Urine D-arabinitol/L-arabinitol ratio in diagnosis of invasive candidiasis in newborn infants

Infants treated in neonatal intensive care units suffer an increased risk for invasive candidiasis, but the diagnosis is sometimes difficult. D-arabinitol is a metabolite of most pathogenic Candida species. An elevated urine D-arabinitol/L-arabinitol (DA/LA) ratio is a sensitive sign of invasive candidiasis in children with cancer, but the method has not been previously evaluated for newborn infants. We therefore enrolled 117 infants in a neonatal intensive care unit, and 411 urine samples were obtained on filter paper. The DA/LA ratio was measured by gas chromatography-mass spectrometry. For 81 infants with no suspicion of superficial or invasive candidiasis, the urine DA/LA ratio was 2.7 +/- 0.7 (mean +/- standard deviation [SD]). The upper cutoff level was set at 4.8 (mean plus 3 SD). Of 22 infants with mucocutaneous candidiasis and not given systemic antifungal treatment, two had elevated DA/LA ratios, which normalized after removal of intravascular catheters. Eight other infants were given empiric antifungal treatment but had negative cultures; five of these had repeatedly elevated DA/LA ratios. Six infants with culture-positive invasive candidiasis all had one or more samples with elevated ratios. For seven infants, three with suspected and four with confirmed invasive candidiasis (for which follow-up samples were available), ratios normalized during antifungal treatment. In conclusion, urine DA/LA ratio determination is a rapid test and can be used for newborns. It is possibly more sensitive than fungal blood cultures in the diagnosis of invasive candidiasis and can also be used for monitoring the effect of antifungal treatment.     

PCR monitoring of response to liposomal amphotericin B treatment of systemic candidiasis in neutropenic mice.

When a diagnosis of invasive candidiasis has been made, treatment with toxic fungicidal agents is inevitable. The crucial decision of when to stop such treatment is difficult to make, because cultures are often negative despite ongoing invasive candidiasis and can therefore not be used as a reliable parameter of effective therapy. In the present study, the use of PCR in monitoring the therapeutic efficacy of antifungal treatment with liposomal amphotericin B was evaluated by using neutropenic mice with systemic candidiasis. Blood cultures of infected mice treated with different doses of liposomal amphotericin B were only positive at the early onset of the infection process and became sterile within 3 days; this was true even with mice treated with 1 mg of liposomal amphotericin B per kg of body weight that experienced a relapse of infection 14 days later. A significant correlation between presence of Candida albicans in the kidneys and PCR results obtained with blood was demonstrated. Thus, PCR results obtained with blood samples correlated well with the therapeutic efficacy of antifungal treatment.     

Childhood hepatic angiosarcoma--a case report

Hepatic angiosarcoma (HAS) is an extremely rare liver tumor in children. We report a case of childhood HAS in a six year old girl who presented with acute abdominal pain and fever with a mass in epigastrium. Left hepatic lobectomy was performed with a clinical diagnosis of hepatoblastoma. Histopathological examination revealed features typical of hepatic angiosarcoma. The case is presented for its rarity and to discuss the interrelation between infantile hemangioendothelioma (IHE) and HAS.     

A new long term hepatic complication in survivors of childhood haematological malignancy

Hepatic abnormalities have been documented in survivors of childhood malignancies and a spectrum of liver diseases has been described in this group The risk factors for liver disease include: hepatic surgery; radiotherapy to field including liver; total body irradiation (TBI); chemotherapy, multiple blood transfusions and use of hematopoietic cell transplantation. We report three cases of hepatic adenomatosis (HA) in young women who had been treated for haematological malignancy as children and had bone marrow transplant. These women were on estrogen and growth hormone replacement. They had mild abnormalities of liver function tests. The diagnosis of HA was made on liver imaging and confirmed by liver biopsy. We also propose a hypothesis for the pathogenesis of hepatic adenomatosis in these patients which vascular damage, estrogen replacement and growth hormone deficiency.     

Hepatic angiomyolipoma

Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm found in both males and females, and most commonly in adult females. Angiomyolipoma occurs most commonly in the kidneys. The liver represents the second most frequent site of involvement. Hepatic angiomyolipomas are composed of varying amounts of smooth muscle cells, adipose tissue, and vessels. The smooth muscle cell component is the most specific to the diagnosis. The smooth muscle cells can have varying morphologies and are positive for homatropine methylbromide-45 but are negative for hepatocyte paraffin 1 and S100 protein. The definitive diagnostic study remains the histologic examination of the surgically resected lesion coupled with immunohistochemical stains. The differential diagnosis includes hepatocellular carcinoma, hepatic adenoma, leiomyoma, hepatoblastoma, melanoma, and gastrointestinal stromal tumor. The immunohistochemical staining pattern differentiates this lesion from other malignant and benign liver lesions. If the diagnosis of hepatic angiomyolipoma has been made, it can be followed conservatively or surgically resected.     

Clinical trials using cell xenografts. Their place in the treatment of fulminant hepatitis

Trials involving xenocells are mainly carried out in the context of treatment for acute liver failure. In fact, in this disease there is no accompanying chronic hepatopathy, and the liver has a significant potential for regeneration. Regarding the clinical aspect, several trials have been conducted involving patients with severe liver failure awaiting hepatic transplantation. Hepatic xenocells are the treatment of choice, as there is no normal human hepatocyte line available. Hepatic xenocells of porcine origin are used. The experimental systems adopted in man mainly consist of extracorporal systems in which the hepatocytes are present in the extracapillary space of a capillary filter. The various systems used in man have resulted in a neurological improvement. However, the risk of PERV transmission (porcine endogenous retrovirus) remains, and is a preoccupying issue. Nevertheless, no documented case of this particular risk has yet been recorded. In conclusion, clinical trials utilizing hepatic xenocells in animals and in man are ongoing, and should permit progress to be made in the field of hepatic insufficiency.     

Systemic fungal infections in neonates

Advances in neonatal management have led to considerable improvement in newborn survival. However, early (<72 hours) and late (>72 hours) onset systemic infections, both bacterial and fungal, remain a devastating complication and an important cause of morbidity and mortality in these babies. Most neonatal fungal infections are due to Candida species, particularly Candida albicans. The sources of candidiasis in NICU are often endogenous following colonization of the babies with fungi. About 10% of these babies get colonized in first week of life and up to 64% babies get colonized by 4 weeks of hospital stay. Disseminated candidiasis presents like bacterial sepsis and can involve multiple organs such as the kidneys, brain, eye, liver, spleen, bone, joints, meninges and heart. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. The diagnosis of fungemia can be made definitely only by recovering the organism from blood or other sterile bodily fluid. Amphotericin B continues to be the mainstay of therapy for systemic fungal infections but its use is limited by the risks of nephrotoxicity and hypokalemia. Newer formulations of amphotericin B, namely the liposomal and the lipid complex forms, have recently become available and have been reported to have lesser toxicity. More recently Indian liposomal Amphotericin B derived from neutral lipids (L-Amp-LRC-1) has shown good response with less toxicity. A clinical trial with this preparation has shown to be safe and efficacious in neonatal fungal infections. Compared to other liposomal preparations, L-Amp-LRC-1 is effective at lower dose and is less expensive drug for the treatment of neonatal candidiasis.     

Clinical aspects of venous thrombophilia

Venous thrombophilia is the result of clotting changes namely of a hypercoagulable state together with blood flow and vessel wall changes. There is no need for all these components to be present in order for thrombosis to occur. As the matter of fact, thrombosis may occur even if only one of these conditions is present. In clinical practice a combination of factors is usualy seen. In comparison with arterial thrombophilia, clotting changes and blood flow seen to play a major role in venous thrombosis. Venous thrombophilia may remain asynptomatic or may result in a series of clinical syndromes. The commonest of these are: 1. Superficial vein thrombosis, 2. Deep vein thrombosis of legs, 3. Deep vein thrombosis of arms, 4. Caval veins thrombosis, 5. Portal vein thrombosis, 6. Hepatic veins thrombosis, 7. Renal vein thrombosis, 8. Cerebral sinuses thrombosis, 9. Right heart thrombosis, 10. Miscellaneous (ovarian, adrenal veins thrombosis, etc.). Since the first two are widely and easily recognized, these is no need for an extensive discussion. Deep vein thromboses of upper limbs are not as frequent as those of lower limbs or of superficial phlebitis but they can still be recognized on clinical grounds and non invasive techniques. The remaining 7 syndromes are less common and therefore less frequently suspected and recognized. Of particular interest, among these less common manifestations of venous thrombophilia are hepatic vein and renal vein thrombosis. Hepatic veins thrombosis, sometimes part of inferior vena cava thrombosis is most frequently due to an isolated occlusion of hepatic veins thereby causing a form of venocclusive disease. Occasionally diagnosis may be difficult because of slow onset of symptoms (hepatomegaly, right flank pain, fever, ascites etc.). The same is true for renal vein thrombosis which may also be of difficult diagnosis since it causes proteinuria and flank pain. The proteinuria is often interpreted as due to a nephrotic syndrome which, incidentally, may cause by its turn renal vein thrombosis. Portal vein thrombosis and cerebral sinuses thrombosis on the contrary are more easily suspected because of ascites, adominal pain, jaundice or headache, eye proptosis, vomiting. Right heart thrombosis should be suspected in cases of recurrent pulmonary embolization. Ovarian or adrenal veins thrombosis are rare. The competent physician should always consider, given certain congenital or acquired conditions, the possibility to be facing a special form of venous thrombosis or a venous thrombosis in unusual sites. An early diagnosis, as often in medicine, is of paramount importance for a prompt treatment and a satisfactory outcome.     

Biological diagnosis of systemic candidiasis: difficulties and future prospects

The diagnosis of systemic Candidiasis is difficult to establish and biologic diagnosis raises problems. Blood culture which is the gold standard for the diagnosis of systemic Candidiasis lacks sensitivity and usually takes several days to become positive. Early diagnostic approach is imperative to avoid delays in the initiation for treatment. Therefore, nonculture methods like test for Candida antigen detection, metabolite detection or Candida DNA detection by PCR are being developed for the laboratory diagnosis. Candida derived metabolites and antigens detection lacks sensitivity. A new strategy consisting of the combined detection of mannanemia and an antibody response was developed. The combined detection has a high specificity and sensitivity in the diagnosis of invasive candidiasis. The results of tests for the detection of yeast DNA by PCR obtained recently are promising in terms of sensitivity, specificity and identification of species of Candida.     

糖原累积病Ⅰa型继发肝腺瘤出血1例报道

目的 分析和总结糖原累积病Ⅰa型继发肝腺瘤破裂出血患者的临床特征。方法 对北京协和医院收治的1例糖原累积病Ⅰa型继发肝腺瘤破裂出血患者临床资料进行报道。结合文献进行分析,对肝腺瘤的概况、分型、病因、诊断及治疗方法做一总结。结果 患者为27岁男性,诊断糖原累积病14年,17岁时出现肝腺瘤,22岁时因持续腹痛、头晕就诊当地医院,诊断腺瘤内出血,行选择性肝动脉栓塞治疗。糖原累积病Ⅰa型继发肝腺瘤好发年龄为青春期,肝腺瘤并发症之一为出血,通过超声、CT等影像学检查可协助诊断,治疗方法多种,包括观察、选择性肝动脉栓塞、射频消融、手术切除、肝移植等。结论 糖原累积病Ⅰa型是一种常染色体隐性遗传病,严重肝腺瘤破裂出血可危及生命,保留通过影像学监测及早发现肝腺瘤并且适当干预可以提高患者的生活治疗,改善预后。     

The usefulness of the Platelia Candida antigen in a patient with acute lymphocytic leukemia and chronic disseminated candidiasis.

We report a protracted course of disseminated candidiasis due to Candida tropicalis in a 17-year-old man with acute lymphocytic leukemia. Despite adequate antifungal therapy (amphotericin B), C. tropicalis was recovered from biopsy specimens 25 days (skin) and 109 days (kidney) after the first positive blood cultures. While blood cultures became negative for C. tropicalis 11 days after the initiation of treatment, mannanemia persisted and became negative only after 130 days of antifungal therapy. Thus, antigen assays provided indicators of antifungal response. Differential diagnosis was difficult for this patient with the observation of persistent lesions in image studies. With positive results of antigen assays, an invasive procedure might be avoided and preemptive antifungal treatment could be initiated in a timely manner. Anti-mannan antibody remained undetectable up to 164 days after first positive blood culture despite the patient's recovery from neutropenia and recruitment of neutrophils in the tissue (skin).     

A case of the esophageal candidiasis supposedly caused by rhinenchysis steroid chronic administration before sleep]

In general, steroid is mainly used as anti-inflammatory action in case of allergic diseases. As one of the side effects of inhalation steroid, a report is given below regarding buccal capsule/esophageal candidiasis. The patient came to the hospital with the chief complaint regarding passage dysphagia in the time of deglutition; pharyngitis and esophageal candidiasis were found by endoscopy of upper gastrointestinal tract.The interview after the endoscopy revealed that the patient, a 69-year-old female was diagnosed as chronic perennial allergic rhinitis a few years ago, and had been inhaling rhinenchysis Beclometasone dipropionate (BDP) before sleep every day for the past two years because using this collunarium seemed to mitigate the nasal obstruction and mucus during sleep. The patient did not report this fact before the endocsopy because she did not associate it with her subjective symptom. In this case, it was assumed that nebulized rhinenchysis BDP was accidentally swallowed to the pharynx and esophagus during sleep. As a treatment, rhinenchysis BDP was canceled and instead Azunol mouth washing (gargling/nasal douche) was used. No antifungal agent was used. In two weeks, the patient reported some improvement, and this was confirmed by reexamination of the upper gastrointestinal tract using endoscope in one month and a half. Pharyngitis was improved, and in the digital endoscopic assessment of esophageal candidiasis complicating inhaled steroid therapy the esophageal candidiasis became Grade I (mild grade). As for the later progress, the patient did not report any subjective symptoms such as nasal obstruction and dysphagia. In addition, the inflammation caused by candidiasis and found in the early examination was improved. The patient in this case was under treatment for thrombosis in the vein of lower extremity, but no complications such as diabetes mellitus or immune deficiency syndrome were observed. DISCUSSION: Esophageal candidiasis by chronic administration of inhalation of steroid before sleep for asthmatic patients has been reported. However, there has not been a report of esophageal candidiasis by chronic administration of rhinenchysis steroid before sleep for patients with allergic rhinitis. Similarly, in the case of the use of steroid in the form of collunarium before sleep, steroid stayed in the esophagus via the transendothelial nasal cavity, and that seemed to cause, in the long run, to develop esophageal candidiasis. CONCLUSIONS: One of the implications of the above case is that collunarium can go down, even when it is nebulized in the nasal cavity, to the esophagus via the nasal cavity to buccal capsule. This suggests the necessity for preventative measures in the case of chronic administration of steroid as follows. A. Blowing of the nose just after the use of collunarium B. Daily rinsing (gargling and nasal douche).     

Hepatic mesenchymal hamartoma: a short review

Hepatic mesenchymal hamartoma is a hamartomatous growth of mesenchymal tissue in the liver of uncertain etiology. It is a space-occupying lesion that can potentially compress adjacent organs resulting in various complications including death. Hepatic mesenchymal hamartoma is characterized by proliferation of variably myxomatous mesenchyme and malformed bile ducts. The differential diagnosis includes other pediatric hepatic masses. The diagnosis is typically made during infancy, and complete resection is invariably curative.     

Malignant hepatic epithelioid hemangioendothelioma with abdominal pain due to rapid progression

Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor. We report on a patient who underwent hepatectomy for malignant HEH associated with abdominal pain due to rapid progression. An 83-year-old man was admitted to Nippon Medical School Hospital because of acute, severe upper abdominal pain. Seven months before admission, a hepatic tumor, 3 cm in diameter, had been detected in the left lateral sector. The diagnosis was hepatic cavernous hemangioma. Abdominal ultrasonography revealed a heterogeneous hyperechoic tumor with a smooth border, 6 cm in diameter, in the left lateral sector (segment 3). Contrast-enhanced computed tomography of the abdomen showed that the tumor was enhanced from the early to the late phase. Abdominal angiography revealed a cotton wool-like appearance of the tumor. The diagnosis was hepatic cavernous hemangioma. A malignancy could not be ruled out because of the tumor's rapid growth, which had caused abdominal pain. Left hepatectomy was performed. Histopathological examination showed necrosis throughout the tumor. Slightly pleomorphic neoplastic cells with rounded, spindle-like nuclei and scant cytoplasm were sporadically found in vascular channels. Intracytoplasmic lumina occasionally contained red cells. Neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34. The Mib-1 index was high. The tumor was diagnosed as malignant HEH. The postsurgical course was uneventful, and the patient was discharged on postoperative day 11. After 3 months, multiple metastatic tumors appeared in right hepatic lobe. Transcatheter arterial chemoembolization was performed.     

The diagnosis of hepatosplenic candidiasis by DNA analysis of tissue biopsy and serum

Hepatosplenic candidiasis is traditionally diagnosed by blood culture, magnetic resonance imaging (MRI), and histological analysis. The limitations of these methods include: low sensitivity (blood culture) and failure to isolate the organism (MRI/histology). This report describes a case of hepatosplenic candidiasis diagnosed by simultaneous polymerase chain reaction (PCR) analysis of liver biopsy and serum. PCR of biopsy and/or serum may offer a sensitive and specific diagnostic test for hepatosplenic candidiasis. Candida species can be identified, which helps guide antifungal chemotherapy, an important aspect in this difficult to treat infection.     

The pathology of acute hepatic disintegration in hereditary haemorrhagic telangiectasia

AIMS: Hereditary haemorrhagic telangiectasia is a rare inherited disease in which telangiectases affect skin, mucous membranes and the gastrointestinal tract. Hepatic involvement is common but usually asymptomatic. We report a case of acute hepatic disintegration in hereditary haemorrhagic telangiectasia, document the histopathological findings and present a hypothesis to explain them. METHODS AND RESULTS: The patient presented at the age of 34 years with abdominal pain, leading to the surgical removal of a severely inflamed gallbladder. Signs of liver damage became increasingly apparent over the next few weeks, with disruption of the intrahepatic biliary tree and marked vascular shunting, necessitating liver transplantation. Six months after the transplant a diagnosis of hepatic hereditary haemorrhagic telangiectasia was made. The principal features of hepatic hereditary haemorrhagic telangiectasia are periportal telangiectases and sinusoidal congestion and dilatation. Acute hepatic disintegration is characterized by disruption of liver structure, hepatocyte necrosis, haemorrhage and extravasation of bile. CONCLUSIONS: Periportal telangiectases in a liver biopsy are highly suggestive of hereditary haemorrhagic telangiectasia. Acute hepatic disintegration is likely to be a consequence of rupture of telangiectases and ischaemic necrosis of intrahepatic bile ducts. Patients with hereditary haemorrhagic telangiectasia are at risk of acute hepatic disintegration following intra-abdominal sepsis.     

Hepatic artery mycotic aneurysm of tubercular aetiology

Hepatic artery aneurysm caused by tuberculosis is extremely rare, the commonest being atherosclerosis and vasculitis. A 13 year boy admitted with suspected disseminated tuberculosis had a hepatic bruit. Patient died of aneurysmal rupture before antemortem etiological diagnosis could be established. Postmortem examination revealed widespread tubercular lesions in the chest and abdomen and hepatic artery aneurysm.     

Conversion of a neonatal hepatic hemangioma to focal nodular hyperplasia

Hepatic hemangioma and focal nodular hyperplasia are both frequently observed benign lesions of the liver. Whereas hepatic hemangioma is the most frequent benign liver tumor in children, focal nodular hyperplasia occurs predominantly in adult patients. Concomitance of both entities has been described in adults, suggesting a similar pathogenesis. We report on a 6-month-old child with a continuously shrinking hepatic hemangioma after interventional therapy and a growing hepatic mass 5 years later, which emerged as focal nodular hyperplasia at the site of the former hemangioma. Diagnostic and therapeutic strategies regarding this patient are discussed. The present case supports the theory that these two entities may share a similar pathomechanism.     

Detection of circulating candida enolase by immunoassay in patients with cancer and invasive candidiasis

BACKGROUND. Invasive candidiasis is a major nosocomial infection that is difficult to diagnose. Few biochemically defined markers of invasive candidiasis are known. Initial findings suggested that the presence of candida enolase in the blood may be a novel marker for invasive candidiasis. METHODS. We tested 170 patients at high risk for invasive candidiasis for candida enolase antigenemia. All the patients had cancer and neutropenia. We detected antigen using a double-sandwich liposomal immunoassay for candida enolase in serially collected serum samples. Invasive candidiasis was proved by finding candida species in deep nonmucosal tissue, blood cultures, or both. Antigen testing was performed with the investigator blinded to tissue or culture diagnosis. RESULTS. Among 24 patients with proved invasive candidiasis, 149 serum samples were tested for enolase antigenemia; 80 were positive and 69 negative (sensitivity per sample, 54 percent). Multiple sampling improved the detection of antigenemia, which was found in 11 of 13 proved cases of deep tissue infection (85 percent) and in 7 of 11 proved cases of fungemia (64 percent). Specificity was 96 percent as measured against control groups including patients with mucosal colonization, bacteremia, and other deep mycoses. Antigenemia was detected in the absence of fungemia in 5 cases of deep tissue candidiasis, but was not detected in 6 cases of fungemia alone. CONCLUSIONS. Candida enolase antigenemia is a novel marker for invasive candidiasis. It may be a useful indicator of deep infection in patients with cancer and neutropenia and may complement the diagnostic usefulness of blood cultures.     

Langerhans-Zell-Histiozytose der Leber

We report on the difficult differential diagnosis of liver involvement in disseminated Langerhans' cell histiocytosis (LCH). Three years after treatment of LCH involving the skull and pelvic bones, an 18-year-old girl presented with abdominal pain and cholestatic liver disease. At this time, liver biopsy showed portal infiltrates which were diagnosed as chronic non-suppurative destructive cholangitis. Two years later, she was icteric under progredient hepatic failure. A second liver biopsy revealed biliary fibrosis and granulomatous inflammation with destruction of the portal bile ducts. The morphological changes in both liver biopsies could be identified as LCH by immunohistochemical detection of CD1a and S-100-positive Langerhans' cells. Morphological changes and clinical findings in LCH of the liver may resemble primary sclerosing cholangitis or chronic non-suppurative destructive cholangitis. Therefore, LCH is an important differential diagnosis of chronic destructive cholangitis with cholestatic liver disease, especially in children and young adults. The diagnosis can be verified by S-100 and CD1a immunohistochemistry.