Voriconazole-induced Severe Hyperkalemia Precipitated by Multiple Drug Interactions

Voriconazole, a triazole antifungal agent used to treat serious fungal infections, has a pharmacokinetic characteristic of undergoing hepatic metabolism by the cytochrome P450 system. Few cases of hyperkalemia have been reported, which presented only when the serum voriconazole level was exceptionally elevated by drugdrug interactions. Additionally, azole antifungals may interfere with the biosynthesis of adrenal steroids and therefore can predispose patients to aldosterone deficiency. However, it is unclear whether voriconazole itself can induce hypoaldosteronism or hyperkalemia. Here, we report a case of voriconazole-induced hyperkalemia in a patient administered concurrent medications to treat comorbidities. Voriconazole was orally administered for pulmonary aspergillosis, and three episodes of severe hyperkalemia recurred, which improved with emergency treatment. In the first episode, renin-angiotensin-aldosterone system inhibitors were associated. We found that dronedarone might have increased the voriconazole level in the second episode. At that time, severe hypercalcemia was concurrent, which improved with acute hemodialysis and eliminating dronedarone. Finally, severe hyperkalemia recurred without concurrent medications known to interact with voriconazole. Upon switching from voriconazole to itraconazole, the hyperkalemia was resolved. Drug level monitoring is necessary when voriconazole is used. Genetic susceptibility, such as through CYP2C19 polymorphism, may be investigated for patients with adverse reactions to voriconazole.

Voriconazole-induced Severe Hyperkalemia Precipitated by Multiple Drug Interactions

Voriconazole, a triazole antifungal agent used to treat serious fungal infections, has a pharmacokinetic characteristic of undergoing hepatic metabolism by the cytochrome P450 system. Few cases of hyperkalemia have been reported, which presented only when the serum voriconazole level was exceptionally elevated by drugdrug interactions. Additionally, azole antifungals may interfere with the biosynthesis of adrenal steroids and therefore can predispose patients to aldosterone deficiency. However, it is unclear whether voriconazole itself can induce hypoaldosteronism or hyperkalemia. Here, we report a case of voriconazole-induced hyperkalemia in a patient administered concurrent medications to treat comorbidities. Voriconazole was orally administered for pulmonary aspergillosis, and three episodes of severe hyperkalemia recurred, which improved with emergency treatment. In the first episode, renin-angiotensin-aldosterone system inhibitors were associated. We found that dronedarone might have increased the voriconazole level in the second episode. At that time, severe hypercalcemia was concurrent, which improved with acute hemodialysis and eliminating dronedarone. Finally, severe hyperkalemia recurred without concurrent medications known to interact with voriconazole. Upon switching from voriconazole to itraconazole, the hyperkalemia was resolved. Drug level monitoring is necessary when voriconazole is used. Genetic susceptibility, such as through CYP2C19 polymorphism, may be investigated for patients with adverse reactions to voriconazole.

Adult Idiopathic Renal Fanconi Syndrome: A Case Report

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, 53 mL/min/1.73 m²). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.

The Role of Steroid Sulfatase as a Prognostic Factor in Patients with Endometrial Cancer

PURPOSE: The aim of the study was to determine steroid sulfatase (STS) expression in endometrial cancer patients and its correlation with disease prognosis. MATERIALS AND METHODS: We conducted a retrospective study in 59 patients who underwent surgery with histologically confirmed endometrial cancer from January 2000 to December 2011 at Hanyang University Hospital. Immuno-histochemical staining of STS was performed using rabbit polyclonal anti-STS antibody. RESULTS: Sixteen of the 59 patients (27.1%) were positive for STS expression. Disease free survival (DFS) was 129.83±8.67 [95% confidence interval (CI): 112.84-146.82] months in the STS positive group (group A) and 111.06±7.17 (95% CI: 97.01-125.10) months in the STS negative group (group B) (p=0.92). Overall survival (OS) was 129.01±9.38 (95% CI: 110.63-147.38) months and 111.16±7.10 (95% CI: 97.24-125.07) months for the groups A and B, respectively (p=0.45). Univariate analysis revealed that FIGO stage and adjuvant therapy are significantly associated with DFS and OS. However, in multivariate analysis, FIGO stage and adjuvant therapy did not show any statistical significance with DFS and OS. STS was also not significantly associated with DFS and OS in univariate and multivariate analysis. CONCLUSION: STS expression was not significantly associated with DFS and OS, despite positive STS expression in 27% of endometrial cancer patients. Therefore, the role of STS as a prognostic factor in patients with endometrial cancer remains unclear and requires further research.

A Case of Acute Recurrent Pancreatitis Caused by Branch Duct Type IPMN and Ampulla of Vater Adenoma with High Grade Dysplasia / 대한내과학회지

Acute pancreatitis is an inflammatory disease that can extend to extra-pancreatic tissues and distant organs. Detecting the underlying cause is important because it helps provide an appropriate treatment plan and improve prognosis. An underlying cause cannot be identified after initial evaluation in 10-30% of patients with acute pancreatitis, and they are diagnosed with idiopathic acute pancreatitis. Here, we report a case of a 77-year-old woman with acute recurrent pancreatitis caused by a branch duct-type intraductal papillary mucinous neoplasm (IPMN) and an ampulla of Vater adenoma. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed only IPMN. However, endoscopic retrograde cholangiopancreatography revealed a mucosal abnormality of the ampulla of Vater. The mucosal abnormality was documented to be an ampulla of Vater adenoma with high-grade dysplasia.

A Case of Acute Recurrent Pancreatitis Caused by Branch Duct Type IPMN and Ampulla of Vater Adenoma with High Grade Dysplasia / 대한내과학회지

Acute pancreatitis is an inflammatory disease that can extend to extra-pancreatic tissues and distant organs. Detecting the underlying cause is important because it helps provide an appropriate treatment plan and improve prognosis. An underlying cause cannot be identified after initial evaluation in 10-30% of patients with acute pancreatitis, and they are diagnosed with idiopathic acute pancreatitis. Here, we report a case of a 77-year-old woman with acute recurrent pancreatitis caused by a branch duct-type intraductal papillary mucinous neoplasm (IPMN) and an ampulla of Vater adenoma. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed only IPMN. However, endoscopic retrograde cholangiopancreatography revealed a mucosal abnormality of the ampulla of Vater. The mucosal abnormality was documented to be an ampulla of Vater adenoma with high-grade dysplasia.

A Case of Oncocytic Glomus Tumor of the Larynx / 대한이비인후과학회지

A glomus tumor is a benign neoplasm arising in the soft tissue. The most common affected site for glomus tumor is the subungal area of the finger. Occasionally, it is found in unusual locations, such as stomach, nasal cavity, trachea, mediastinum and bone etc. Oncocytic glomus tumor of the larynx is extremely rare. Laryngeal glomus tumor usually does not express any symptoms at first, but it causes hoarseness or foreign body sensation subsequently when the size of tumor is increased. The main treatment of laryngeal glomus tumor is by complete surgical excision. Recently, we had treated a 41-year-old woman who had an oncocytic glomus tumor of the larynx by CO2 laser excision under suspension laryngoscope. Here, we report the case with a review of literature.

Collision of Three Histologically Distinct Endometrial Cancers of the Uterus

A collision tumor is defined by the presence of two separate masses in one organ, which are pathologically distinct. We described a 70-yr-old patient who complained of abnormal vaginal bleeding with a collision tumor of the uterine corpus. The patient received total hysterectomy, bilateral salphingo-oophorectomy, bilateral pelvic-paraaortic lymphadenectomy, omentectomy, and intraperitoneal chemotherapy. The uterine corpus revealed three separate masses, which were located at the fundus, anterior and posterior wall. Each tumor revealed three pathologically different components, which were malignant mixed mullerian tumor, papillary serous carcinoma, and endometrioid adenocarcinoma. Among these components, only the papillary serous carcinoma component invaded the underlying myometrium and metastasized to the regional lymph node. Adjuvant chemotherapy and radiation therapy were performed. The patient is still alive and has been healthy for the last 8 yr. We have reviewed previously reported cases of collision tumors which have occurred in the uterine corpus.

Castleman's Disease of the Renal Sinus Presenting as a Urothelial Malignancy: A Brief Case Report

Castleman's disease is a rare benign lymphoproliferative disorder that frequently affects lymph nodes of the mediastinal thorax and the neck. It very rarely affects the renal sinus. We report a case of Castleman's disease arising in the renal sinus in a 64-year-old man. The patient visited the hospital with the chief complaint of hematuria. Abdominal computed tomography revealed a homogeneous mass in the sinus of the left kidney, radiologically interpreted as a malignant urothelial tumor. Subsequently, nephroureterectomy was performed, after which microscopic examination of the specimen revealed a diffuse lymphoproliferative lesion with reactive lymphoid follicles of various sizes and prominent plasma cell infiltration of interfollicular spaces, highlighted by immunohistochemical staining for CD138. The lesion was diagnosed as Castleman's disease of the plasma cell type. Although preoperative diagnosis of Castleman's disease is difficult and the incidence is exceedingly rare, it should be considered in the differential diagnosis of renal sinus tumors.

A Case of Elderly-Onset Crescentic Henoch-Schonlein Purpura Nephritis with Hypocomplementemia and Positive MPO-ANCA

Henoch-Schonlein purpura (HSP) is common in childhood and often self-limiting. There have been limited studies on elderly-onset HSP nephritis (HSPN). A 76-yr-old man was transferred to our hospital with a 1-month history of oliguria, abdominal pain, edema and palpable purpura in the legs. Three months ago, he was admitted to another hospital with jaundice, and consequently diagnosed with early common bile duct cancer. The patient underwent a Whipple's operation. Antibiotics were administrated because of leakage in the suture from the surgery. However, he showed progressive renal failure with edema and purpura in the legs. Laboratory investigations showed serum creatinine 6.4 mg/dL, 24-hr urine protein 8,141 mg/day, myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) 1:40 and C3 below 64.89 mg/dL. Renal biopsy showed crescentic glomerulonephritis, as well as mesangial and extracapillary Ig A deposition. We started steroid therapy and hemodialysis, but he progressed to end-stage renal failure and he has been under maintenance hemodialysis. We describe elderly onset HSPN with MPO-ANCA can be crescentic glomerulonephritis rapidly progressed to end stage renal failure.

The Glycolytic Phenotype is Correlated with Aggressiveness and Poor Prognosis in Invasive Ductal Carcinomas / 한국유방암학회지

PURPOSE: Glucose uptake and glycolytic metabolism are enhanced in cancer cells, and increased expression of glucose transporter 1 (GLUT1) has also been reported. The aim of this study was to investigate GLUT1 expression in human breast tissues and invasive ductal carcinomas. METHODS: We used tissue microarrays consisting of normal breast tissue, ductal hyperplasia, ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastases. We examined GLUT1 expression in the microarrays by immunohistochemistry, reviewed the medical records and performed a clinicopathological analysis. RESULTS: Membranous GLUT1 expression was observed in normal and tumor cells. GLUT1 expression was higher in ductal carcinoma in situ, invasive ductal carcinoma, and lymph node metastasis than in normal tissue and ductal hyperplasia (p=0.002). Of 276 invasive ductal carcinomas, 106 (38.4%) showed GLUT1 expression. GLUT1 expression was correlated with higher histologic grade (p<0.001), larger tumor size (p=0.025), absence of estrogen receptor (p<0.001), absence of progesterone receptor (p<0.001), and triple-negative phenotype (p<0.001). In univariate survival analysis, patients with GLUT1 expression had poorer overall survival and disease-free survival (p=0.017 and p=0.021, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, GLUT1 expression was an independent prognostic factor of poorer overall survival and disease-free survival (p=0.017 and p=0.019, respectively). CONCLUSION: GLUT1 expression seems to play an important role in malignant transformation, and the glycolytic phenotype in invasive ductal carcinoma may indicate aggressive biological behavior and a worse prognosis.

Parotid Gland Carcinosarcoma with Osteosarcoma as a Sarcomatous Component: A Case Report with Fine Needle Aspiration Cytologic Findings

Carcinosarcoma of the salivary glands is a rare malignant tumor showing both malignant epithelial and mesenchymal components. Herein, we present a carcinosarcoma of the parotid gland in a 67-year-old man consisting of osteosarcoma and adenocarcinoma components with fine needle aspiration cytological findings. The tumor was composed predominantly of osteosarcoma and small areas of adenocarcinomatous components and a hyalinized nodule reminiscent of pleomorphic adenoma. The tumor showed infiltrative growth features with perineural, lymphatic, and vascular invasion. Despite postoperative adjuvant radiation therapy, multiple metastatic lesions occurred in the both lungs 5 months after surgery. As salivary gland carcinosarcoma has been known to demonstrate highly aggressive behavior, an accurate pathological diagnosis is prerequisite for appropriate treatment.

Discrimination Between Childhood Subacute Necrotizing Lymphadenitis and Nonspecific Cervical Lymph Hyperplasia for Earlier Diagnosis / 소아알레르기및호흡기학회지

PURPOSE: We conducted this research to make an earlier diagnosis and identify better treatment for Kikuchi-Fujimoto disease (KFD) by comparing clinical findings with nonspecifically enlarged cervical lymph nodes in children. METHODS: Nineteen patients were diagnosed with KFD by tissue pathology from a fine needle aspiration biopsy and/or excisional biopsy and were compared with the clinical, radiological, and pathological findings of reactive hyperplasia. RESULTS: The average onset age of onset for patients with KFD was 11.8+/-3.61 years, and the male to female ratio was 1:1.1, whereas patients with reactive hyperplasia were 11.8+/-5.96 years, and the male to female ratio was 1.7:1. Patients with KFD suffered more from fever than patients with reactive hyperplasia (68% vs. 13%, P=0.002). Patients with KFD showed perinodal infiltration (P=0.001) and necrosis on computed tomography, whereas patients with reactive hyperplasia did not show any of these findings. Ultrasonographic findings were similar between the two study groups. In contrast, the histopathological examinations of biopsied cervical lymph nodes were enormously helpful for distinguishing the findings of KFD from those of patients with reactive hyperplasia. CONCLUSION: We recommend a histopathological examination to distinguish KFD from reactive hyperplasia in children with significantly enlarged cervical lymph nodes.

Actinomycosis of the Appendix: A Case Report

Actinomycosis is an uncommon disease caused by actinomycoses, which is a normal flora in the human mucosal membrane. It is difficult to diagnose pre- and intra-operatively and requires long-term use of antibiotics even after surgery. Especially, abdominal actinomycosis is frequently misdiagnosed as a tumor, diverticulitis, chronic inflammatory disease, or other infectious disease preoperatively. Thus, we report the case of a 21-yr-old male patient who was thought to have acute appendicitis and who underwent a cecal wedge resection, including the appendix, with the assistance of laparoscopy for appendiceal actinomycosis.

Cystic Lymphangioma of the Breast in an Adult Woman

Cystic lymphangioma is also known as cystic hygroma, and this is a congenital malformation of the lymphatic system. Most lymphangiomas are present at birth and they are diagnosed by the age of 2. They are mostly located in the neck or axillary region. The breast as a site of origin is an extremely unusual location, and especially in adults. We report here on a case of cystic lymphangioma in a 36-year-old woman. Physical examination revealed a tender cystic mass in the upper outer quadrant of the right breast. Ultrasonography revealed an irregular hypoechoic mass lesion that was associated with irregular duct dilatation and several enlarged axillary lymph nodes. After the operation, the mass was revealed to be a cystic lymphangioma. Although it is very rare, cystic lymphangioma should be considered in the differential diagnosis of a breast mass in adults.

Leptin expression in adenocarcinomas and adenomatous polyps in patients with colon cancer / 대한내과학회지

BACKGROUND: Though leptin, the adipocytes-derived hormone, plays an important role in obesity, it can act as a growth factor for several cancers including gastrointestinal malignancies. Based on this background, we investigated whether leptin expression correlated with the clinicopathological characteristics or disease outcome in patients with colon cancer. We immunohistochemically analyzed the expression of leptin in a "colon adenoma-carcinoma sequence" in the normal colon mucosa, an adenomatous polyp and adenocarcinoma tissue, from a surgical resection for each patient. METHODS: We collected samples from 24 patients with a colorectal adenocarcinoma that was removed in either a total colectomy or hemicolectomy, and who presented with an adenomoatous polyp and an adenocarcinoma in the same surgical specimen. Leptin expression was assessed using immunohistochemical methods and was evaluated by grading the staining intensity as 0, +1, +2, +3. RESULTS: Whereas leptin expression was observed in 4.2% (1/24) of the normal colon mucosa, adenomatous polyps and adenocarcinomas showed 33.3% (8/24) and 50.0% (12/24) expression of leptin, respectively (p<0.05), suggesting that leptin expression in the adenomatous polyps and adenocarcinomas was higher than in the normal colon mucosa (p<0.05). There was no significant difference in leptin expression between the adenomatous polyps and adenocarcinomas, statistically. There was no relationship between leptin expression and patients age, sex, BMI (body mass index), cancer stage, and lymph node metastasis. However, the tumor size in the positive leptin expression group was larger than in the negative leptin expression group (5.6+/-2.2 cm vs 3.9+/-1.4 cm; p<0.05) CONCLUSIONS: Since leptin expression in adenomatous polyps and adenocarcinomas was higher than in the normal colon mucosa and leptin expression significantly correlated with the tumor size, leptin might play a role in the development of an adenomatous polyp and an adenocarcinoma in the colon. However, leptin does not contribute to the progression of colon adenoma, and further evaluation studies will be required.

Primary Synovial Sarcoma of the Thyroid Gland

Synovial sarcoma is a rare but distinct soft tissue neoplasm, most commonly occurring in para-articular regions of the extremities of young adults and also occurring in the head and neck region. To the best of our knowledge, only one case of primary synovial sarcoma of the thyroid has been previously reported. Here, we report a 15-yr-old man who had a chief complaint of a palpable neck mass. The neck computed tomography revealed a relatively well-demarcated solid mass in the left thyroid gland. After fine needle aspiration cytology, total thyroidectomy and lymph node dissection were performed. Grossly, the mass was covered by the same capsule as the thyroid gland, measuring 6X5X5 cm in dimensions and weighing 78 gm. The cut surface showed a well demarcated, lobulated, grayish tan, and rubbery solid tumor. Histologically, this tumor was a biphasic synovial sarcoma. Immunohistochemical, ultrastructural, genetic studies, and cytologic findings were all consistent with synovial sarcoma. When synovial sarcomas arise in this unusual site, recognition and differential diagnosis become more difficult. The differential diagnosis of a spindle epithelial tumor with thymus-like differentiation is very difficult due to their similar clinical, histological, and immunohistochemical features. Ultrastructural and cytogenetic studies for synovial sarcoma are necessary to establish a definitive diagnosis.

The Intestinal Type of Florid Cystitis Glandularis Mimics Bladder Tumor: A Case Report

Cystitis glandularis is a benign metaplastic proliferative lesion of the urinary bladder which usually occurs in the setting of chronic irritation and infection or in some cases as a congenital process. Sometimes it presents as a tumor mass-like florid lesion, grossly mimicking malignancy. We report a case of 59-year-old man with multiple mass lesions around the trigone and the neck portion, which suggested the possibility of malignancy in clinical and radiological evaluations. Final diagnosis was confirmed by transurethral resection. The surface urothelial lining was intact. The submucosa showed von Brunn's nests, cystitis glandularis and cystitis cystica in the edematous lamina propria. There were numerous glands lined by tall columnar, mucin producing epithelium without atypia, conforming to the appearance of the intestinal variant of cystitis glandularis. The cystitis glandularis may mimic a neoplasm on gross evaluation. The intestinal variant of cystitis glandularis is particularly likely to be problematic when florid.

Kikuchi's Disease of the Mesenteric Lymph Nodes Presenting as Acute Appendicitis

Kikuchi's disease is a benign self-limiting necrotizing lymphadenitis that occurs most commonly in young women, and is usually found in the cervical lymph nodes. When there is an unusual location of involved lymph nodes, the diagnosis can be difficult. We recently treated a patient with Kikuchi's disease who had ileocecal mesenteric lymph node involvement; the patient presented with symptoms of acute appendicitis in an 11-year old boy. Although mesenteric lymph node involvement of Kikuchi's disease is very rare, Kikuchi's disease should be added to the differential diagnosis of acute appendicitis in patients with enlarged ileocecal mesenteric lymph nodes on radiological evaluation.

Prognostic Significance of E2F3 Expression in Bladder Cancer / 대한비뇨기과학회지

PURPOSE: E2F3 is important for cell cycle regulation and DNA replication. Recent studies have reported that members of the E2F family can play specific and diverse roles in the tumorigenesis of human malignancies, and the E2F3 expression appears to provide a growth advantage to tumor cells by activating cell proliferation in bladder tumors. We studied the prognostic significance of E2F3 expression in bladder cancer. MATERIALS AND METHODS: We examined the expression of E2F3 with using immunohistochemical staining in the tumor samples from 109 patients suffering with bladder cancer, and we analyzed the prognostic significance of E2F3 according to the grade, stage, recurrence and progression of bladder cancer. RESULTS: We found positive staining for E2F3 in 23 cases (21.1%). The E2F3 expression was correlated with the tumor stage (superficial vs. invasive, p<0.001) and the tumor grade (p=0.001). The E2F3 expression was not correlated with the recurrence and progression of superficial bladder cancer. CONCLUSIONS: In this study, our results showed that the E2F3 expression was observed in a portion of the bladder cancer specimens. These results suggest that E2F3 may contribute to the development of bladder cancer, but it may not play a role as a prognostic factor of bladder cancer.