[Whether or not to perform an early endoscopy following ingestion of potentially caustic agents - a retrospective longterm analysis in a tertiary referral institution]. / Wann sollte eine frühe endoskopische Inspektion bei Verletzungen des oberen Gastrointestinaltrakts nach Ingestion von potenziell ätzenden Substanzen und anderen Noxen erfolgen? - Eine retrospektive 13-Jahres-Analyse in einem tertiären Haus der Maximalversorgung.

BACKGROUND: The optimal clinical management of patients following ingestion of potentially caustic lesions is still undetermined. In particular, the indication for early upper GI endoscopy in this context remains unclear. PURPOSE: To draft recommendations regarding the use of early upper GI endoscopy following hospital admissions of patients after ingestion of potentially caustic agents. METHODS: For this purpose, a retrospective cohort study of patients treated for ingestion of potentially caustic substances during a 13 year-period at the university hospital of Berne was performed. RESULTS: In total, 61 patients with acute ingestion of potentially caustic substances were identified. Overall mortality was 5 %. 11/61 patients had to be admitted to the intensive care unit. Most ingestions were performed in suicidal intention (62 %). In 53 % of these patients, a combined ingestion of several substances occurred. In 33 % of patients, an early upper GI endoscopy was performed within 24 hours after ingestion. The degree of burn depended upon the hazard potential of the respective substance. In patients with ingestion of low risk substances, upper GI endoscopy was only performed when additional risk factors were present. CONCLUSION: Based upon the results of the present study, ingestion of potentially caustic agents requires an individualized strategy whether or not to perform early endoscopy.

Determination of intrarenal resistance index (RI) in patients with multiple myeloma.

BACKGROUND: Renal impairment is a common complication of multiple myeloma occurring in up to 50 % of patients at some stage in their disease. Due to occurrence of cast nephropathies we hypothesized circulatory dysregulation (vasoconstriction) in the kidneys with measurable elevation of the resistance index among these patients which would have a diagnostic impact. SUBJECTS AND METHODS: 36 patients with treated multiple myeloma (21 females, 15 males, mean age 61.6 +/- 8.5 years) were prospectively examined by conventional abdominal ultrasound with focussed investigation of the kidneys. First, length of the organs, parenchymal width and characterization of parenchymal echogenicity were determined. Then, intrarenal RI values were measured in segmental and arcuate arteries, respectively, in both kidneys. Additionally, serum creatinine, BUN and GFR of each patient were evaluated. RI values were compared to values of 78 healthy control subjects. RESULTS: Mean renal RI was 0.68 +/- 0.07 which was slightly higher than in controls with 0.62 +/- 0.05, but without statistical significance. Due to the laboratory analyses patients were subdivided in those with normal ( group 1, n = 21) and those with impaired (group 2, n = 15) renal function. In both groups kidney size and parenchymal width were normal. Significant more group 2 patients (60%) revealed hyperechogenic parenchyma than group 1 patients (24%) (p<0.01). Mean renal RI indices were 0.67 +/- 0.06 (right) and 0.69 +/- 0.06 (left) in group 1 patients and 0.71 +/- 0.08 (right) and 0.71 +/- 0.07 (left) in group 2 patients and showed no significant difference (p = 0.06 and 0.15). CONCLUSION: Renal RI values are not significantly elevated in patients with multiple myeloma even in those with renal impairment so that no hints to a relevant vasoconstriction could be evaluated. RI seems not to be a relevant parameter for the diagnosis of cast nephropathy of multiple myeloma patients. Routinely performed ultrasound examination should be more focussed on the qualification of parenchymal echogenicity.

Acute pancreatitis and thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) has multiple clinical manifestations and risk factors, but the events that actually trigger acute episodes of TTP are often unclear. We describe the case of a 56-year-old woman who presented with clinical signs and symptoms of TTP and acute pancreatitis. We discuss whether pancreatitis was due to ischemic pancreatic damage caused by microvascular platelet clumping in the frame of TTP, or whether acute pancreatitis, a disorder that results in an intense systemic inflammatory response, may be a triggering event for acute episodes of TTP.

Intrarenal resistance index for the assessment of early renal function impairment in patients with liver cirrhosis.

BACKGROUND: Renovascular vasoconstriction in patients with hepatorenal syndrome can be quantified by the renal arterial resistance index (RI). We investigated the value of RI measurement in detection of renal function impairment in patients with different stages of chronic liver disease. METHODS: Subjects were divided into 4 groups containing 21 patients with liver cirrhosis and ascites, 25 patients with liver cirrhosis without ascites, 35 patients with fatty liver disease and 78 control subjects. All patients underwent abdominal ultrasound examination with renal RI measurement and correlation with laboratory results for renal function. RESULTS: RI was significantly higher in ascitic patients compared to non-ascitic patients (0.74 vs. 0.67, p<0.01) and in non-ascitic patients with liver cirrhosis than in control subjects (0.67 vs. 0.62, p<0.01). 48% (19/40) of patients with liver cirrhosis and normal serum creatinine concentration showed elevated RI levels. There were no significant differences in RI levels between patients with fatty liver disease and controls (0.63 vs. 0.62). CONCLUSIONS: Intrarenal RI measurement is a predictor of renal vasoconstriction and serves to detect early renal function impairment in cirrhotic patients. The diagnosis of elevated RI may be taken into account in the clinical management of these patients.

Advanced Lemierre syndrome requiring surgery.

A 38-year-old homeless man was admitted with a 2-week history of a sore throat, increasing shortness of breath, and high fever. Clinical examination showed enlarged and tender submandibular and anterior cervical lymph nodes and a pronounced enlargement of the left peritonsillar region (Figure 1a). CT scan of the throat and the chest showed left peritonsillar abscess formation, occlusion of the left internal jugular vein with inflammatory wall thickening and perijugular soft tissue infiltration, pulmonary abscesses, and bilateral pleural effusions (Figures 1b-e, arrowed). Anaerobe blood cultures grew Fusobacterium necrophorum, leading to the diagnosis of Lemierre's syndrome. Treatment with high-dose amoxicillin and clavulanic acid improved the oropharyngeal condition, but the patient's general status declined further, marked by dyspnea and tachypnea. Repeated CT scans showed progressive lung abscesses and bilateral pleural empyema. Bilateral tonsillectomy, ligation of the left internal jugular vein, and staged decortication of bilateral empyema were performed. Total antibiotic therapy duration was 9 weeks, including a change to peroral clindamycin. Clinical and laboratory findings had returned to normal 12 weeks after surgery.The patient's history and the clinical and radiological findings are characteristic for Lemierre's syndrome. CT scans of the neck and the chest are the diagnostic methods of choice. F. necrophorum is found in over 80% of cases of Lemierre's syndrome and confirms the diagnosis. Prolonged antibiotic therapy is usually sufficient, but in selected patients, a surgical intervention may be necessary. Reported mortality rates are high, but in surviving patients, the recovery of pulmonary function is usually good.

Recurrent ischemic colitis in a patient with leiden factor V mutation and systemic lupus erythematous with antiphospholipid syndrome.

Ischemic colitis results from insufficient blood supply to the large intestine and is often associated with hypercoagulable states. The condition comprises a wide range presenting with mild to fulminant forms. Diagnosis remains difficult because these patients may present with non-specific abdominal symptoms. We report a 51- year-old female patient with known Leiden factor V mutation as well as systemic lupus erythematous along with antiphospholipid syndrome suffering from recurrent ischemic colitis. At admission, the patient complained about abdominal pain, diarrhea and rectal bleeding lasting for 24 hours. Laboratory tests showed an increased C-reactive protein (29.5 mg/dl), while the performed abdominal CT-scan revealed only a dilatation of the descending colon along with a thickening of the bowel wall. Laparotomy was performed showing an ischemic colon and massive peritonitis. Histological examination proved the suspected ischemic colitis. Consecutively, an anti-coagulation therapy with coumarin and aspirin 100 was initiated. Up to the time point of a follow up examination no further ischemic events had occurred. This case illustrates well the non-specific clinical presentation of ischemic colitis. A high index of suspicion, recognition of risk factors and a history of non-specific abdominal symptoms should alert the clinicians to the possibility of ischemic disease. Early diagnosis and initiation of anticoagulation therapy or surgical intervention in case of peritonitis are the major goals of therapy.

[Acute headache in a case of cerebral cavernomas]. / Akute Kopfschmerzen bei zerebralen Kavernomen.

We report a case of a 52-year-old female patient with known cerebral cavernomas and acute headache. A cranial CT scan excluded an intracranial bleeding. Cavernomas are rare vascular malformations of the venous blood system (synon. cavernous angiomas) with a slow blood flow. Clinical manifestation is presented between an age of 30-50 years with mostly unspecific neurological symptoms like headache, nausea, vomiting and dizziness, but also epileptic seizures and bleedings may occur. In general, therapy is symptomatic. In cases of seizures, however, anticonvulsive treatment is indicated. Operation can be discussed for peripheral localized cavernomas with bleeding or for refractory seizures. If antiplatelet or anticoagulation therapy is necessary due to other diseases (coronary heart disease, atrial fibrillation, thrombosis, pulmonary embolism), cerebral cavernomas are not considered as an absolute contraindication. The risk for an ischemic stroke under atrial fibrillation (5-20%), for example, is higher than the risk for bleeding of a cerebral cavernoma under anticoagulation therapy.

Age dependency of intrarenal resistance index (RI) in healthy adults and patients with fatty liver disease.

BACKGROUND: Our aim was to investigate the influence of age and gender on intrarenal resistance index (RI) measurements in 78 healthy subjects (46 males, 32 females; group 1) and 35 subjects (group 2) with fatty liver disease (28 males and 7 females). SUBJECTS AND METHODS: First, each subject underwent a conventional abdominal ultrasound examination. Then, intrarenal RI values were determined from three distinct interlobar and cortical arteries respectively on both kidneys. The correlation of intrarenal RI with age and gender as a variable was statistically evaluated by linear regression. RESULTS: In group 1, the variables gender, kidney region and comparison of right versus left kidney had no significant effect on intrarenal RI (p>0.05). The variable age, on the other hand, showed a significant positive correlation on all four defined measuring points (p<0.01) with linear correlation coefficients of r = 0.26 (left kidney, central) to r = 0.37 (right kidney, cortical). Therefore normal RI values at ages 25, 45, 65 years could be defined as 0.59, 0.61 and 0.63, respectively. Age dependency can thus be expressed as a function with the formula y = 0.565 + 0.001.x. Patients with fatty liver disease showed age dependency on renal RI (p<0.01) as well. CONCLUSION: In accordance with other studies, the influence of age on intrarenal RI measurement is significant in healthy subjects. Intrarenal RI values from subjects with a fatty liver disease showed age dependency as well. Therefore it is necessary to consider the age of the examined person to interpret RI values correctly.

[Alternative sonographic determination of liver size by intercostal scans]. / Alternative sonographische Bestimmung der Lebergrösse durch interkostale Schnittführung.

BACKGROUND: The evaluation of hepatic size is a daily question in abdominal ultrasound, especially to determine the presence of hepatomegaly. In the literature, different methods of measurement are described, mostly as a subcostal measured organ diameter in one direction. This method has its limits in patients with obesity, accumulation of abdominal gas or in uncooperative patients (lack of coordinative respiration) so that alternative measurements are necessary. METHODS: In 241 patients hepatic size was first measured in two conventional sections: midclavicular line (MCL) and anterior axillary line (AAL). Additionally, we measured the organs in midaxillary line craniocaudal (MAL) by determination of the cranio-caudal diameter. In 58 patients additional computed tomography was performed due to special diagnostical reasons so that liver size in MCL could be revealed and compared with ultrasonographical values. RESULTS: The mean value in MCL was 10.7 +/- 2.1 cm measured by ultrasound, 11.4 +/- 3.7 cm measured by computed tomography, 14.0 +/- 1.9 cm in AAL and 14.9 +/- 2.0 cm in MAL. In 5% of the cases the liver could not be measured in the conventional subcostal sections due to obesity or masking by gas, but this was possible in MAL. CONCLUSIONS: We revealed a good correlation of liver size in MCL between ultrasound and computed tomography, as well as in the measurement of AAL and MAL diameters. However, even in cases with difficult subcostal approach intercostal diameters allow for an accurate determination of hepatic size.

[Eosinophilia, diarrhea and asthma in a young woman]. / Eosinophilie, Diarrhoe und Asthma bei einer jungen Frau.

We present the case of a young woman that was diagnosed with Churg-Strauss syndrome. The classical as well as the atypical symptoms, signs and findings are discussed in the context of clinically relevant differential diagnoses. The diagnostic criteria and the relevant aspects of pathogenesis, clinical course and treatment are reviewed. In addition, the similarities and differences with respect to the other idiopathic interstitial eosinophilic pneumopathies are described.

Validity of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for chronic alcohol abuse: a study in patients with alcohol dependence and liver disorders of non-alcoholic and alcoholic origin.

AIM: To test the clinical performance of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for alcoholism with a special focus on patients suffering from liver diseases. DESIGN: Well-characterized collectives of alcohol-dependent patients with current consumption (ALC patients, n = 101), and relevant control groups (115 social drinkers, 46 patients with unspecifically increased gamma-GT, 51 hepatitis patients and 20/31 patients with non-alcohol/alcohol-dependent liver cirrhosis) were included into the study. The Positive Alcohol Use Disorders Test (AUDIT) score, International Classification of Diseases version 10 (ICD-10)/Diagnostic and Statistical Manual version IV (DSM-IV) criteria and blood drawn within 4 days of last drinking were inclusion criteria for subjects with regular heavy drinking. %CDT was determined using an automated assay which recently had been completely modified. FINDINGS: Median AUDIT scores of patients without/with regular heavy drinking were 1-3/27. The following medians/95th percentiles were obtained for %CDT: social drinkers 2.2/3.0, patients with unspecifically increased gamma-GT 2.1/3.0, hepatitis 2.0/4.4, non-alcohol-dependent liver cirrhosis 2.4/4.8, alcohol-dependent liver cirrhosis 3.0/5.9, ALC patients 3.9/14.9. Differences between patients without and with alcohol abuse were highly significant (P < 0.001). No differences in CDT values were found between males and females. There was no correlation between %CDT values, gamma-GT, MCV and the amount of alcohol consumed in ALC patients; 3.0%CDT (95th percentile social drinkers) is proposed as cut-off for the test used (Tina-quant %CDT 2nd-generation). At this cut-off, the sensitivity for ALC patients was 73.3%, whereas gamma-GT/MCV had a sensitivity of 71.3%/64.4%. Multivariate analysis performed at 95% specificity resulted in an improvement of the sensitivity by combining %CDT with gamma-GT (83.2%). A further enhancement of the sensitivity to 88.1% was obtained by combination of %CDT, gamma-GT and MCV. The diagnostic specificity of %CDT calculated at the cut-off of 3% was 93.5% in patients with unspecifically increased gamma-GT, 88.2% in hepatitis patients and 70.0% in patients with non-alcohol-dependent liver cirrhosis. %CDT was more specific in these patient collectives than MCV, and especially more than gamma-GT (specificity in hepatitis 52.9%, and 35.0% in non-alcohol-dependent liver cirrhosis). CONCLUSION: %CDT is of high diagnostic value to support diagnosis of alcohol-use disorders. The specificity of this marker in patient groups with liver disorders is superior to the biomarkers gamma-GT and MCV.

Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease.

BACKGROUND AND AIMS: Recent data suggest identification of causal genetic variants for inflammatory bowel disease in the DLG5 gene and in the organic cation transporter (OCTN) cluster, both situated in previously described linkage regions. PATIENTS AND METHODS: The polymorphisms in DLG5 (113 G-->A, 4136 C-->A, and DLG5_e26), SLC22A4 (1672 C-->T), and SLC22A5 (-207 G-->C) were assessed in 625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis (UC), and 1012 healthy controls. Association with disease susceptibility, clinical phenotypes, and possible genetic interactions of these polymorphisms with disease associated CARD15/NOD2 mutations was analysed. RESULTS: No significant association of DLG5 polymorphisms with CD or UC was observed. Homozygosity for the OCTN-TC haplotype was associated with an increased CD risk (OR = 1.65), which was even greater in the presence of CARD15 mutations. Genotype-phenotype analysis revealed that this association was particularly strong in patients with colonic disease. The TC haplotype was associated with non-fistulising non-fibrostenotic disease, an earlier age of disease onset, and reduced need for surgery. CONCLUSION: Our observations argue against a role of DLG5 polymorphisms in the susceptibility for inflammatory bowel disease, whereas the OCTN polymorphisms are associated with CD. However, due to the comparable weak association observed herein, extended linkage disequilibrium analyses of these variants with the IBD5 haplotype tagged single nucleotide polymorphims might be advisable before definitive conclusions about their causative role in CD can be drawn.

Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically defined by familial clustering of colorectal cancer and other associated tumours. METHODS: By thorough molecular and clinical evaluation of 41 families, two different groups were characterised: group 1, 25 families with truncating mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam positive families without mutations in these genes and without microsatellite instability in their corresponding tumours. RESULTS: Significant clinical differences between these two groups were found. Firstly, earlier age of onset for all colorectal cancers (median 41 v 55 years; p < 0.001) and all tumours (median 43 v 56 years; p = 0.022) was observed, comparing groups 1 and 2. Secondly, 68% of the index colorectal cancers were localised proximally of the splenic flexure in group 1 compared with 14% in group 2 (p < 0.010). Thirdly, more synchronous and metachronous colorectal (p = 0.017) and extracolorectal tumours (p < 0.001) were found in group 1. Fourthly, a higher colorectal adenoma/carcinoma ratio (p = 0.030) and a tendency towards more synchronous or metachronous adenomas in group 2 (p = 0.084) was observed, indicating a slower progression of adenomas to carcinomas. As three mutation negative tumours revealed chromosomal instability after comparative genomic hybridisation, these tumours may be caused by one or more highly penetrant disease alleles from the chromosomal instability pathway. CONCLUSION: These data show that HNPCC includes at least two entities with clinical and molecular differences. This will have implications for surveillance programmes and for cancer research.

Detection of occult high graded microsatellite instabilities in MMR gene mutation negative HNPCC tumors by addition of complementary marker analysis.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant tumor syndrome predisposing to predominantly colorectal and endometrial cancer. In 90% of the cases, molecular analyses reveal microsatellite instabilities due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2, among these tumors. PATIENTS AND METHODS: Tumors from 40 HNPCC index patients (31 Amsterdam positive, 9 Bethesda positive; 21 females, 19 males; mean age 48.0 +/- 13.2 years) were examined. In contrast to the classical constellation, their tumors revealed only a microsatellite stable (MSS, n=31)--or low instable (MSI-L, n=9)--tumor phenotype following the international reference panel of 5 microsatellites. No MLH1 and MSH2 mutations were detectable. Complementary microsatellites (BAT40, D10S197, D13S153, D18S58, MYCL1) were investigated by PCR and fragment analysis to find other instabilities which might hint to the MIN-pathway of the tumors. RESULTS: Due to ten microsatellites in total tumors were now reclassified in 4 MSI-H (10%), 24 MSI-L (60%) and 12 in MSS (30%) phenotypes. The mean age of onset for CRCs was the lowest in the MSI-H group with 45.7 +/- 9.6 years (vs. 48.7 +/- 14.3 and 49.0 +/- 12.9 years in MSI-L and MSS group). MSI-H-and MSI-L tumors were often localized in the proximal colon (50 and 52%), whereas MSS tumors were preferentially localized in the distal colon (77%). - CONCLUSION: Complementary microsatellites help to subdive "non-classical" HNPCC in subgroups with different clinical appearance. It allows to detect occult MSI-H tumors with up to 10% and to confirm MSS tumors who seem to have a similar biological behaviour like sporadic CRC. Maybe that this genetic reclassification influence the decision of whether to offer patients chemotherapy or not, since it is known that patients with instable tumors do not benefit from chemotherapy as well as patients with microsatellite stable tumors.

[Aerobilia as an initial sign of a cholecystoduodenal fistula--a case report]. / Patientin mit langjähriger Cholezystolithiasis. Woran denken Sie bei Aerobilie?

An 82 year old female patient has the following medical history: repeated chemotherapy and radiation therapy for non-Hodgkin's lymphoma, a radiation-induced osteoblastic osteosarcoma and a longstanding cholecystolithiasis with sclero-atrophic cholecystitis. She appeared at the practice and complained about a dull food-dependent mesogastric and epigastric pain as well as a discrete scleral jaundice. Sonography and CT showed air inclusions in the bile ducts. Subsequently, a cholecystoduodenal fistula was found intraoperatively. The cause could be the long-existing cholecystolithiasis.

Ultrasound in emergency patients: better detection of free intraabdominal fluids by the use of tissue harmonic imaging.

BACKGROUND: Ultrasound examination is one of the main investigative procedures in emergency patients who are hospitalized due to abdominal pain. Detectable free fluid collections are important hints to the definite, sometimes life-threatening diagnosis, but their detection in cases of only small amounts is difficult to perform by conventional sonography. PATIENTS AND METHODS: We report about 25 cases of patients who suffered from acute abdominal pain and who were presented as emergency patients to our department of ultrasound. First, the examination was performed by conventional sonography (3.4 MHz). Only with the additional tissue harmonic imaging (THI, 2.3 MHz, pulse inversion) thin borders of free fluids around the liver or other abdominal organs (gallbladder, spleen, pancreas, bowel) could be detected leading to other important diagnostic or therapeutic steps. In this way, the diagnosis of pancreatitis, cholezystitis, peritonitis, peritoneal carcinosis, ascites (liver cirrhosis, serositis, postoperative status after laparotomy), bleeding or paralytic ileus could be elucidated. CONCLUSION: THI sonography improves the detection of small amounts of free abdominal fluid collections. Therefore, this technique is helpful in the diagnostic procedure of emergency patients.

Extended microsatellite analysis in microsatellite stable, MSH2 and MLH1 mutation-negative HNPCC patients: genetic reclassification and correlation with clinical features.

BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder predisposing to predominantly colorectal cancer (CRC) and endometrial cancer frequently due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2 and also MSH6 in families seen to demonstrate an excess of endometrial cancer. As a consequence, tumors in HNPCC reveal alterations in the length of simple repetitive genomic sequences like poly-A, poly-T, CA or GT repeats (microsatellites) in at least 90% of the cases. AIM OF THE STUDY: The study cohort consisted of 25 HNPCC index patients (19 Amsterdam positive, 6 Bethesda positive) who revealed a microsatellite stable (MSS)--or low instable (MSI-L)--tumor phenotype with negative mutation analysis for the MMR genes MLH1 and MSH2. An extended marker panel (BAT40, D10S197, D13S153, D18S58, MYCL1) was analyzed for the tumors of these patients with regard to three aspects. First, to reconfirm the MSI-L phenotype found by the standard panel; second, to find minor MSIs which might point towards an MSH6 mutation, and third, to reconfirm the MSS status of hereditary tumors. The reconfirmation of the MSS status of tumors not caused by mutations in the MMR genes should allow one to define another entity of hereditary CRC. Their clinical features were compared with those of 150 patients with sporadic CRCs. RESULTS: In this way, 17 MSS and 8 MSI-L tumors were reclassified as 5 MSS, 18 MSI-L and even 2 MSI-H (high instability) tumors, the last being seen to demonstrate at least 4 instable markers out of 10. Among all family members, 87 malignancies were documented. The mean age of onset for CRCs was the lowest in the MSI-H-phenotyped patients with 40.5 +/- 4.9 years (vs. 47.0 +/- 14.6 and 49.8 +/- 11.9 years in MSI-L- and MSS-phenotyped patients, respectively). The percentage of CRC was the highest in families with MSS-phenotyped tumors (88%), followed by MSI-L-phenotyped (78%) and then by MSI-H-phenotyped (67%) tumors. MSS tumors were preferentially localized in the distal colon supposing a similar biologic behavior like sporadic CRC. MSH6 mutation analysis for the MSI-L and MSI-H patients revealed one truncating mutation for a patient initially with an MSS tumor, which was reclassified as MSI-L by analyzing the extended marker panel. CONCLUSION: Extended microsatellite analysis serves to evaluate the sensitivity of the reference panel for HNPCC detection and permits phenotype confirmation or upgrading. Additionally, it confirms the MSS status of hereditary CRCs not caused by the common mutations in the MMR genes and provides hints to another entity of hereditary CRC.