PURPOSE: Perianal adenocarcinoma arising from a chronic anorectal fistula is a rare condition for which the natural history and optimal management are not well established. For that reason, we conducted a retrospective analysis of 5 consecutive patients with a perianal adenocarcinoma arising from a chronic anorectal fistula managed at our institution from January 2014 to December 2015. METHODS: The patients were identified from a prospectively collected colorectal cancer database that included all patients managed for colorectal cancer at our institution. RESULTS: The median age at diagnosis was 64 years (range, 55–72 years). Magnetic resonance imaging (MRI) was the initial investigation for all patients and showed a hyperintense T2-weighted image. One patient underwent an abdominoperineal resection following neoadjuvant chemoradiotherapy and remained disease free during the 12-month follow-up. Three patients received neoadjuvant therapy with intent for surgery, but did not undergo surgery due to either worsening health or metastatic spread. One patient declined intervention. The median overall survival was 10.5 months (range, 2–19 months). CONCLUSION: A high index of suspicion is required to make a clinical diagnosis of an anal adenocarcinoma arising from a chronic fistula. Histologic diagnosis must be achieved to confirm the diagnosis. Multimodal therapy with neoadjuvant chemoradiotherapy followed by abdominoperineal resection is the treatment of choice.
Adenocarcinoma ; Asian Continental Ancestry Group ; Chemoradiotherapy ; Colorectal Neoplasms ; Diagnosis ; Fistula ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Natural History ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Fistula ; Retrospective Studies

Multiple studies have shown that oral antiviral therapies reduced the incidence of hepatocellular carcinoma (HCC) and improved the survival of patients with chronic hepatitis B when compared with that of untreated patients. In particular, entecavir and tenofovir share the qualities of high efficacy in reducing the HBV DNA levels, and they have excellent tolerability and safety. These drugs modified the natural history of liver fibrosis, improve liver function, decrease the incidence of HCC, decrease the need for liver transplantation, and improve survival. Many studies have suggested that long-term antiviral therapy reduces the risk of HCC and liver cirrhosis in patients with chronic hepatitis. The mechanism of these drugs in reducing the risk of HCC is not clear. This article reviews the mechanisms of carcinogenic HBV by conducting a review of the literature on the efficacy of therapy for reducing the risk of HCC. A few recent articles have suggested that tenofovir offers advantages over entecavir in terms of HCC prevention, but these articles have the inherent limitations of observational data. No other head-to-head randomized trials exist. Further randomized studies would help provide stronger evidence of the association between the type of antiviral agent and the HCC outcomes. Only achieving complete viral eradication from the liver will truly decrease the mortality and incidence of HCC.
Antiviral Agents ; Carcinoma, Hepatocellular ; DNA ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Incidence ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Mortality ; Natural History ; Tenofovir

HBV is the most common etiology of both liver cirrhosis and hepatocellular carcinoma in Korea. Despite much progress made, the currently available antiviral therapies cannot eradicate or eliminate this virus. Hence, the benefits and risks of antiviral therapy should be carefully evaluated on an individual basis and within the context of the clinical situation. The ultimate goals of treatment are to decrease the mortality from liver disease. The benefits of antiviral therapy come from prevention of progression of liver disease. Understanding the natural history of chronic HBV infection is a key step in the decision making process to treat patients with chronic HBV infection. Generally, chronic hepatitis B patients in the immune tolerant phase and immune inactive phase are not recommended to undergo antiviral treatment, except for those patients in special conditions (e.g., immunosuppression or anticancer chemotherapy). Chronic hepatitis B patients in the immune active phase are recommended for antiviral therapy. For patients with liver cirrhosis, treatment should be considered when serum HBV DNA is detectable regardless of the serum level of ALT.
Carcinoma, Hepatocellular ; Decision Making ; DNA ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Immunosuppression ; Korea ; Liver Cirrhosis ; Liver Diseases ; Mortality ; Natural History ; Risk Assessment

OBJECTIVE: Pituitary adenomas (PAs) are often detected as incidental findings. However, the natural history remains unclear. The objective of this study was to evaluate the natural history and growth pattern of untreated PAs.METHODS: Between 2003 and 2014, 59 PAs were managed with clinico-radiological follow up for longer than 12 months without any kind of therapeutic intervention. Tumor volumes were calculated at initial and last follow-up visit, and tumor growth during the observation period was determined. Data were analyzed according to clinical and imaging characteristics.RESULTS: The mean initial and last tumor volume and diameter were 1.83±2.97 mL and 13.77±6.45 mm, 2.85±4.47 mL and 15.75±8.08 mm, respectively. The mean annual tumor growth rate was 0.33±0.68 mL/year during a mean observation period of 46.8±32.1 months. Sixteen (27%) PAs showed tumor growth. The initial tumor size (HR, 1.140; 95% confidence interval, 1.003–1.295; p=0.045) was the independent predictive factor that determined the tumor growth. Six patients (11%) of 56 conservatively managed non-symptomatic PAs underwent resection for aggravating visual symptoms with mean interval of 34.5 months from diagnosis. By Cox regression analysis, PAs of last longest diameter over 21.75 mm were a significant prognostic factor for eventual treatment.CONCLUSION: The initial tumor size of PAs was independently associated with the tumor growth. Six patients (11%) of conservatively managed PAs were likely to be treated eventually. PAs of last follow-up longest diameter over 21.75 mm were a significant prognostic factor for treatment. Further studies with a large series are required to determine treatment strategy.
Diagnosis ; Follow-Up Studies ; Humans ; Incidental Findings ; Natural History ; Pituitary Neoplasms ; Prognosis ; Tumor Burden

OBJECTIVE: To analyze the angiographic features and clinical course, including treatment outcomes and the natural course, of fusiform middle cerebral artery aneurysms (FMCAAs) according to their location, size, and configuration.METHODS: We reviewed the literature on adult cases of FMCAAs published from 1980 to 2018; from 25 papers, 112 FMCAA cases, for which the location, size, and configuration could be identified, were included in this study. Additionally, 33 FMCAA cases in our hospital were included, from which 16 were assigned to the observation group. Thus, a total of 145 adult FMCAA cases were included. We classified the FMCAAs according to their location (l-type 1, beginning from prebifurcation; l-type 2, beginning from bifurcation; l-type 3, beginning from postbifurcation), size (small, <10 mm; large, ≥10 mm; giant, ≥25 mm), and configuration (c-type 1, classic dissecting aneurysm; c-type 2, segmental ectasia; c-type 3, dolichoectatic dissecting aneurysm).RESULTS: The c-type 3 was more commonly diagnosed with ischemic symptoms (31.8%) than hemorrhage (13.6%), while 40.9% were found accidentally. In contrast, c-type 2 was more commonly diagnosed with hemorrhagic symptoms (14.9%) than ischemic symptoms (10.6%), and 72.3% were accidentally discovered. According to location, ischemic symptoms and hemorrhage were the most frequent symptoms in l-type 1 (28.6%) and l-type 3 (34.6%), respectively. Most of l-type 2 FMCAAs were found incidentally (68.4%). Based on the size of FMCAAs, only 11.1% of small aneurysms were found to be hemorrhagic, while 18.9% and 26.0% of large and giant aneurysms were hemorrhagic, respectively. Although four aneurysms of the 16 FMCAAs in the observation group increased in size and one aneurysm decreased in size during the observation period, no rupture was seen in any case and there were no significant predictors of aneurysm enlargement. Of 104 FMCAAs treated, 14 cases (13.5%) were aggravated than before surgery and all the aggravated cases were l-type 1.CONCLUSION: While ischemic symptoms occurred more frequently in l-type 1 and c-type 3, hemorrhagic rather than ischemic symptoms occurred more frequently in l-type 3 and c-type 2. In case of l-type 1 FMCAAs, more caution is required in determining the treatment due to the relatively high complication rate.
Adult ; Aneurysm ; Aneurysm, Dissecting ; Dilatation, Pathologic ; Hemorrhage ; Humans ; Intracranial Aneurysm ; Middle Cerebral Artery ; Natural History ; Rupture

No abstract available.
Aortic Valve Stenosis ; Natural History

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant hereditary disorder caused by germline mutation of the MEN1 gene. It is characterized by tumors of the anterior pituitary gland, parathyroid glands, and endocrine pancreas. Thymic carcinoid tumor is uncommon and associated with a high mortality, but its natural history has not been investigated yet. We report a case of asymptomatic MEN 1 with a thymic carcinoid tumor. A 37-year-old man underwent a routine medical checkup and upper gastrointestinal endoscopy revealed a duodenal neuroendocrine tumor (NET). Further studies showed the coexistence of pancreatic tumor, parathyroid hyperplasia, pituitary adenoma, and thymoma. The patient underwent duodenal endoscopic mucosal resection, distal pancreatectomy, subtotal parathyroidectomy, and thymectomy. The pathological test revealed a duodenal NET, pancreatic NET, parathyroid hyperplasia, and thymic carcinoid tumor. He was treated for MEN 1. We report this asymptomatic case of MEN 1 with a literature review.
Adult ; Carcinoid Tumor ; Endoscopy, Gastrointestinal ; Germ-Line Mutation ; Humans ; Hyperparathyroidism ; Hyperplasia ; Islets of Langerhans ; Mortality ; Multiple Endocrine Neoplasia Type 1 ; Multiple Endocrine Neoplasia ; Natural History ; Neuroendocrine Tumors ; Pancreatectomy ; Parathyroid Glands ; Parathyroidectomy ; Pituitary Gland, Anterior ; Pituitary Neoplasms ; Thymectomy ; Thymoma

This tutorial defines the concepts of disease progression in the context of clinical pharmacology. Disease progression describes the natural history of disease, such as pain, or biomarker of drug response, such as blood pressure. The action of a drug, such as inhibiting an enzyme or activating a receptor, leads to a change in disease status over time. Two main types of drug response can be defined based on the pattern of the time course of disease status. The most common is a symptomatic effect equivalent to a shift up or down of the natural history curve. Less common but quite clinically important is a disease-modifying effect equivalent to a change in the rate of disease progression.
Blood Pressure ; Disease Progression ; Natural History ; Pharmacology, Clinical

Stiff-person syndrome is a rare disorder, and the natural history of the syndrome has not been completely ascertained. The symptoms range from mild to severe and can progress over time: the final result can be significant disability. However, this syndrome is often misdiagnosed due to a lack of understanding of the clinical manifestations. We report the case of a patient who presented with slowly progressing gait disturbance and lower extremity pain and was later diagnosed as suffering from stiff-person syndrome. The patient experienced symptomatic improvement after the administration of benzodiazepines. No recurrence of symptoms has been reported. If the characteristic clinical features and electromyography findings of the syndrome are accurately interpreted, diagnosis of patients with abnormal muscle tension can be effectively done.
Autoantibodies ; Autoimmune Diseases ; Benzodiazepines ; Diagnosis ; Electromyography ; Gait ; Humans ; Leg ; Lower Extremity ; Muscle Tonus ; Natural History ; Recurrence ; Spasm ; Stiff-Person Syndrome

Kawasaki disease (KD) is a systemic vasculitis in infants and young children. However, its natural history has not been fully elucidated because the first case was reported in the late 1960s and patients who have recovered are just now entering middle age. Nevertheless, much evidence has raised concerns regarding the subclinical vascular changes that occur in post-KD patients. KD research has focused on coronary artery aneurysms because they are directly associated with fatality. However, aneurysms have been reported in other extracardiac muscular arteries and their fate seems to resemble that of coronary artery aneurysms. Arterial strokes in KD cases are rarely reported. Asymptomatic ischemic lesions were observed in a prospective study of brain vascular lesions in KD patients with coronary artery aneurysms. The findings of a study of single-photon emission computed tomography suggested that asymptomatic cerebral vasculitis is more common than we believed. Some authors assumed that the need to consider the possibility of brain vascular lesions in severe cases of KD regardless of presence or absence of neurological symptoms. These findings suggest that KD is related with cerebrovascular lesions in children and young adults. Considering the fatal consequences of cerebral vascular involvement in KD patients, increased attention is required. Here we review our understanding of brain vascular involvement in KD.
Aneurysm ; Arteries ; Brain ; Central Nervous System ; Child ; Coronary Vessels ; Humans ; Infant ; Middle Aged ; Mucocutaneous Lymph Node Syndrome ; Natural History ; Prospective Studies ; Stroke ; Systemic Vasculitis ; Tomography, Emission-Computed ; Vasculitis ; Vasculitis, Central Nervous System ; Young Adult