Effects of a sensory branch to the posterior external ear canal: coughing, pain, Ramsay Hunt's syndrome and Hitselberger's sign.

BACKGROUND: A distinct nerve innervating the external auditory canal can often be identified in close relation to the facial nerve when gradually thinning the posterior canal wall. This nerve has been attributed to coughing during cerumen removal, neuralgic pain, Hitselberger's sign and vesicular eruptions described in Ramsay Hunt's syndrome. This study aimed to demonstrate the origin and clinical impact of this nerve. METHODS AND RESULTS: In patients with intractable otalgia or severe coughing whilst inserting a hearing aid, who responded temporarily to local anaesthesia, the symptoms could be resolved by sectioning a sensory branch to the posterior canal. In a temporal bone specimen, it was revealed that this nerve is predominantly a continuation of Arnold's nerve, also receiving fibres from the glossopharyngeal nerve and facial nerve. Histologically, the communicating branch from the facial nerve was confirmed. CONCLUSION: Surgeons should be aware of the posterior auricular sensory branch and its clinical implications.

Displacement of malignant cells into the portal triad of the liver results in reduced liver perfusion, mimicking segmental Fatty liver.

Liver steatosis is often observed in different clinical situations. Oncological patients undergoing systemic therapy often develop liver steatosis, which can be diagnosed with normal routine scans such as CT and ultrasound. In this case report, we show that an isolated infiltration of the portal triad with tumor cells could mimic a fatty-like infiltration of the liver. Radiologists and clinicians should be aware of this pitfall and should perform a biopsy in cases of doubt.

Comparison of histopathological findings with duplex sonography of the temporal arteries in suspected giant cell arteritis.

INTRODUCTION: In clinical practice the temporal artery biopsy (TAB) in suspected giant cell arteritis (GCA) is still believed to be the "gold standard". The purpose of this study was to compare the histopathological findings of the TAB with duplex sonography of the temporal artery. PATIENTS AND METHODS: In our retrospective study we analysed 85 consecutive patients (52 female, mean age 71.5, range 55 - 91 years; 33 male, mean age 71.6, range 44 - 91 years) with suspected GCA who underwent TAB in our clinic between January 1999 - February 2011. All patients received a preoperative duplex sonography, 57 patients including description of the temporal arteries. RESULTS: 38 of 85 (44.7 %) of the artery biopsies were proven positive for GCA by histopathology. Interpretation of the duplex sonography was congruent of histopathological interpretation of the biopsy in 39 patients (68.4 %) and incongruent in 18 patients (31.6 %). Sensitivity of duplex-sonography was 44.4 %, specificity 90 %, positive predictive value 80 %. DISCUSSION: Duplex sonography is a non-invasive and very helpful diagnostic tool to guide the clinician in cases of suspected GCA but needs considerable skills. It shows a good specificity and relatively high positive predictive value as there are only few false positive results. A negative report however does not rule out GCA, so that in our opinion the TAB - at least in those cases - should still be performed.

[Metastazation into the seminal vesicles due to primary goblet cell carcinoid of the vermiform appendix. An unusual diagnostic procedure of a seminal vesicle tumor]. / Samenblasenmetastase bei primärem Becherzellkarzinoid der Appendix vermiformis. Ein aussergewöhnlicher Abklärungsgang eines Samenblasentumors.

We report on a remarkable diagnostic work up of suspect rectal palpation results in a 54-year-old patient. According to a transrectal ultrasound-guided punch biopsy the patient was suspected of having a carcinoma of the seminal vesicles and an aggressive operational approach was considered. After a median laparotomy a generalized peritoneal carcinomatosis was found. A goblet cell carcinoid of the vermiform appendix was identified as the primary tumor. This case report deals with metastazation of a primary goblet cell carcinoma into the seminal vesicles on both sides as an extremely rare reason for suspicious rectal palpation results. The tumor valency, diagnostic work up, therapy and further differential diagnoses are described.

Exercise capacity in athletes with mouthguards.

The objective of this study was to determine the effect of wearing a mouthguard on maximal exercise capacity and cardiopulmonary parameters at peak workload, and to assess the athletes' attitudes toward wearing a mouthguard. Thirteen volunteer male athletes (18 to 27 years old) were interviewed before and after delivery of a custom-made laminated mouthguard. A visual analogue scale (VAS, 0 - 100 mm) was used for judgment of interference with breathing, speaking, concentration and athletic performance. In addition, the athletes were subjected to a cardiorespiratory examination on a cycle ergometer with and without mouthguards. Subjectively, the athletes rated the mean interference with performance to be 37 mm VAS at the beginning of the study. Mean scores of impairment decreased to 23 mm VAS (p = 0.081) after wearing the mouthguard for four weeks, and further improved to 12 mm VAS (p < 0.001) after the test on the cycle ergometer. Objectively, the maximum workload during spiroergometry was even slightly elevated during exercise with the mouthguard (330.2 W) compared to exercise without the mouthguard (314.5 W). Peak minute ventilation and oxygen uptake were not different during exercise with and without the mouthguard. The present study demonstrated that a custom-made mouthguard does not significantly affect or reduce maximum exercise performance of athletes.

[Inflammatory myofibroblastic tumour (so-called pseudotumour) of the hepatobiliary system]. / Entzündlicher myofibroblastischer Tumor (sog. inflammatorischer Pseudotumor) des hepatobiliären Systems.

The purpose of this report is to describe the ultrasonographic features of hepatic inflammatory myofibroblastic tumour (IMT). This tumour presented as an area of periportal soft-tissue infiltration. Because periportal infiltration is a common feature in both IMT and other malignant tumours of the hepatic portal, histological examination should be considered before final diagnosis and treatment.

[Acute fatty liver in pregnancy: clinical and histopathological course. Case report]. / Akute Schwangerschaftsfettleber: Klinischer und histopathologischer Verlauf. Kasuistik

Acute fatty liver of pregnancy is a rare disease which may be letal if diagnosis is missed. The pathogenesis is not completely clear, but there is some evidence that some cases have been associated with a genetic deficiency of fatty acid beta-oxidation. Other predisposing factors include primiparity, multiple pregnancy, male fetal sex and pre-eclampsia. Clinical presentation and laboratory findings are often unspecific. Increasing serum aminotransferases are characteristic in the early stage of the disease. Liver biopsy establishes the diagnosis and typically shows microvesicular, centrilobular fatty changes of hepatocytes. Differential diagnosis includes the HELLP-Syndrome, cholestasis of pregnancy, pre-eclampsia and viral or drug induced hepatitis. Without adequate treatment liver failure with coagulopathy and encephalopathy may develop. Two cases of acute fatty liver in pregnancy in an early stage are presented. Clinical and histopathological findings as well as diagnostic and therapeutic procedures are discussed.

Relationship between APC genotype, polyp distribution, and oral sulindac treatment in the colon and rectum of patients with familial adenomatous polyposis.

PURPOSE: Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps. Molecular studies have revealed that germline mutations in the APC gene are the underlying cause of the disease. The nonsteroidal anti-inflammatory agent sulindac has been shown to reduce the number of colorectal adenomas. Most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of the APC mutation affects the efficacy of sulindac. METHODS: This study investigated whether there were regional differences in the effect of sulindac on the colon and whether response to sulindac was dependent on the site of mutation in the APC gene. In an open prospective study 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for four months followed by a washout phase of six months. Ten of the patients had an intact colon and seven had rectal stumps only. The number, size, and the degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment and end of the study. RESULTS: Overall, a statistically significant decrease in the number of adenomas was observed (120 +/- 112 to 28 +/- 64, P = 0.007). After cessation of sulindac treatment the number of adenomas increased to 48 +/- 44.5, but remained significantly lower than the values observed at baseline. In the ten patients with intact colons, adenomas decreased by sevenfold in the proximal colon (103 +/- 73 to 15.1 +/- 47.4, P = 0.011) and twofold in the distal colon (80 +/- 52 to 29.6 +/- 37.2, P = 0.005). The size of adenomas and the grade of dysplasia also decreased. No correlation could be seen between the APC mutation site and the response to treatment. CONCLUSION: These data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon.

Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade.

The number of genes suggested to play a role in cancer biology is rapidly increasing. To be able to test a large number of molecular parameters in sufficiently large series of primary tumours, a tissue microarray (TMA) approach has been developed where samples from up to 1000 tumours can be simultaneously analysed on one glass slide. Because of the small size of the individual arrayed tissue samples (diameter 0.6 mm), the question arises of whether these specimens are representative of their donor tumours. To investigate how representative are the results obtained on TMAs, a set of 2317 bladder tumours that had been previously analysed for histological grade and Ki67 labelling index (LI) was used to construct four replica TMAs from different areas of each tumour. Clinical follow-up information was available from 1092 patients. The histological grade and the Ki67 LI were determined for every arrayed tumour sample (4x2317 analyses each). Despite discrepancies in individual cases, the grade and Ki67 information obtained on minute arrayed samples were highly similar to the data obtained on large sections (p<0.0001). Most importantly, every individual association between grade or Ki67 LI and tumour stage or prognosis (recurrence, progression, tumour-specific survival) that was observed in large section analysis could be fully reproduced on all four replica TMAs. These results show that intra-tumour heterogeneity does not significantly affect the ability to detect clinico-pathological correlations on TMAs, probably because of the large number of tumours that can be included in TMA studies. TMAs are a powerful tool for rapid identification of the biological or clinical significance of molecular alterations in bladder cancer and other tumour types.

High-throughput tissue microarray analysis of 3p25 (RAF1) and 8p12 (FGFR1) copy number alterations in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the chromosomal regions 3p25 and 8p11-p12 are recurrently amplified in bladder cancer. To investigate the prevalence of DNA copy number alterations in these chromosomal regions and study their clinical significance, we used probes for the RAF1 (3p25) and FGFR1 (8p12) genes for fluorescence in situ hybridization. A tissue microarray containing 2317 tumors was analyzed. The analysis revealed RAF1 amplification in 4.0% and FGFR1 amplification in 3.4% of interpretable tumors. In addition, deletions were found at the 3p25 locus in 2.2% and at the 8p11-12 locus in 9.9% of interpretable tumors. Both amplifications and deletions of RAF1 and FGFR1 were significantly associated with high tumor grade (P < 0.0001), advanced stage (P < 0.0001), and poor survival (P < 0.05) if tumors of all of the stages where analyzed together. RAF1 amplifications were associated with subsequent tumor progression in pT1 carcinomas (P < 0.05). The marked differences in the frequency of all of the analyzed changes between pTa grade 1/grade 2 and pT1-4 carcinomas support the concept of these tumor groups representing different tumor entities.

High-throughput tissue microarray analysis of cyclin E gene amplification and overexpression in urinary bladder cancer.

Studies by comparative genomic hybridization revealed that the 19q13 chromosomal region is frequently amplified in bladder cancer. The cyclin E gene (CCNE), coding for a regulatory subunit of cyclin-dependent kinase 2, has been mapped to 19q13. To investigate the role of cyclin E alterations in bladder cancer, a tissue microarray of 2,317 specimens from 1,842 bladder cancer patients was constructed and analyzed for CCNE amplification by fluorescence in situ hybridization and for cyclin-E protein overexpression by immunohistochemistry. Fluorescence in situ hybridization analysis showed amplification in only 30 of the 1,561 evaluable tumors (1.9%). Amplification was significantly associated with stage and grade (P: < 0.0005 each). Immunohistochemically detectable cyclin E expression was strong in 233 (12.4%), weak in 354 (18.9%), and negative in 1, 286 of the 1,873 interpretable tumors. The majority (62.1%) of CCNE-amplified tumors were strongly immunohistochemistry-positive (P: < 0.0001). The frequency of protein expression increased from stage pTa (22.2%) to pT1 (45.5%; P: < 0.0001) but then decreased for stage pT2-4 (29.4%; P: < 0.0001 for pT1 versus pT2-4). Low cyclin E expression was associated with poor overall survival in all patients (P: < 0.0001), but had no prognostic impact independent of stage. It is concluded that cyclin E overexpression is characteristic to a subset of bladder carcinomas, especially at the stage of early invasion. This analysis of the prognostic impact of CCNE gene amplification and protein expression in >1,500 arrayed bladder cancers was accomplished in a period of 2 weeks, illustrating how the tissue microarray technology remarkably facilitates the evaluation of the clinical relevance of molecular alterations in cancer.

Sebaceous carcinoma of the breast.

We report on a rare distinctive variant of infiltrating ductal carcinoma characterized by sebaceous differentiation of tumor cells. The neoplasm was identified in a lumpectomy specimen from a 45-year-old woman with extensive metastatic disease. In addition to conventional in situ and invasive ductal components, approximately half of the tumor cells exhibited a phenotype resembling tumors of the sebaceous skin appendage with coarsely vacuolated cytoplasm and peripherally displaced nuclei. The sebaceous moiety was also present in the distant metastatic deposits. There was no evidence of mucin production by tumor cells. Ultrastructurally, empty-appearing non-membrane bound vacuoles attested to the sebaceous cells' lipid content. The immunoprofile of the lesion included positivity for cytokeratin and epithelial membrane antigen. Vimentin, S100 protein and carcinoembryonic antigen were not expressed. Most tumor cell nuclei reacted with antibodies to oestrogen and progesterone receptors but failed to show overexpression of the HER2/neu protein. The MIB-1 labeling index averaged 16%. At variance with sebaceous breast carcinomas on record, the present case is notable for its prolonged clinical course.

[From Hashimoto thyroiditis to B-cell lymphoma of the thyroid gland]. / Von der Hashimoto-Thyreoiditis zum B-Zell-Lymphom der Schilddrüse.

Lymphoma of the thyroid gland is an uncommon condition occurring primarily in older women. Most patients have a short history of an enlarging thyroid or a neck mass causing tracheal compression. There is also a strong association between thyroid lymphoma and Hashimoto's thyroiditis. The diagnosis is established by biopsy. The conventional approach to treatment is combination of radiation therapy with multi-agent chemotherapy, while there is no significant role for extirpative surgery in the management of thyroid lymphoma. The prognosis of localised tumours (stage IE, Ann Arbor classification) is excellent. Extrathyroidal involvement (stage IIE-IVE) reduces the 5-year survival rate to about 70%, provided that current therapy regimens are respected. In this case report, the different stages of development from Hashimoto's thyroiditis to thyroid lymphoma are demonstrated by histology. In a review of the literature we discuss the diagnostic procedure and the current approach to treatment.

[Angiosarcoma of the kidney. Case report and review of the literature]. / Angiosarkom der Niere. Fallbeispiel und Literaturübersicht.

The primary renal angiosarcoma is a rarely seen highly malignant tumor. Making a diagnosis based on histology may prove difficult. Because of hematogenous formation of metastases and bad prognosis in most cases we recommend that the surgical intervention be followed by the well tolerated systemic chemotherapy with Doxorubicin and Ifosfamid.

[Liver changes in AIDS. Retrospective analysis of 227 autopsies of HIV-positive patients]. / Leberveränderungen bei AIDS. Retrospektive Analyse von 227 Sektionen HIV-positiver Patienten.

In a retrospective study of a 12-year period (1981-1992) liver histology was analyzed in 227 autopsied patients infected with the human immunodeficiency virus. Normal histology could only be documented in 29 patients (13%). In the majority of cases (56%) uncharacteristic changes were seen such as steatosis (34%), hemosiderosis (10%) or non-specific reactive hepatitis (7%). The finding of hepatic peliosis obtained in 4 patients was not associated with inflammatory liver changes, especially infections from Rochalimaea. Within a wide range of opportunistic infections recorded in 50 patients (22%), hepatitis caused by Cytomegalovirus (8%), Toxoplasma gondii (5%), Leishmania donovani (1%), Cryptococcus neoformans and Pneumocystis carinii (each 0.5%) was diagnosed. Among 16 cases (7%) of mycobacterial liver infections typical mycobacteria were found in two patients and atypical mycobacteria in 14 patients, respectively. In 23 patients (10%) chronic viral hepatitis, caused by HBV (7%) or HCV infections (3%), respectively, was observed. Hepatitis was typed as mild only in each 5 patients with HBV or HCV infection, whereas the remaining cases showed a transition towards cirrhosis. Two patients with HBV-associated cirrhosis developed hepatocellular carcinoma. The remaining 32 malignant liver tumors represented secondary neoplasms, including 13 cases of non-Hodgkin's lymphomas.

Diagnosis of MALT lymphoma by conjunctival biopsy: a case report.

BACKGROUND: Most extranodular lymphatic tissue is found in the intestinal mucosa. Together with similarly structured lymphatic tissue at other locations it has been named mucosa-associated lymphatic tissue (MALT). Malignant transformation of such tissue to lymphoma is well known. Although MALT lymphoma has been described in tissue physiologically void of MALT, lymphoma manifestation in the conjunctiva is rare. METHODS: We report a case of a 47-year-old woman who was referred to our clinic for symptomatic treatment and evaluation of severe symptoms of dry eyes. She was thought to suffer from Sjögren's syndrome because of xerophthalmia and xerostomia, as well as massive bilateral swelling of the parotid gland. Ophthalmological examination revealed marked hyperplasia of the conjunctiva, of which a biopsy was taken. RESULTS: Histological and immunohistochemical examination of the conjunctival biopsy, together with analysis of gene rearrangement by Southern blot, led to the diagnosis of low-grade B-cell lymphoma of the MALT. CONCLUSION: The differential diagnosis of keratoconjunctivitis sicca presenting with conjunctival swelling of unknown origin should include lymphoma, especially since Sjögren's syndrome may be associated with malignant disorders of the lymphatic system. A biopsy of suspicious conjunctival changes can clarify a multisystem disease by providing a tissue diagnosis.

Magnetic resonance-guided laparoscopic interstitial laser therapy of the liver.

BACKGROUND: There is a necessity for an imaging method during laparoscopy to get a three-dimensional access to the target. In this study we evaluated laparoscopic interstitial laser therapy of the liver under magnetic resonance imaging guidance. METHODS: Five domestic pigs underwent laparoscopy in an open-configuration magnetic resonance system. Under simultaneous real-time magnetic resonance imaging interstitial laser therapy was applied to the liver. Magnetic resonance images, macroscopic aspects of the lesions, and light microscopic findings were compared. RESULTS: The interventions could be safely performed. There was no image artifact caused by instruments or by the carbon dioxide. Dynamic gadolinium-enhanced imaging proved to significantly predict the macroscopic volume of the laser lesions. CONCLUSIONS: Magnetic resonance-guided laparoscopic interstitial laser therapy of the liver combines the advantages of minimal invasive surgery and magnetic resonance imaging. Further development should focus on laparoscopic instruments and temperature sensitive sequences.

[Disseminated mycobacteriosis with M. kansasii in a case of AIDS without HIV infection]. / Disseminierte Mykobakteriose mit M. kansasii bei einem Fall von Aids ohne HIV-Infektion.

M. kansasii is an environmental Mycobacterium that causes disease mainly in patients with local or systemic immunodeficiency. We present a case with disseminated M. kansasii infection which led to a severe febrile illness lasting for 9 months. The patient had a combined acquired immunodeficiency syndrome (AIDS) which included CD4+ and CD8+ T-lymphocytopenia, monocytopenia and a deficiency in the IgG subclasses 2 and 4. HIV testing was repeatedly negative. In the published literature only 4 of 10 similar patients (this patient included) survived a disseminated M. kansasii infection. Eleven years after the disseminated infection with M. kansasii a second opportunistic infection, disseminated mollusca contagiosa and hyperparathyroidism, developed, and 14 years later the immunologic abnormalities persist.

[Comparative effect of lansoprazole/amoxicillin with omeprazole/amoxicillin for the eradication of Helicobacter pylori in patients with duodenal ulcer]. / Wirkungsvergleich von Lansoprazol/Amoxicillin mit Omeprazol/Amoxicillin zur Eradikation von Helicobacter pylori bei Patienten mit Duodenalulkus.

Lansoprazole, a potent antisecretory drug, possesses on an equimolar basis a 4-fold higher in vitro anti-Helicobacter pylori activity than omeprazole. In a prospective randomized study we compared lansoprazole 30 mg b.i.d. and amoxicillin 1 g b.i.d. with omeprazole 40 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days followed by lansoprazole 30 mg q.d. or omeprazole 20 mg q.d. for 14 additional days in 50 H. pylori positive duodenal ulcer patients (14f, 36m, age 27-83 [mean 43] years). H. pylori infection was diagnosed by histology (3 antral biopsies and 2 from gastric body, H & E- and Giemsa stain), rapid urease test (CLO) and culture in 39 patients, or by histology and rapid urease test in 11 patients. Control endoscopy was performed 4-6 weeks after the end of treatment. For eradication, a negative result in all 3 diagnostic modalities was required. The eradication rate was 43% (9/21 patients) in both treatment groups. 8 patients were lost to follow-up. The ulcer healing rate was 100% in both groups. Nonsmokers had a significantly higher (p = 0.026) eradication rate than smokers. No relevant adverse effects of the therapy occurred. 24 patients with persistent H. pylori infection were subsequently treated with lansoprazole 60 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days. Eradication was achieved in 5/22 (23%) patients (3/14 smokers, 2/8 nonsmokers), while 2 patients were lost to follow-up. 17 patients with persistent H. pylori infection after the second treatment received quadruple therapy consisting of metronidazole 500 mg t.i.d., tetracycline 500 mg q.i.d. bismuth-subcitrate 120 mg q.i.d. and lansoprazole 30 mg for 10 days. H. pylori eradication was achieved in 12/15 patients (80%). In conclusion, lansoprazole plus amoxicillin was equal to omeprazole plus amoxicillin in the treatment of H. pylori infected duodenal ulcer patients. Patients with eradication failure after dual therapy were successfully treated by quadruple therapy. In contrast, high dose lansoprazole and amoxicillin therapy was effective in only 23% of patients with persistent infection after standard dual therapy.

Experimental cryosurgery of the liver under magnetic resonance guidance.

The feasibility and the advantages of magnetic resonance (MR)-guided interstitial cryosurgery of the liver in an 0.5 Tesla open MR system have been evaluated. Cryosurgery was performed using an Erbocryo PS system with a nonmagnetic cryoprobe of 6 mm diameter. The probe was inserted into the liver parenchyma under real-time MR control. Using continuous MR imaging two freezing cycles of 12 min each were applied. After conventional and dynamic gadolinium-enhanced MR imaging, the animals were sacrificed after 30 min, 3 hr, 24 hr, 7 days, and 21 days. Each lesion was analyzed using light microscopy. A total of seven cryolesions were made in five animals without any complications from cryosurgery. During real-time imaging, cryolesions appeared as a hemispherical growing signal loss with a mean volume of 16.4 cm3. Macroscopic volumes of the lesions showed a good correlation with dynamic enhanced MR images during follow-up, whereas real-time images usually showed an underestimation of the lesion volumes. Cryosurgery of the liver in an open-configuration MR system is a feasible and safe method. MR imaging allows the guidance and the follow-up of cryolesions of the liver with good accuracy.