[Abdominal pain and seizure in a 26-year-old student from England]. / Abdominelle Schmerzen und Krampfanfall bei einer 26-jährigen Studentin aus England.

A 26-year-old female presented to the emergency department due to abdominal pain in spite of painkillers. After extensive clinical diagnostics, no specific cause could be found. The further course was aggravated by a seizure due to hyponatremia. The combination of abdominal and neurological symptoms as well as darkening of the urine led to the diagnosis of porphyria. Drugs that were known to be triggers were avoided and treatment with heme arginate and glucose was started. In addition, treatment of the delirium and infection led to a complete remission of symptoms.

[Porphyrias-what is verified?] / Porphyrien ­ was ist gesichert?

Porphyrias are caused by enzyme defects of heme biosynthesis. According to their clinical presentation and to each affected pathway, they are categorized into acute and non-acute as well as hepatic and erythropoietic porphyrias. Acute hepatic porphyrias, e.g. acute intermittent porphyria (AIP), porphyria variegata (VP), hereditary coproporphyria (HCP) and 5­aminolevulinic acid dehydratase-deficient porphyria (ALADP) are characterized by accumulation of the porphyrin precursors 5­aminolevulinic acid (ALA) and porphobilinogen (PBG) that correlate with severe abdominal, psychiatric, neurological or cardiovascular symptoms. Additionally, skin photosensitivity can occur in VP and less frequently, in HCP. Decisive for the diagnosis of acute hepatic porphyrias are a >4-fold elevated urinary excretion of ALA in ALADP and ALA and PBG in all other acute porphyrias. First-line treatment of an acute porphyria attack includes intensive care with pain management, sufficient caloric supply, strict avoidance of porphyrinogenic drugs and elimination of other triggering factors. Heme therapy is indispensable in case of developing neurological symptoms and clinical worsening despite first-line measures. Non-acute porphyrias, mainly porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP) and X­linked protoporphyria (XLP) display accumulation of porphyrins in the skin and/or liver resulting in photosensitivity up to possible liver damage. Patients with PCT benefit from iron depletion, low-dose chloroquine treatment and/or hepatitis C virus elimination. Afamelanotide is associated with better sunlight tolerance in patients with EPP and XLP. Moreover, innovative therapies that highly selectively address dysregulated steps of the heme biosynthetic pathway are currently under clinical trial.

[Porphyrias]. / Porphyrien.

Porphyrias are metabolic disorders of the heme biosynthesis. Clinically, they can be differentiated into acute and non-acute porphyrias. The symptomatic phase of acute hepatic porphyrias is characterized by overproduction of neurotoxic porphyrin precursors and porphyrins. Acute intermittent porphyria, Variegate porphyria, Hereditary coproporphyria and Doss porphyria belong to this group of metabolic disorders. The clinical presentation of the acute hepatic porphyria syndrome includes abdominal, psychiatric, neurological and cardiovascular symptoms. The diagnosis is based on a tenfold increased urinary excretion of porphobilinogen (apart from Doss porphyria). Besides symptomatic therapy with non-porphyrinogenic drugs, electrolyte compensation and intensive monitoring, intravenous administration of glucose and heme arginate is established for treatment. Among the non-acute types like Porphyria cutanea tarda, Erythropoietic protoporphyria and Congenital erythropoietic porphyria, the accumulated porphyrins cause photosensitivity of the skin up to severe liver damage. The location of the deficient enzyme within the heme biosynthesic pathway determines the pattern of the accumulated porphyrins. Besides light protection, there are different therapies depending on the type of non-acute porphyria. Ultimately, liver transplantation may be considered in therapy-resistant cases of acute hepatic porphyrias and bone marrow transplantation in severe cases of erythropoietic porphyrias.

Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems?

Well differentiated neuroendocrine tumors (NETs) of the stomach (gastric carcinoid tumors) are observed more often, with a tenfold increase in the US in the last 30 - 35 years, and the prognosis has improved greatly in that time. Nowadays most carcinoids of the stomach are diagnosed at an early stage. Four types of gastric NETs have been proposed and recognition of the type is important for defining the diagnostic approach and treatment. Often gastric NETs (especially type 1) are found incidentally during a gastroscopy performed for other reasons; most of these NETs are smaller than 20 mm in size. Conservative management and endoscopic surveillance is adequate for well differentiated, multifocal gastric carcinoids (type 1 or type 2 gastric NETs) that are less than 10 - 20 mm in diameter, unless they show angioinvasion, infiltrate the muscular wall, or have a proliferation rate above 2 %. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. It is essential to distinguish between multifocal (types 1 and 2) and unifocal type 3 or type 4 gastric NETs, since surgery is indicated for type 3 gastric NETs larger than 10 mm in diameter and for poorly differentiated (localized) neuroendocrine gastric carcinomas (type 4 gastric NET). For optimal management, the type, biology, and stage of the tumor as well as the individual situation of the patient must be considered. Most patients with well differentiated gastric NETs can be treated conservatively and be followed up with endoscopic surveillance.

[A 23-year-old patient with sore throat and cervical lymph node enlargement: a rare presentation of tularemia]. / 23-jähriger Patient mit Halsschmerzen und progredienter Lymphknotenschwellung: Eine seltene Form der Hasenpest.

We report a case of oropharyngeal tularemia--an uncommon manifestation of this disease. There is a low prevalence of tularemia in Germany. Therefore the diagnosis can be confirmed only by well directed laboratory diagnostics. Without correct antibiotic therapy mortality can reach 33%--depending on the subspecies of Francisella tularensis. For this reason tularemia should be included into the differential-diagnostic considerations in patients with unclear lymph node enlargement.

[Neuroendocrine tumors of the small bowels are on the rise: early tumors and their management]. / Neuroendokrine Tumoren des Dünndarms nehmen zu: frühe Tumoren und deren Management.

Neuroendocrine tumors (NETs) of the small bowels are on the rise: in the US they have increased by 300-500% in the last 35 years. At the same time their prognosis has been much improved. Most NETs of the duodenum are nowadays detected "incidentally" and therefore recognized at an early stage. Duodenal NETs that are well differentiated, not larger than 10 mm in greatest dimension and limited to the mucosa/submucosa can be endoscopically resected. In NETs with a size between 10 mm and 20 mm the therapeutic strategy has to be individually discussed. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is indicated for well differentiated duodenal NETs greater than 20 mm, for localized sporadic gastrinomas and for localized poorly differentiated NE cancers. Surgery is also indicated for localized/regional ileal NETs. Advanced ileal NETs with a carcinoid syndrome are treated with stable somatostatin analogs. This treatment also significantly improves the (progression-free) survival in patients with metastatic NETs of the ileum. For optimal NET management tumor biology, type, localization and stage of the neoplasm as well as the individual situation of the patient have to be taken into account.

Safe and probably safe drugs in acute hepatic porphyria.

Acute porphyrias are caused by enzyme defects along the heme synthesis pathway. Patients usually present with abdominal pain, impaired intestinal motility, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine. This article gives an overview over drugs that are recommended in patients with acute hepatic porphyrias and represents a compilation of four so far existing lists.

[Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: good prognosis with early detection]. / (Neuro-)Endokrine Tumoren des Magens sind auf dem Vormarsch: Gute Prognose bei frühem Nachweis.

Neuroendocrine tumors (NET) of the stomach are on the rise. In the United States they have increased about tenfold in the last 35 years. Prognosis has been much improved over the last three to four decades. Nowadays most of such NETs are diagnosed at an early stage. Quite often gastric NETs are found incidentally during a gastroscopy, performed for other reasons. Most of the asymptomatic, well differentiated gastric NETs are less than 2 cm in diameter. Conservative management and endoscopic surveillance is adequate for well differentiated, multifocal type 1 or type 2 gastric NETs (gastric carcinoids) of 10-20 mm , unless they are angio-invasive, have infiltrated into the muscularis propria or have metastasized. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. Surgery is, however, indicated for all NETs larger than 20 mm. For optimal management tumor biology, type and stage of the neoplasm as well as the individual situation of the patient have to be taken into account. Most of the patients can be treated conservatively and be followed up with endoscopic surveillance.

Does chloroquine therapy of porphyria cutanea tarda influence liver pathology?

BACKGROUND: Porphyria cutanea tarda (PCT) is regularly associated with changes in liver tissue. On the other hand, systematic investigations are lacking on whether there is a correlation between the severity of liver damage and chloroquine treatment. PATIENTS AND METHODS: During a 20-year period, liver biopsies were obtained in 89 patients with PCT confirmed by biochemical analysis of urine and feces and low-dose chloroquine therapy. Seventeen patients with alcohol-induced liver disease were excluded. In 8 of 63 patients, only a single biopsy was available. Classification of liver damage was performed according to the Riedel score. Electron microscopy was available from 24 patients. In a second group of patients, the HFE status was investigated and Berlin blue stains of liver biopsies were performed. RESULTS: There was no correlation between the duration of cutaneous symptoms and liver pathology. After 12 months chloroquine treatment, 45 patients (81%) disclosed an improvement of liver pathology, nine (16%) had no change, and a worsening was observed in one patient (3%). All patients achieved a complete clinical and biochemical remission. In 13 of 16 patients with a relapse, there was again a deterioration of liver damage. Patients with HFE mutations had a significant higher risk (P < 0.05) for hepatic siderosis. CONCLUSIONS: The severity of liver damage was not correlated with the disease duration. Chloroquine treatment resulted in PCT remission (clinical and biochemical) and in 81% to an improvement of liver morphology.

[Coincidental squamous cell cancers of the esophagus, head, and neck: risk and screening]. / "Field cancerization" im oberen Aerodigestivtrakt: Uberwachungsempfehlungen für Risikopersonen.

The term "field cancerization" was coined by Slaughter in1953 when describing multifocal synchronous and metachronous carcinogenesis in the upper aerodigestive system. Patients suffering from head and neck cancer (HNC) have or develop a second esophageal squamous cell cancer (ESCC) or bronchial cancer (BC) in 5-14% of cases. When a second esophageal cancer occurs in a patient with HNC, the prognosis is generally determined by the ESCC, and, unfortunately, it is poor. Screening and surveillance by Lugol chromoesophagoscopy enable early detection and curative treatment of second esophageal neoplasias. Surveillance appears to result in a survival benefit for HNC patients. Vice versa, patients with ESCC or BC have a risk of about 10% for developing HNC. Periodic pharyngolaryngoscopy is recommended for curatively treated ESCC or BC patients. Patients with field cancerization should be surveilled by a multidisciplinary approach.

[Increased incidence of hepatocellular and intrahepatic cholangiocellular carcinoma in northeast Germany]. / Zunahme des hepatozellulären und des intrahepatischen cholangiozellulären Karzinoms im Nordosten Deutschlands.

BACKGROUND AND OBJECTIVE: Hepatocellular cancer (HCC) is one of the five most common cancers worldwide. In Western countries the incidence of both HCC and intrahepatic cholangiocellular cancer (iCCC) has increased quite dramatically in the last 20 years. It was the aim of this study to assess the epidemiological changes of both cancers in the Northeast of Germany. METHODS: Using the data base of the Joint German Cancer Registry of the New Federal States and of Berlin, the age- and world-population-adjusted incidence of HCC and iCCC and their 5-year survival were calculated. The states of Brandenburg, Mecklenburg-Vorpommern and Saxony were chosen for this study because of the high quality of their registration base. RESULTS: In men the age-adjusted incidence of HCC increased from 3.6 in 1976 to 5.7 in 2002, the absolute number of newly diagnosed HCCs rising from 192 to 383 males within this period. In women the incidence was much lower. While only 30 males and 36 females were diagnosed with iCCC in 1976, in 2002 there were 64 men and 75 women with iCCC. In 1976, the corresponding age-adjusted incidence was 0.5 in men and 0.4 in women. Up to 2002 the incidence of iCCC rose to 0.8 and 0.6, respectively. The cumulative 5-year survival of HCC and iCCC was less than 10% for each. Comparison of the early period (1978-1979) with the later one (1998-1999) demonstrated a statistically significant improvement in survival for HCC. This was most likely due to earlier diagnosis and treatment of HCC. CONCLUSION: In the Northeast of Germany the incidence of both HCC and iCCC have increased markedly in the last 20 years. The recently improved survival of HCC patients most likely reflects earlier diagnosis and treatment.

[Hepatitis C, hemochromatosis and porphyria cutanea tarda]. / Hepatitis C und Hämochromatose bei Porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) is characterized by decreased activity of the enzyme uroporphyrinogen decarboxylase (URO-D) and the accumulation of uro- and heptaporphyrins in the liver. Apart from increased alcohol exposure and certain drugs, PCT is associated with antibodies to the hepatitis C virus (HCV), with its prevalence increasing from Northern (8-10%) to Southern Europe (71 to 91%). Chronic HCV-infection is thus considered to be a major trigger for PCT and PCT is said to be an important extrahepatic manifestation of HCV-infection in predisposed individuals. Iron overload is common in PCT. Iron is an inhibitory co-factor of URO-D activity in hepatocytes. Accordingly, in support of the critical role of iron, the clinical efficacy of iron removal is coupled to an improvement of hepatic URO-D activities. Up to two thirds of Saxon patients with PCT carry the classical hemochromatosis (HFE) mutations (C282Y and/or H63D). HFE genotyping can help to further classify patients with PCT and associated hemochromatosis. Simple or compound heterozygosity of HFE mutations does not affect the therapeutic response to chloroquine in PCT. Since Patients carrying homozygous mutations (C282Y/C282Y) with hemochromatosis and PCT do not respond to chloroquine, phlebotomy should be first-line treatment to remove toxic iron.

Low prevalence of chronic hepatitis C, but high prevalence of elevated aminotransferases in a cohort of 2026 patients referred for orthopaedic surgery in the eastern part of Germany.

INTRODUCTION: The prevalence of chronic hepatitis C in Germany is about 0.2 - 0.4 %. However, there seems to be regional differences between western and eastern states of the country. Thus, the present study analysed the prevalence of chronic hepatitis C in a cohort of orthopaedic patients in Thuringia. METHODS: Tests for antibodies against hepatitis C virus (anti-HCV) were performed on serum samples of 2026 patients (1183 females, 843 males) admitted for orthopaedic surgery to a university hospital in Thuringia. If anti-HCV was positive, serum was tested for HCV-RNA by polymerase chain reaction (PCR). For the sake of anonymity only age and gender were reported in all patients. In 1465 cases, values of alanine (ALT) and aspartate (AST) aminotransferases were additionally available. The low HCV prevalence was confirmed in a second cohort of orthopaedic patients (n = 929, 599 females, 330 males) investigated at a university hospital in Saxonia. RESULTS: In the Thuringian cohort, anti-HCV was detectable in 12/2026 (0.6 %) individuals (10 females (0.85 %) and 2 males (0.24 %: p = 0.14 %). HCV-RNA was positive in 3/10 of anti-HCV positive females (0.15 % of the study cohort). HCV infection was already known in two cases. Anti-HCV positive patients seemed to be older than anti-HCV negative individuals (64.25 vs. 59.48 years; p = 0.17), as well as HCV-RNA positive cases compared to non-viraemic patients (66.3 vs. 63.6 years; p = 0.32). All HCV-RNA positive females had elevated ALT values. However, ALT and AST were also elevated in 18.2 % and 11.7 % of anti-HCV negative individuals. There was no significant difference between males and females (p = 0.32). In the Saxonian cohort none of 929 individuals were HCV positive. CONCLUSION: The prevalence of chronic hepatitis C is low in the investigated cohorts of orthopaedic patients in Thuringia and Saxonia. However, elevation of aminotransferases occurs surprisingly often. The reasons for elevated aminotransferases and a reliable analysis of the HCV prevalence in different subgroups of the Eastern German population require further evaluation.

C282Y and H63D mutation of the hemochromatosis gene in German porphyria cutanea tarda patients.

BACKGROUND AND AIMS: Patients with porphyria cutanea tarda (PCT) have a susceptibility to reversible inactivation of hepatocyte uroporphyrinogen decarboxylase, which can be triggered by alcohol, hepatitis C virus, and other agents. Inherited factors that may predispose to PCT include the C282Y mutation in the hemochromatosis (HFE) gene. METHODS: We analyzed the hemochromatosis mutations C282Y and H63D in liver biopsies and serum samples of 190 German patients (mean age 48+/-12.5 years) with sporadic PCT. The hepatic iron concentration was determined within the liver tissue. Age-matched healthy blood donors (115 donors) served as controls. RESULTS: The C282Y and H63D mutations were found in 75 (39%) and 85 (45%) of 190 patients with PCT, respectively. Twenty-two patients (12%) were homozygous for the C282Y mutation, and eighteen patients (9%) were compound heterozygotes, displaying both the C282Y and the H63D mutation. Within the control group, 3 of 115 patients were heterozygous for C282Y (3%) and 12 for H63D (10%). Serum and hepatic iron, ferritin, transferrin saturation, or liver enzymes did not differ significantly between patients with or without HFE mutations. CONCLUSIONS: The high frequency of homo- and heterozygosity for the C282Y and H63D alleles strongly suggests that these mutations are important predisposing factors for PCT in German patients.