of the affected muscles. Peripheral nerve injury rarely occurs in patients with rhabdomyolysis. METHODS: We reviewed the medical records of 8 consecutive patients with peripheral neuropathies associated with rhabdomyolysis. We assessed the clinical characteristics and electrodiagnostic findings of eight patients. RESULTS: In seven patients, rhabdomyolysis occurred after prolonged immobilization. In one patient, blunt trauma was a cause of rhabdomyolysis. All patients presented with weakness and paresthesia in lower extremities and electrodiagnostic tests showed peripheral nerve injury suggesting sciatic neuropathy or lumbosacral plexopathy. Although rhabdomyolysis itself recovered completely in all patients, neurologic deficits from neuropathy recovered partially and slowly. CONCLUSIONS: Sciatic nerve or lumbosacral plexus was injured in all eight patients. Among the various causes of rhabdomyolysis, prolonged immobilization is associated with development of peripheral neuropathy.

Tacrolimus-Induced Fever in a Patient Undergoing Kidney Transplantation / 대한내과학회지

Tacrolimus is widely used with other immunosuppressive agents to prevent rejection of a kidney transplant (KT). However, tacrolimus-induced fever is very rarely diagnosed. We report a case of tacrolimus-induced fever after KT. A 53-year-old female was diagnosed with cytomegalovirus (CMV) viremia. She had received a KT 2 months previously. Ganciclovir was started immediately at that time. A fever developed on day 12 of admission. Because of dysuria and a residual urine sensation with pyuria, we started intravenous antibiotics to treat urinary tract infection. Although other infectious reasons were ruled out and CMV viremia and the urinary tract infection improved, the fever spike did not improve. Thus, we suspected drug-induced fever. First, the ganciclovir and antibiotics were discontinued. However, the fever continued. To exclude tacrolimus-induced fever, tacrolimus was discontinued and cyclosporine was used with other immunosuppressive agents. Tacrolimus was discontinued after 1 day and the fever was no longer confirmed.

Tacrolimus-Induced Fever in a Patient Undergoing Kidney Transplantation / 대한내과학회지

Tacrolimus is widely used with other immunosuppressive agents to prevent rejection of a kidney transplant (KT). However, tacrolimus-induced fever is very rarely diagnosed. We report a case of tacrolimus-induced fever after KT. A 53-year-old female was diagnosed with cytomegalovirus (CMV) viremia. She had received a KT 2 months previously. Ganciclovir was started immediately at that time. A fever developed on day 12 of admission. Because of dysuria and a residual urine sensation with pyuria, we started intravenous antibiotics to treat urinary tract infection. Although other infectious reasons were ruled out and CMV viremia and the urinary tract infection improved, the fever spike did not improve. Thus, we suspected drug-induced fever. First, the ganciclovir and antibiotics were discontinued. However, the fever continued. To exclude tacrolimus-induced fever, tacrolimus was discontinued and cyclosporine was used with other immunosuppressive agents. Tacrolimus was discontinued after 1 day and the fever was no longer confirmed.

No benefit of hypomethylating agents compared to supportive care for higher risk myelodysplastic syndrome

BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.

Impact of Chronic Kidney Disease in Patients Undergoing Percutaneous Coronary Intervention: Improved but Not Solved

No abstract available.

Acute Kidney Injury due to Rbadomyolysis Complicated with Zolpidem Overdose / 대한내과학회지

Zolpidem (Stilnox®, Handok, Seoul, Korea) is a hypnotic imidazopyridine that is often used to treat insomnia because it has less abuse and addiction potential than benzodiazepines. Its side effects include headache, dizziness, and nausea, but these are mild. Zolpidem intoxication rarely has severe complications. Here, we report a case of acute kidney injury due to rhabdomyolysis related to zolpidem. A 51-year-old man was admitted with drowsy mentality after taking an overdose of zolpidem in a suicide attempt. Laboratory findings showed a blood urea nitrogen of 59.9 mg/dL, serum creatinine of 5.8 mg/dL, and creatine phosphokinase of 16,210 IU/L. Acute kidney injury associated with rhabdomyolysis complicating zolpidem intoxication was diagnosed. The patient was managed with hemodialysis and recovered completely in terms of renal function and muscle enzyme levels.

Milk-alkali syndrome secondary to the intake of calcium supplements / 영남의대학술지

Milk-alkali syndrome (MAS), a triad of hypercalcemia, metabolic alkalosis, and renal failure, is associated with ingestion of large amounts of calcium and absorbable alkali. MAS is the third most common cause of hypercalcemia in hospital, after primary hyperparathyroidism and malignant neoplasm. MAS is not often reported in the Korean literature. We describe MAS secondary to intake of calcium citrate for the treatment of osteoporosis with thoracic spine compression fracture. A 70-year-old man presented to our hospital with a 1-week history of general weakness and lethargy. He was found with acute kidney injury (serum creatinine, 4.6 mg/dL), hypercalcemia (total calcium, 14.8 mg/dL), and alkalosis. Laboratory evaluation excluded both hyperparathyroidism and malignancy. Mental status and serum calcium level was normalized within a week after proper hydration and intravenous administration of furosemide. However, he developed aspiration pneumonia, pseudomembranous colitis, and sepsis with multi-organ failure. Despite intensive treatment including inotropics, mechanical ventilation, and renal replacement therapy, he expired with no signs of renal recovery on the 28th hospital day.

A Case of Salmonella Infection Complicated by Rhabdomyolysis and Acute Kidney Injury / 계명의대학술지

Rhabdomyolysis a clinical syndrome characterized by injury to skeletal muscle and release of intracellular contents into the systemic circulation, can develop from infections, although trauma is a more common cause. Myoglobinuric acute kidney injury (AKI) is a potentially life-threatening complication of rhabdomyolysis. Reports of rhabdomyolysis and AKI induced by salmonella infection are rare in the Korean literature. This paper describes a case of salmonella enteritis complicated by rhabdomyolysis and AKI. A 58-year-old man presented to the hospital with a two day history of watery diarrhea, abdominal pain and high fever. Initial blood chemistry revealed a serum creatinine (Cr) level of 3.4 mg/dL, with elevations of serum creatine phosphokinase (CK, 5,635 IU/L) and serum myoglobin (>3,000 ng/mL). Intravenous hydration and empirical antibiotic treatment with ciprofloxacin were initiated. Blood and stool cultures grew salmonella group B, which was sensitive to ciprofloxacin, ampicillin, and ceftazidime. Parenteral ciprofloxacin was continued for 14 days. During the first week of hospitalization, peak levels of serum Cr and CK were 9.5 mg/dL and 89,155 IU/L, respectively. Thereafter clinical and biochemical parameters gradually improved without dialysis. The patient was discharged on the 20th hospital day with normal CK levels except for serum Cr. His renal function normalized (serum Cr 1.0 mg/dL) two months after discharge. Based on the results of this case, prompt fluid therapy and early administration of antibiotics should be performed in patients with salmonella infection complicated by rhabdomyolysis and AKI.

A Case of Advanced Gastric Cancer Presenting as Multiple Colonic Lymphoid Hyperplasia / 대한소화기학회지

Gastric cancer frequently disseminates to the liver, lung, and bone via hematogeneous, lymphatic, or peritoneal routes. However, gastric adenocarcinoma that metastasize to the colon and that shows typical linea platisca pattern on colonofiberscopy has rarely been reported. Recently, the authors experience a case of advanced gastric cancer with colonic metastases in a 55-year-old female patient. Multiple colonic lymphoid hyperplasias were detected on colonofiberscopy and biopsy revealed metastatic gastric cancer to the colonic wall. She was treated with mFOLFOX (5-FU, oxaliplatin, leucovorin) and has achieved stable disease status without disease progression. Herein, we report a rare case of signet ring-cell gastric cancer which metastasized to the colon in the form of multiple colonic lymphoid hyperplasias.

A Case of Rhabdomyolysis Presenting with Acute Kidney Injury Complicating Carbon Monoxide Poisoning / 대한내과학회지

Carbon monoxide (CO) poisoning has increased rapidly in South Korea and may cause a variety of clinical effects. The most common complications are neurologic and neuropsychological disturbances. However, in rare cases, CO poisoning may also be associated with acute kidney injury and non-traumatic rhabdomyolysis. Here, we report a case of acute kidney injury and rhabdomyolysis complicating CO poisoning. A 32-year-old woman was admitted to our emergency department with dyspnea and confused consciousness after exposure to CO during a suicide attempt involving charcoal briquettes. Laboratory findings revealed a carboxyhemoglobin (COHb) level of 44.8%, a blood urea nitrogen level of 20.5 mg/dL, a serum creatinine level of 1.4 mg/dL, and a creatine phosphokinase level of 8,688.3 IU/L. Acute kidney injury and rhabdomyolysis complicating CO poisoning were diagnosed. This case was managed with normobaric oxygen therapy and hydration. The patient recovered completely with respect to renal function and muscle enzyme level, and COHb level returned to 0%.

Hyperglycemic Hyperosmolar Syndrome Caused by Corticosteroid Therapy in a Patient with IgA Nephropathy / 계명의대학술지

Glucocorticoids are the most common cause of drug-induced diabetes mellitus or hyperglycemia. Hyperglycemic hyperosmolar syndrome (HHS) secondary to glucocorticoid treatment in patients with glomerular disease has rarely been reported in Korea. This paper describes a case of HHS after corticosteroid administration for the treatment of immunoglobulin A (IgA) nephropathy. A 56-year-old nondiabetic male with biopsy-proven IgA nephropathy was started on a combination therapy of an angiotensin converting enzyme inhibitor and oral prednisolone (60 mg, 0.8 mg/kg/day). Eight weeks after the initiation of steroid therapy, he was admitted with a one-week history of polydipsia, polyuria and general weakness. His laboratory tests revealed a serum creatinine level of 2.7 mg/dL, elevated blood glucose (1,221 mg/dL) and an increase in serum osmolarity (347 mOsm/kg H2O). Urinalysis showed 4+ sugars, 2+ proteins, and negative ketones. Prednisolone was tapered and he was administered with intravenous fluids, insulin and electrolytes. The patient was discharged with normoglycemia without the use of antidiabetic medications on the 18th hospital day. Patients who are taking corticosteroids for the treatment of primary glomerulopathy should be investigated for HHS promptly if they present with dehydration, general weakness and weight loss.

Amlodipine intoxication complicated by acute kidney injury and rhabdomyolysis / 영남의대학술지

Amlodipine, a calcium channel blocker of the dihydropyridine group, is commonly used in management of hypertension, angina, and myocardial infarction. Amlodipine overdose, characterized by severe hypotension, arrythmias, and pulmonary edema, has seldom been reported in Korean literature. We report on a fatal case of amlodipine intoxication with complications including rhabdomyolysis and oliguric acute kidney injury. A 70-year-old woman with a medical history of hypertension was presented at the author's hospital 6 hours after ingestion of 50 amlodipine (norvasc) tablets (total dosage 250 mg) in an attempted suicide. Her laboratory tests showed a serum creatinine level of 2.5 mg/dL, with elevated serum creatine phosphokinase and myoglobin. The patient was initially treated with fluids, alkali, calcium gluconate, glucagon, and vasopressors without a hemodynamic effect. High-dose insulin therapy was also started with a bolus injection of regular insulin (RI), followed by continuous infusion of RI and 50% dextrose with water. Despite intensive treatment including insulin therapy, inotropics, mechanical ventilation, and continuous venovenous hemodiafiltration, the patient died of refractory shock and cardiac arrest with no signs of renal recovery 116 hours after her hospital admission.

Erratum: A Case of Acute Kidney Injury in a Patient with Pulmonary Tuberculosis Receiving Ethambutol Therapy / 대한내과학회지

We correct the revised date of this article.