Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. MATERIALS AND METHODS: Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString’s nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. RESULTS: Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. CONCLUSION: In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

Clinical features and treatment outcomes of blastic plasmacytoid dendritic cell neoplasm: a single-center experience in Korea

BACKGROUND/AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that typically presents in the form of skin manifestations with or without lymph node and bone marrow involvement. Given its rarity and recent recognition as a distinct pathological entity, no standard of treatment exists for this aggressive disease and its prognosis is particularly dismal. METHODS: We retrospectively analyzed clinical features and treatment outcomes of patients who were diagnosed with BPDCN between 2000 and 2014. RESULTS: Ten patients had a median age at diagnosis of 41 years (range, 18 to 79), and seven patients were male. Sites of disease involvement were the skin (n = 7), lymph node (n = 5), bone marrow (n = 2), liver (n = 2), spleen (n = 2), and soft tissue (n = 1). Intensified chemotherapy regimens such as hyperCVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine), and VPDL (vincristine, methylprednisolone, daunorubicin, L-asparaginase) were used as a first-line treatment. Although all patients treated with intensified chemotherapy showed an objective response (five patients with complete response) with median progression-free survival of 11.2 months (range 6.2 to 19.4), complete remission was not sustained for more than 2 years in any case. The response was relatively long-lived compared with previously reported CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, but the above regimens do not result in long-term remission. CONCLUSIONS: All patients treated with hyperCVAD or VPDL showed an objective response, but the duration of response was relatively short. Thus, the development of more effective induction as well as consolidation treatment strategy should be warranted to improve this rare disease entity.

Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance. MATERIALS AND METHODS: Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed. RESULTS: Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis. CONCLUSION: PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.

Clinicopathologic Features and Long-Term Outcomes of Elderly Breast Cancer Patients: Experiences at a Single Institution in Korea / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to assess the tumor characteristics and long-term clinical outcomes of adjuvant treatments after surgery with a curative aim for patients with breast cancer who are 65 years and older. MATERIALS AND METHODS: Patients with breast cancer who underwent curative surgery from 2000 to 2009 were analyzed (n=4,388). Tumor characteristics and survival outcome were compared by dividing the patients into two age groups (< 65 and ≥ 65 years old). The Kaplan-Meier method was used for comparison of survival rates by log-rank test, and a Cox regression model was used to examine the effect of variables. RESULTS: Among 4,388 patients with invasive breast cancer, 317 patients (7.2%) were 65 years or older and the median age of all patients was 47 years (range, 18 to 91 years). Tumor characteristics were similar between the two age groups, but the older patients were treated less often with adjuvant treatments. During a median follow-up period of 122 months, recurrence-free survival (RFS) was equivalent for patients 65 years and older compared to younger patients, but significantly worse in overall survival (OS) and breast cancer–specific survival (BCSS) (5-year OS, 94.3% vs. 90.5%; p < 0.001 and 5-year BCSS, 94.7% vs. 91.8%; p=0.031). In the multivariate model, age ≥ 65 years old was identified as an independent risk factor for OS and RFS. CONCLUSION: Elderly breast cancer appeared to have worse outcomes with very low prevalence in Korea, despite similar tumor characteristics. More active adjuvant therapies would have a role for aggressive subtypes for fit, elderly patients.

Idiopathic Phlebosclerotic Colitis: A Rare Entity of Chronic Ischemic Colitis / 대한소화기학회지

Colonic wall thickening is frequently encountered in various conditions, from acute or chronic inflammatory disease to colorectal carcinoma. Colonic wall thickening may be accompanied by calcifications in mucinous adenocarcinoma of the colon, leiomyosarcoma of the colon, schistosomiasis japonica, and phlebosclerotic colitis. Phlebosclerotic colitis is a rare entity of chronic ischemic colitis associated with sclerosis and fibrosis of mesenteric veins. Although its development is usually insidious, and, thus its diagnosis can be delayed, characteristic findings in phlebosclerotic colitis are calcifications of mesenteric veins as well as colonic wall thickening with calcifications. We report on a 71-year-old woman who presented with chronic diarrhea and intermittent hematochezia, who was first misdiagnosed as mucinous adenocarcinoma of the colon, but finally diagnosed as a rare entity of chronic ischemic colitis, phlebosclerotic colitis. Differential points of phlebosclerotic colitis from other diseases, including leiomyosarcoma and schistosomiasis japonica, are also described.

Long-term Successful Treatment of Massive Distal Duodenal Variceal Bleeding with Balloon-occluded Retrograde Transvenous Obliteration / 대한소화기학회지

Duodenal variceal bleeding in patients with portal hypertension due to cirrhosis or other causes is uncommon. We report on a case of a 55-year-old male with an ectopic variceal rupture at the distal fourth part of the duodenum who presented with massive hematochezia and shock. Shortly after achievement of hemodynamic stability, due to the limitation of an endoscopic procedure, we initially attempted to find the bleeding focus by abdominal computed tomography, which showed tortuous duodenal varices that drained into the left gonadal vein. He was treated with first-line balloon-occluded retrograde transvenous obliteration (BRTO), resulting in a favorable long-term outcome without rebleeding three years later. This case suggests that BRTO may be a first-line therapeutic option for control of ruptured duodenal varices, especially at a distal location.

A Case of Isolated Small Intestinal Wall Calcification on Patient with Continuous Ambulatory Peritoneal Dialysis / 대한소화기학회지

The metastatic calcification is defined as the deposition of calcium salt in normal tissue with an abnormal serum biochemical environment, such as chronic kidney disease, hyperparathyroidism, and hypercalcemia related with malignancy. Although the metastatic calcification can develop in any organs and tissues, presenting its symptoms and complications are rare. Thus a few cases have been reported. This case shows the metastatic calcification of the small intestine without any peritoneal and mesenteric vascular calcification which was early diagnosed by computed tomography and mesenteric angiography in a patient with abdominal pain, receiving continuous ambulatory peritoneal dialysis due to end stage renal disease. The clinician should early consider the metastatic calcification as differential diagnosis when unidentified calcifications are noted in simple abdominal X-ray such as in the present case, and promptly confirm it by using appropriate diagnostic tests in order to prevent its complications and progression.

Disseminated Cryptococcosis with Cutaneous Manifestation in a Renal Transplant Recipient: A Case Report / 대한이식학회지

Cryptococcosis commonly affects patients with immune dysfunction, as in the case of immunosuppression in organ transplant patients or as acquired immunodeficiency syndrome in patients afflicted with human immunodeficiency virus. The varied appearance of cryptococcal skin lesion makes clinical diagnosis of cutaneous cryptococcosis difficult. Cryptococcosis proves to be a fatal fungal infection in the immunocompromised patient. Therefore, diagnosis and early treatment of cryptococcosis become vital. A 56-year-old renal transplant recipient, with an ongoing immunosuppression regimen of cyclosporine, prednisolone, and mycophenolate mofetil, was admitted with a 2-week history of pain and edema of right arm without respiratory symptoms. Despite empiric antibiotic therapy, the patient continued to complain of severe tenderness of the involved arm and fever persisted as well. On the third day of hospital stay, a biopsy of the erythematous skin lesion was acquired. On the eighth day of hospital stay, results of both skin biopsy and blood cultures showed the presence of Cryptococcus neoformans. The treatment was begun with intravenous fluconazole (400 mg/day). After 4 days of antifungal treatment, the patient developed fever along with cough with purulent sputum. As the new developing symptoms were suggestive of pneumonia, especially of pulmonary cryptococcosis, the antifungal agent was changed from fluconazole to amphotericin B treatment (0.8 mg/kg, 50 mg/day). Chest computer tomography showed improvement in the pneumonic infiltration and consolidation after 4 weeks of amphotericin B treatment. In conclusion, cellulitis in immunocompromised patients should be suspected in case of highly atypical infectious etiology, and skin biopsy should not be delayed if empiric antibiotic therapy does not control the inflammatory response. Additionally, the patient should be treated with intravenous amphotericin B treatment in case of severe cryptococcosis.

A Case of Vertebral Osteomyelitis With Epidural Abscess Caused by Mycobacterium intracellulare in a Rheumatoid Arthritis Patient

Mycobacterium avium complex (MAC) is the most common pathogen in nontuberculous mycobacterial lung diseases, but vertebral osteomyelitis caused by MAC is rare. We experienced a case of vertebral osteomyelitis with epidural abscess in a rheumatoid arthritis patient who received immunosuppressive agents. Initial assessment was tuberculous vertebral osteomyelitis, and then treated with antituberculous drugs. Fifty-six days later, Mycobacterium intracellulare was identified from abscess culture and drugs were altered to clarithromycin, rifabutin, and ethambutol. After 3 months of M. intracellulare treatment, the radiological findings showed increases of epidural abscess. According to the suseptibility, the patient received intravenous amikacin for four weeks, and then, oral ciprofloxacin in addition to clarithromycin, rifabutin, and ethambutol. The patient is being treated with the medication for 13 months and currently showing slow improvements.

A Case of Transient Ischemic Attack and Cardiomyopathy Presented with Pheochromocytoma / 대한내과학회지

Patients with pheochromocytoma show a variety of clinical symptoms secondary to excessive catecholamine secretion. Major symptoms include hypertension, headache, hyperhidrosis, and palpitation. Stroke and myocardial infarction are known to occur in patients with pheochromocytoma, but the incidence is low. Here, we describe a 45-year-old female with a previous history of transient ischemic attack and a clinical presentation mimicking acute myocardial infarction with transient takotsubo-like myocardial dysfunction. A subsequent diagnostic examination revealed a left adrenal pheochromocytoma. The patient recovered with intensive medical treatment, including alpha- and beta-adrenergic blockade. Follow-up echocardiography revealed normalized cardiac function and wall motion. Thereafter, the patient underwent a laparoscopic left adrenalectomy without complications.

A Case of Congenital Nephrogenic Diabetes Insipidus with Bilateral Hydronephrosis and Hydroureter / 대한신장학회잡지

We describe a case of congenital nephrogenic diabetes insipidus with severe dilatation of bilateral urinary tracts without anatomical obstructions. Functional obstruction can be occurred when polyuria surpasses the transporting ability of urine in the urinary tract. The patient was admitted to our hospital due to decreased mentality developed after traffic accident. On radiologic study, bilateral hydronephrosis and hydroureter were noted. Because the patient excreted copious dilute urine, we performed water deprivation test and the result was consistent with nephrogenic diabetes insipidus. We are presenting this case in an attempt to describe strong association between congenital diabetes insipidus and nonobstructive hydronephrosis in which polyuria is responsible for the hydronephrosis.