Validation of the standardization framework SSTR-RADS 1.0 for neuroendocrine tumors using the novel SSTR­targeting peptide [18F]SiTATE.

OBJECTIVES: Somatostatin receptor positron emission tomography/computed tomography (SSTR-PET/CT) using [68Ga]-labeled tracers is a widely used imaging modality for neuroendocrine tumors (NET). Recently, [18F]SiTATE, a SiFAlin tagged [Tyr3]-octreotate (TATE) PET tracer, has shown great potential due to favorable clinical characteristics. We aimed to evaluate the reproducibility of Somatostatin Receptor-Reporting and Data System 1.0 (SSTR-RADS 1.0) for structured interpretation and treatment planning of NET using [18F]SiTATE. METHODS: Four readers assessed [18F]SiTATE-PET/CT of 95 patients according to the SSTR-RADS 1.0 criteria at two different time points. Each reader evaluated up to five target lesions per scan. The overall scan score and the decision on peptide receptor radionuclide therapy (PRRT) were considered. Inter- and intra-reader agreement was determined using the intraclass correlation coefficient (ICC). RESULTS: The ICC analysis on the inter-reader agreement using SSTR-RADS 1.0 for identical target lesions (ICC ≥ 85%), overall scan score (ICC ≥ 90%), and the decision to recommend PRRT (ICC ≥ 85%) showed excellent agreement. However, significant differences were observed in recommending PRRT among experienced readers (ER) (p = 0.020) and inexperienced readers (IR) (p = 0.004). Compartment-based analysis demonstrated good to excellent inter-reader agreement for most organs (ICC ≥ 74%), except for lymph nodes (ICC ≥ 53%). CONCLUSION: SSTR-RADS 1.0 represents a highly reproducible and consistent framework system for stratifying SSTR-targeted PET/CT scans, even using the novel SSTR-ligand [18F]SiTATE. Some inter-reader variability was observed regarding the evaluation of uptake intensity prior to PRRT as well as compartment scoring of lymph nodes, indicating that those categories require special attention during further clinical validation and might be refined in a future SSTR-RADS version 1.1. CLINICAL RELEVANCE STATEMENT: SSTR-RADS 1.0 is a consistent framework for categorizing somatostatin receptor-targeted PET/CT scans when using [18F]SiTATE. The framework serves as a valuable tool for facilitating and improving the management of patients with NET. KEY POINTS: SSTR-RADS 1.0 is a valuable tool for managing patients with NET. SSTR-RADS 1.0 categorizes patients with showing strong agreement across diverse reader expertise. As an alternative to [68Ga]-labeled PET/CT in neuroendocrine tumor imaging, SSTR-RADS 1.0 reliably classifies [18F]SiTATE-PET/CT.

Stress fractures in systemic lupus erythematosus after long-term MTX use successfully treated by MTX discontinuation and individualized bone-specific therapy.

We report the case of a 64-year-old woman with systemic lupus erythematosus (SLE) and recurrent bilateral stress fractures of the calcaneus due to long-term methotrexate (MTX) use. A detailed skeletal assessment pointed to osteoporomalacia with pronounced trabecular thinning and increased bone resorption. After years of unsuccessful treatment with bisphosphonates, a combined bone-specific denosumab-teriparatide treatment was initiated, and additional belimumab treatment was started to avoid intermittent steroid usage. As these measures did not lead to a significant improvement of the bone situation, MTX was eventually discontinued. This was followed by a rapid clinical improvement. In a follow-up MRI scan after 18 months, the stress fractures had almost disappeared. Furthermore, the bone density and microarchitecture markedly improved. In conclusion, this case demonstrates that MTX discontinuation/replacement in combination with an individualized and state-of-the-art bone-specific therapy is effective in SLE patients with stress fractures after long-term MTX use.

Prospective comparison of diffusion-weighted MRI and dynamic Gd-EOB-DTPA-enhanced MRI for detection and staging of hepatic fibrosis in primary sclerosing cholangitis.

PURPOSE: To assess the diagnostic value of multiparametric magnetic resonance imaging (MRI) including dynamic Gd-EOB-DTPA-enhanced (DCE) and diffusion-weighted (DW) imaging for diagnosis and staging of hepatic fibrosis in primary sclerosing cholangitis (PSC) using transient elastography as a standard reference. MATERIAL AND METHODS: Multiparametric MRI was prospectively performed on a 3.0-Tesla scanner in 47 patients (age 43.9±14.3 years). Transient elastography derived liver stiffness measurements (LSM), DCE-MRI derived parameters (hepatocellular uptake rate (Ki), arterial (Fa), portal venous (Fv) and total (Ft) blood flow, mean transit time (MTT), and extracellular volume (Ve)) and the apparent diffusion coefficient (ADC) were calculated. Correlation and univariate analysis of variance with post hoc pairwise comparison were applied to test for differences between LSM derived fibrosis stages (F0/F1, F2/3, F4). ROC curve analysis was used as a performance measure. RESULTS: Both ADC and Ki correlated significantly with LSM (r= -0.614; p<0.001 and r= -0.368; p=0.01). The ADC significantly discriminated fibrosis stages F0/1 from F2/3 and F4 (p<0.001). Discrimination of F0/1 from F2/3 and F4 reached a sensitivity/specificity of 0.917/0.821 and 0.8/0.929, respectively. Despite significant inter-subject effect for classification of fibrosis stages, post hoc pairwise comparison was not significant for Ki (p>0.096 for F0/1 from F2/3 and F4). LSM, ADC and Ki were significantly associated with serum-based liver functional tests, disease duration and spleen volume. CONCLUSION: DW-MRI provides a higher diagnostic performance for detection of hepatic fibrosis and cirrhosis in PSC patients in comparison to Gd-EOB-DTPA-enhanced DCE-MRI. KEY POINTS: • Both ADC and hepatocellular uptake rate (Ki) correlate significantly with liver stiffness (r= -0.614; p<0.001 and r= -0.368; p=0.01). • The DCE-imaging derived quantitative parameter hepatocellular uptake rate (Ki) fails to discriminate pairwise intergroup differences of hepatic fibrosis (p>0.09). • DWI is preferable to DCE-imaging for discrimination of fibrosis stages F0/1 to F2/3 (p<0.001) and F4 (p<0.001).

Course of hepatitis C virus (HCV) RNA and HCV core antigen testing are predictors for reaching sustained virologic response in liver transplant recipients undergoing sofosbuvir treatment in a real-life setting.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with reduced graft survival in orthotopic liver transplant recipients. Treatment with the new direct-acting antivirals (DAAs) is safe and efficient, but no reliable predictive factors for sustained virologic response (SVR) have been identified so far. The HCV core antigen assay (HCV-core-Ag) is a new, inexpensive, and efficient method to detect viral antigens, but the value of this technique to predict treatment response in orthotopic liver transplantation (OLT) patients is still unclear. METHODS: All OLT patients who were treated with a sofosbuvir-based antiviral regimen at our center between March 2014 and August 2014 were included in the analysis (n = 20). HCV-core-Ag and HCV RNA (polymerase chain reaction [PCR]) were determined at each visit. Primary endpoints of this study were SVR at 4 or 12 weeks after end of treatment (SVR 4 and SVR 12). RESULTS: HCV-core-Ag tested negative after a median of 2 weeks (range 1-16 weeks) while PCR tests became negative after a median of 4 weeks (range 2-12 weeks). Time until PCR negativity and until HCV-core-Ag negativity showed a good correlation (R = 0.711, P < 0.001, Fig. ). Seventeen of 20 patients (85%) achieved SVR 12. SVR 12 was associated with a short time interval between treatment start and HCV PCR negativity (P = 0.005) or HCV-core-Ag negativity (P = 0.003, Mann-Whitney test). No severe side effects were observed. CONCLUSIONS: DAA treatment is safe and well tolerated in OLT. The time points of HCV-core-Ag loss and PCR negativity were predictors of SVR 12.

Efficacy and safety of sofosbuvir/ledipasvir for the treatment of patients with hepatitis C virus re-infection after liver transplantation.

BACKGROUND: Hepatitis C virus (HCV) infection is associated with a particularly poor outcome after liver transplantation. In December 2014, sofosbuvir/ledipasvir (SOF/LDV) fixed-dose combination (FDC) was approved for HCV genotype 1 and 4 in Europe. In orthotopic liver transplantation (OLT) recipients, the interferon-free treatment of HCV re-infection with novel direct-acting antivirals has been demonstrated to be safe and effective in clinical trials, but real-world data are missing. The aim of this study was to investigate the safety and efficacy of SOF/LDV FDC in OLT recipients in the real-life setting. METHODS: All consecutive OLT patients started on SOF/LDV FDC for 12 or 24 weeks at the University Medical Center Hamburg-Eppendorf and Medical School Hannover between October 2014 and August 2015 were retrospectively analyzed (n = 30). The primary efficacy endpoint was sustained virological response (SVR), i.e., absence of viremia 12 weeks after end of treatment (SVR 12). Liver function tests, creatinine, blood count, and HCV RNA (by polymerase chain reaction assay) were determined at each visit. RESULTS: SVR was achieved in 29/30 patients (96.67%) treated with SOF/LDV ± ribavirin (RBV) for 12 (n = 4) or 24 weeks (n = 25). Twenty-five patients (86.2%) received RBV. However, in 15 of the 25 patients, RBV administration had to be discontinued because of severe anemia (57.7%). One RBV-treated patient died of a myocardial infarction during antiviral therapy; this event was most likely not directly related to SOF/LDV. Aside from RBV-associated anemia, no severe side effects of the antiviral regimen were observed. CONCLUSION: Antiviral treatment with SOF/LDV is highly effective, safe, and well tolerated in OLT recipients. The addition of RBV often results in severe anemia, requiring dose reduction or discontinuation.

Determinants and frequency of irritable bowel syndrome in a German sample.

BACKGROUND: To date there is no study that has estimated the prevalence of irritable bowel syndrome (IBS) in Germany according to the current Rome III criteria. The aim of the present study was to investigate the prevalence of IBS in a non-clinical German sample. Furthermore, we investigated the association of IBS with socio-demographic and psychological risk factors. METHODS: Baseline data from a prospective cohort study were analysed, including the IBS Module of the Rome III Diagnostic Questionnaires and validated psychometric scales including the Patient Health Questionnaire-15 (PHQ-15), the Big Five Inventory (BFI), the Perceived Stress Questionnaire (PSQ-5), and the Whiteley-Index (WI-7). The study population was compared to the German general population to appraise its representativeness. Multivariate logistic regression analyses were performed to identify possible risk factors associated with IBS. RESULTS: Between January 2011 and September 2012, 2419 persons participated (female 54.0 %, mean age 37.4 ±â€Š14.9 years). According to the Rome III criteria, 401 participants (16.6 %) suffered from IBS. Five predictors were independently associated with IBS: previous traveller's diarrhoea infection (OR = 1.76; 95 % CI = 1.34 to 2.31), higher somatic symptom burden (OR = 1.15; 95 % CI = 1.07 to 1.23), increased level of hypochondriasis (OR = 2.04; 95 % CI = 1.54 to 2.70), increased vulnerability to diarrhoea under stress (OR = 3.88; 95 % CI = 3.21 to 4.68) and perceived stress (OR = 1.43; 95 % CI = 1.04 to 1.99). CONCLUSIONS: Our analyses yielded a relatively high IBS prevalence estimate, compared to studies published more than ten years ago. This might partially be explained by the fact that the time criterion of the Rome III criteria (at least 3 days/month in last 3 months) is more inclusive compared to the time criterion of the Rome II criteria (at least 12 weeks, which need not be consecutive, in the preceding 12 months).

[Multiple abscesses after a cruise along the Latin American coast]. / Multiple Abszesse nach Südamerikakreuzfahrt.

We report a case of an extracutaneous involvement of pyoderma gangrenosum. The patient initially presented with multiple sterile abscesses of the skin, heart, prostate, and kidney. Extracutaneous involvement in pyoderma gangrenosum is very rare. Confirmation of the diagnosis was only possible after exclusion of other relevant differential diagnoses. Continuous search for microbes proved negative and after an empiric therapeutic attempt with prednisolone, the patient improved quickly. However, each time we reduced the steroids even in combination with methotrexate or with azathioprine the patient relapsed. Only after therapy with the tumor necrosis factor-α-inhibitor infliximab was permanent remission achieved.

Relevance of chronic hepatitis E in liver transplant recipients: a real-life setting.

The chronic course of hepatitis E virus (HEV) infections in orthotopic liver transplant (OLT) recipients has been described previously, but prospectively collected data are rare. We aimed to study the role of chronic hepatitis E in OLT in a real-life setting. Therefore, 287 adult OLT recipients (169 male [59%], median age 56 years) were prospectively tested by HEV polymerase chain reaction assay (lower level of detection = 10 IU/mL), irrespective of their level of liver enzymes. In 4 patients (1.4%), chronic HEV infection was diagnosed. All 4 patients were male, and their age (median 48.5 years), the time since transplantation (median 45.5 months), and bilirubin level (median 0.6 mg/dL) did not differ significantly from the total cohort. However, alanine transaminase and aspartame transaminase levels were significantly higher in HEV-infected patients (75-646 U/L, median 216 U/L and 68-317 U/L, median 108 U/L) than in non-infected patients (6-617 U/L, median 41 and 6-355 U/L, median 36; P = 0.004 and 0.040, Mann-Whitney test). In 3 patients, liver biopsy was performed and revealed signs of inflammation and chronic liver disease, as enlarged densely infiltrated portal tracts with mild-to-moderate interface hepatitis. All infected patients were treated with ribavirin with the starting dose adjusted to renal function (400-800 mg/day). In 2 patients, dose reduction was necessary. Transaminases normalized in all 4 patients, and all patients cleared their infection within 3 months of ribavirin treatment. However, 1 patient experienced viral relapse 12 weeks after discontinuation. Ribavirin medication was re-started and viral clearance occurred within 8 weeks and persisted. Sequence analysis of the HEV genome of this patient revealed that he was infected with an HEV variant, which recently has been shown to have a reduced response to ribavirin in cell culture. The risk of chronic HEV infections in OLT recipients in low-endemic countries should not be overestimated. No case of chronic hepatitis E was observed in patients with normal liver enzymes, indicating that general screening of all OLT recipients is not necessary. However, if chronic hepatitis E develops, it can be treated efficiently with ribavirin.

[Economic burden of Clostridium difficile enterocolitis in German hospitals based on routine DRG data]. / Ökonomische Auswirkungen einer Clostridium-difficile-Enterokolitis in deutschen Krankenhäusern auf der Basis von DRG-Kostendaten.

BACKGROUND: Clostridium difficile associated diarrhea (CDAD) is not only a increasing medical but also economical problem. METHODS: Data from the DRG project group of the German society for digestive and metabolic diseases (DGVS) were analyzed for CDAD. Out of 430,875 cases from 37 German hospitals 2,767 cases were grouped by having CDAD either as primary (PD) or secondary diagnosis (SD; likely to be from a hospital source) in an initial or recurring hospital stay (RD). For comparison non-CDAD cases from the same hospitals from that year where matched using propensity score matching. As endpoints we defined LOS (length of stay), difference of LOS to national average LOS, total costs per case and difference between costs and revenue for all three groups. RESULTS: Patients from the PD group (n = 817) showed a mean LOS of 11.2 days compared to 8.5 days for the control group, 4,132 € mean cost per case (536 € more than control) and a mean loss of -1,064 € per case compared to -636 €. In the SD group (n = 1,840) patients stayed in the hospital for 28.8 days (control: 18.1 days), had costs of 19,381 € (control: 13,082 €) and a loss of -3,442 € compared to -849 € in the control group. Recurring cases (RD; n = 110) showed a LOS of 37.3 days (control: 21.3 days), had even higher costs (20.755 € vs. 13,101 €) and higher losses (-4,196 € vs. -1,109 €). CONCLUSION: By extrapolating these findings CDAD not only harms patients but generates a yearly cost burden of 464 million € for the German healthcare system including a loss of 197 million € for German hospitals. To the authors' opinion sufficient measures against CDAD should include pre hospital risk reduction programs, introduction of effective therapeutic and hygienic strategies in hospitals as well as improvements in documentation for these cases to support further developments of the German DRG system.

Comparison of autochthonous and imported cases of hepatitis A or hepatitis E.

BACKGROUND: Hepatitis A and hepatitis E are not limited to tropical countries but are also present in industrialized countries. Both infections share similar clinical features. There is no comparative study evaluating the clinical parameters of autochthonous and imported hepatitis A virus and hepatitis E virus infections. AIMS: The aim of this study was to determine differences between autochthonous and imported hepatitis A virus (HAV) and hepatitis E virus (HEV) infections. METHODS: Medical charts of all patients at our center with acute HAV and HEV infections were analyzed retrospectively (n = 50, study period 01/2009 - 08/2013). RESULTS: Peak bilirubin (median 8.6 vs. 4.4 mg/dL, p = 0.008) and ALT levels (median 2998 vs. 1666 IU/mL, p = 0.04) were higher in patients with hepatitis A compared to hepatitis E. In comparison to autochthones hepatitis E cases, patients with imported infections had significantly higher peak values for AST, ALT, bilirubin and INR (p = 0.009, p = 0.002, p = 0.04 and p = 0.049, respectively). In HAV infection, AST levels tended to be higher in imported infections (p = 0.08). CONCLUSIONS: (i) It is not possible to differentiate certainly between acute HAV and HEV infections by clinical or biochemical parameters, however, HAV infections might be associated with more cholestasis and higher ALT values. (ii) Imported HEV infections are associated with higher transaminases, INR and bilirubin levels compared to autochthonous cases and (iii) imported HAV infections tend to be associated with higher transaminases in comparison to autochthonous cases.

[Diagnostic workup and therapy of infectious diarrhea. Current standards]. / Diagnostik und Therapie infektiöser Durchfallerkrankungen. Was ist gesichert?

Infectious diarrhea is very common; its severity ranges from uncomplicated, self-limiting courses to potentially life-threatening disease. A rapid diagnostic workup providing detailed information on the suspected pathogen should be performed only in patients at risk, analyzing one single stool sample for Salmonella, Shigella, Campylobacter, and Norovirus. In the presence of risk factors, such as a history of antibiotic exposure within the last 3 months, testing for Clostridium difficile should be performed. Immunocompetent patients do not require specific antibiotic therapy. Exceptions exist in patients with severe comorbidities, immunodeficiency, fever/SIRS, and in patients with Shigella or C. difficile infection. Empirical antibiotic treatment should be considered in patients with fever and/or bloody diarrhea and in patients at risk. In patients with traveler's diarrhea, microbiological diagnosis is required only in patients with fever, bloody diarrhea, prolonged course of disease (more than 5 days), severe clinical course with hypotension or dehydration, and during outbreaks. In these patients one single fecal sample should be collected for stool cultures of Campylobacter, Shigella, and Salmonella, as well as microscopic examination for amoebiasis and Giardiasis. The main therapeutic measure for infectious diarrhea is sufficient oral rehydration. As in community-acquired diarrhea, azithromycin or ciprofloxacin are recommended-taking into account local antimicrobial resistance in the country of travel and possible side effects.

[Development of gastrointestinal infectious diseases between 2000 and 2012]. / Entwicklung infektiöser Durchfallerkrankungen zwischen den Jahren 2000 und 2012.

BACKGROUND: Infectious gastroenterological diseases are of increasing medical and health-economic significance. METHOD: To evaluate the development of gastroenterolgical infections (GI) over the past 10 years, we have analysed the published data of the German Federal Statistics Office on GI hospital admissions between 2001 and 2011 and the data on cases of infection reported to the Robert-Koch Institute between 2001 and 2012. RESULTS: In 2011 520795 patients with infectious diarrhoea (ICD 10 A00-A09) required hospital admission. The number of coded main diagnoses alone has more than doubled from 127867 to 282199 cases per year. The increase in the group of over 65-year-old patients was particularly high. The highest increase among hospitalised patients was seen for Clostridium difficile infections (99779 cases in 2011) together with noro- and rotavirus infections, whereas the number of cases with salmonella declined. The number of hospital deaths related to infectious gastrointestinal diseases (major clinical diagnosis) rose from 401 in 2000 to 4152 in 2011. Particularly frequent were deaths coded under the ICD 10 diagnosis A04, which includes Clostridium difficile infections (CDI). DISCUSSION: In spite of the limitations due to differing data sources, reporting and recording rules, the analysed data do allow conclusions as to the development of the last 10 years. Gastrointestinal infections have not only markedly increased but also required increasing hospital capacities in gastroenterological departments. Since, with the exception of rotavirus infections, no vaccination strategies are available, these developments will have to be combatted above all by improved infectiological training for gastroenterologists.

High vaccination coverage and infection rate result in a robust SARS-CoV-2-specific immunity in the majority of liver cirrhosis and transplant patients: A single-center cross-sectional study.

BACKGROUND: In the third year of the SARS-CoV-2 pandemic, little is known about the vaccine- and infection-induced immune response in liver transplant recipients (LTR) and liver cirrhosis patients (LCP). OBJECTIVE: This cross-sectional study assessed the vaccination coverage, infection rate, and the resulting humoral and cellular SARS-CoV-2-specific immune responses in a cohort of LTR and LCP at the University Medical Center Hamburg-Eppendorf, Germany between March and May 2023. METHODS: Clinical and laboratory data from 244 consecutive patients (160 LTR and 84 LCP) were collected via chart review and a patient survey. Immune responses were determined via standard spike(S)- and nucleocapsid-protein serology and a spike-specific Interferon-gamma release assay (IGRA). RESULTS: On average, LTR and LCP were vaccinated 3.7 and 3.3 times, respectively and 59.4% of patients received ≥4 vaccinations. Altogether, 68.1% (109/160) of LTR and 70.2% (59/84) of LCP experienced a SARS-CoV-2 infection. Most infections occurred during the Omicron wave in 2022 after an average of 3.0 vaccinations. Overall, the hospitalization rate was low (<6%) in both groups. An average of 4.3 antigen contacts by vaccination and/or infection resulted in a seroconversion rate of 98.4%. However, 17.5% (28/160) of LTR and 8.3% (7/84) of LCP demonstrated only low anti-S titers (<1000 AU/ml), and 24.6% (16/65) of LTR and 20.4% (10/59) of LCP had negative or low IGRA responses. Patients with hybrid immunity (vaccination plus infection) elicited significantly higher anti-S titers compared with uninfected patients with the same number of spike antigen contacts. A total of 22.2% of patients refused additional booster vaccinations. CONCLUSION: By spring 2023, high vaccination coverage and infection rate have resulted in a robust, mostly hybrid, humoral and cellular immune response in most LTR and LCP. However, booster vaccinations with vaccines covering new variants seem advisable, especially in patients with low immune responses and risk factors for severe disease.

Autoimmune hepatitis 2013 and beyond.

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease leading to cirrhosis and its complications if left untreated. Clinical features include elevated transaminases, elevated immunoglobulin G and the presence of autoantibodies. A liver biopsy is necessary for the establishment of the diagnosis. If treated properly and timely, prognosis of AIH is excellent. Standard treatment today consists of azathioprine and prednisolone and leads to remission in the vast majority of patients. Intolerance to standard treatment or incomplete remission as well as special patient groups such as pregnant patients or elderly patients require second- or sometimes even third-line treatments. For those patients, a number of effective drugs are available off-label and induction of remission will be possible in the vast majority of patients. Choice of drug regimen is important as drug-drug-interactions, concomitant diseases, age and gender of the patients have to be taken into account to achieve a tolerable side effect profile and good quality of life in patients. Mycophenolate mofetil is the drug of first choice in azathioprine intolerance. Other treatments may include the use of cyclosporine, tacrolimus, cyclophosphamide or biologicals such as rituximab or infliximab. Close monitoring of the patients will be necessary as side effects may occur.

[Comorbidity of rheumatic and hepatic diseases]. / Komorbidität rheumatischer und hepatologischer Erkrankungen.

The correlation between rheumatic diseases and liver diseases is complex and often not given sufficient attention. There are, however, consequences for diagnosis and therapy. Rheumatic diseases can present with hepatic symptoms while liver diseases can exhibit rheumatic symptoms. Examples of liver diseases as a cause of rheumatic symptoms are viral hepatitis B and C, autoimmune hepatitis and hemochromatosis. As a result of rheumatic diseases, such as adult onset Still's disease and systemic lupus erythematosus, liver dysfunction can occur. Autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis are directly associated with rheumatic diseases and have to be distinguished by way of differential diagnosis. During antirheumatic therapy, serious hepatotoxic side effects have to be expected.

[Inflammatory diseases with liver and joint involvement. A differential diagnostic challenge]. / Inflammatorische Erkrankungen mit Leber- und Gelenkbeteiligung. Eine differenzialdiagnostische Herausforderung.

Elevated levels of liver enzymes in patients with rheumatic symptoms require a comprehensive differential diagnostic thought process. On the one hand there can be hepatic involvement of primarily rheumatological diseases but this is quite rare. Drug-induced liver injury by antirheumatic medication is more frequent. On the other hand arthralgia can be a sign of primary hepatopathy whereby hemochromatosis and autoimmune hepatitis (AIH) are typical examples. Furthermore, some liver diseases are associated with rheumatological diseases, such as primary biliary cirrhosis (PBC) and chronic hepatitis C infection (HCV). Only an exact diagnosis will lead to specific treatment which will improve the symptoms and course of disease.

[A 44-year-old woman with hereditary nonpolyposis colon carcinoma: screening examinations for non-colonic tumors]. / 44-jährige Patientin mit hereditärem nichtpolypösem Kolonkarzinom: Vorsorgeuntersuchungen nichtkolonischer Tumoren.

A 44-year-old woman presented in March 2010 for surveillance esophagogastroduodenoscopy (EGD). In October 2004, rectal cancer had been diagnosed and treated by resection of the rectum with adjuvant chemotherapy. A diagnosis of hereditary nonpolyposis colon carcinoma (HNPCC) was established on the basis of the Amsterdam II criteria. Due to a lack of clear guidelines we decided to perform annual systematic surveillance examinations of the stomach and the most frequent tumor manifestations. Until 2009, extracolonic tumors were not observed in the patient. In March 2010, EGD showed a discrete erosive lesion in the gastric antrum, which was biopsied. Most notably, the histopathological examination revealed a poorly differentiated mucinous adenocarcinoma. Due to the poor differentiation, we decided against technically possible, endoscopic resection. The patient underwent subtotal gastrectomy and is still doing fine 28 months after surgery. This case prompted us to evaluate our surveillance approach in HNPCC patients and to review the literature.

Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors.

BACKGROUND: Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. METHODS: Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. RESULTS: 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on 'liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed 'liver metastases of NET' in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2-15%. CONCLUSION: SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4-5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.