Structural Changes Associated with Progression of Motor Deficits in Spinocerebellar Ataxia 17

Spinocerebellar ataxia (SCA17) is a rare genetic disorder characterized by a variety of neuropsychiatric symptoms. Recently, using magnetic resonance imaging (MRI) voxel-based morphometry (VBM), several specific functional–structural correlations comprising differential degeneration related to motor and psychiatric symptoms were reported in patients with SCA17. To investigate gray matter volume (GMV) changes over time and its association to clinical neuropsychiatric symptomatology, nine SCA17 mutation carriers and nine matched healthy individuals underwent a detailed neuropsychiatric clinical examination and a high-resolution T1-weighted volume MRI scan, both at baseline and follow-up after 18 months. Follow-up images revealed a progressive GMV reduction in specific degeneration patterns. In contrast to healthy controls, SCA17 patients showed a greater atrophy not only in cerebellar regions but also in cortical structures such as the limbic system (parahippocampus, cingulate) and parietal precuneus. Clinically, progression of motor symptoms was more pronounced than that of psychiatric symptoms. Correlation with the clinical motor scores revealed a progressive reduction of GMV in cerebellar and cerebral motor networks, whereas correlation with psychiatric scores displayed a more widespread GMV impairment in frontal, limbic, parietal, and also cerebellar structures. Interestingly, changes in global functioning were correlated with bilateral atrophy within the para-/hippocampus. While there was a good temporal association between worsening of motor symptoms and progression in cerebral and cortical neurodegeneration, the progression in psychiatric related neurodegeneration seemed to be more widespread and complex, showing progressive atrophy that preceded the further development of clinical psychiatric symptoms.     

Multiparameter immunofluorescence on paraffin-embedded tissue sections.

Immunohistochemical techniques have gained increasing importance in diagnostics and research. While formalin-fixed, paraffin-embedded human tissue retains excellent morphology, the detection of antigens by immunofluorescence in its sections and especially the demonstration of multiple simultaneous antibodies have limitations. Double immunofluorescence labeling of routinely processed paraffin sections has been described previously. The signal intensity observed after triple labeling has been reported to be significantly inferior to that obtained by application of double fluorochromes. The authors show multicolor labeling of three and four primary antibodies in routinely processed paraffin-embedded tissue sections using a standardized immunofluorescence technique. In addition, procedures to reduce background staining and to avoid nonspecific double staining are described.     

Simultaneous detection of HER2/neu gene amplification and protein overexpression in paraffin-embedded breast cancer

The determination of HER2/neu status in breast carcinomas has become essential for the selection of breast cancer patients for Herceptin therapy. Herceptin treatment is used in patients with metastatic breast carcinoma with HER2/neu protein overexpression detected by immunohistochemistry (IHC) or gene amplification analysed by fluorescence in situ hybridization (FISH). A multiparametric fluorescent approach based on the simultaneous detection of HER2/neu gene amplification and protein expression was established to increase the accuracy, and to improve the reproducibility, of HER2/neu diagnostics. Based on four paraffin-embedded breast cancer cell lines, a combined fluorescent immunostaining (FIHC) and FISH method was developed by using the PathVysion HER2 DNA Probe Kit (VYSIS) and the polyclonal antibody from the HercepTest (DAKO). Diagnostic applicability was documented on 215 formalin-fixed primary breast carcinomas. Criteria for immunofluorescence quantification were chosen by analogy with the FDA-approved HercepTest scoring, ranging from 0 to 3+. There was 97.7% concordance between conventional IHC and fluorescence IHC. The FISH data resulting from the multiparametric approach did not differ from conventional FISH. Breast carcinomas with HER2/neu protein overexpression and simultaneous gene amplification were detected with 100% sensitivity. In addition, five of the 215 cases (2.3%) had HER2/neu gene amplification without protein overexpression. The main advantage of this novel approach is that polysomy, aneuploidy, gene amplification, and protein content can be analysed simultaneously in the same cell.     

Endovascular repair of complex aortic aneurysms

Since the first published report of a fenestrated endovascular aneurysm repair, we have seen an expansion in the range of custom-made devices used to manage complex aortic aneurysms. Fenestrated devices, branched devices, and chimneys are now frequently used in many centers to repair these aneurysms. Similar to standard endovascular aneurysm repair, the advantages of less operative blood loss, decreased hospital stay, and reduced risk of morbidity and mortality hold true for endovascular repair of complex aneurysms as well. This is contrasted by the requirement for long-term surveillance and increased incidence of secondary interventions.     

Radical operations for carcinoma of the gallbladder: Present status in Germany

Despite the overall poor prognosis of gallbladder carcinoma, it appears that, in resectable lesions, an aggressive surgical approach promises improvement in survival rates. Radical treatment of gallbladder carcinoma is based on a detailed knowledge of the lymphatic, venous, direct, and intraductal modes of spread of gallbladder carcinoma. Customized therapy of gallbladder carcinoma takes staging into consideration: if one is dealing with gallbladder carcinoma with macroscopic liver infiltration (T3 or T4), or with a pre- or intraoperatively diagnosed gallbladder carcinoma with an unknown depth of infiltration, an en bloc resection of the gallbladder with adjacent liver segments IVb and V, perhaps including VI, as well as a dissection of the hepatoduodenal ligament should be performed. If the carcinoma is missed intraoperatively at the time of cholecystectomy for other indications, in the presence of a T2 gallbladder carcinoma in proximity to the liver bed, reoperation with dissection of the hepatoduodenal ligament and resection of liver segments IVb and V should be performed. In the presence of T1 gallbladder carcinoma, simple cholecystectomy is adequate.This concept is based on our experience with 113 patients with gallbladder carcinoma who underwent treatment in our department from January, 1970 to June, 1989. Sixty-seven percent of the gallbladder carcinomas were resected, 30% for cure and 37% palliatively. In 33%, the operation was limited to an exploratory laparotomy or a palliative operation, or no operation was performed. Of the curatively resected carcinomas (n=34), 7 were Stage I, 7 Stage II, 9 Stage III, and 11 Stage IV.The average follow-up or survival time following curative resection at first operation (n=21) was 48.1 months; survival in patients who underwent curative resection at reoperation, in the presence of distant metastases, if there was tumor spillage, and in the presence of synchronous tumor was 14.0 months; survival following palliative resection was 5.8 months, and after exploratory laparotomy, palliative operation, or no operation was 3.6 months.Compared to palliative resection, customized therapy of gallbladder carcinoma for cure at the time of initial operation leads to a significant improvement in prognosis.

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Resumen A pesar del pobre pronóstico general del carcinoma de la vesícula biliar, es aparente que en las lesiones resecables un aproche quirúrgico radical promete mejores tasas de sobrevida. El tratamiento radical del carcinoma de la vesícula biliar se fundamenta en un conocimiento detallado de las modalidades de extensión linfática, venosa, directa, e intraductal del carcinoma de la vesícula biliar. La terapia es individualizada de acuerdo al estadio: si se trata de un carcinoma con infiltración macroscópica del hígado (T3 o T4), o de un carcinoma diagnosticado pre- o intraoperatoriamente con grado de infiltración no determinado, se debe proceder con una resección en bloque de la vesícula biliar y los segmentos hepáticos adyacentes IVb, y V, tal vez incluyendo VI, junto con disección del ligamento hepatoduodenal. Si el carcinoma no es detectado intraoperatoriamente en el momento de una colecistectomía realizada por otra indicación, en presencia de un carcinoma T2 en proximidad al lecho hepático, se debe emprender la reoperación con disección del ligamento hepatoduodenal y resección de los segmentos hepáticos IVb y V. En presencia de un carcinoma T1, la simple colecistectomía constituye tratamiento adecuado.Este concepto se fundamenta en nuestra experiencia con 113 pacientes con carcinoma de la vesícula biliar que fueron sometidos a tratamiento en nuestro departamento entre enero de 1970 y junio de 1989. Sesenta y siete por ciento de los carcinomas fueron resecados, 30% en forma curativa y en 37% en forma paliativa. En 33% la operación estuvo limitada a una laparotomía exploratoria o una intervención paliativa, o no se realizó operación. De los carcinomas resecados en forma curativa (n= 34), 7 fueron Estado I, 7 Estado II, 9 Estado III, y 11 Estado IV.El seguimiento promedio o tiempo de sobrevida después de una resección curativa en la primera intervención (n=21) fue 48.1 meses; después de una resección curativa en reoperación, en presencia de metástasis distantes, o si hubo desgarre del tumor o en presencia de tumor sincrónico, fue 14.0 meses; después de resección paliativa 5.8 meses y después de laparotomía exploratoria, operación paliativa o no operación, 3.6 meses.En comparación con la resección paliativa, la terapia indiviudalizada del carcinoma de la vesícula biliar con intención de curación realizada, en el momento de la primera operación, da lugar a una mejoría significativa del prónostico.

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Résumé Bien que le pronostic de cancer de la vésicule biliaire soit généralement mauvais, il semble que pour les lésions qu'on peut réséquer, l'approche chirurgicale agressive permette d'améliorer les taux de survie. Le traitement radical de la vésicule biliaire repose sur la connaissance parfaite de la dissémination à distance à partir de la vésicule dans les voies lymphatiques, veineuses, directes et biliaires. Le traitement courant du cancer de la vésicule biliaire tient compte du stade; si on traite un cancer de la vésicule biliaire avec une infiltration macroscopique du foie (T3 ou T4), ou un cancer de la vésicule biliaire diagnostiqué avant ou pendant l'intervention et dont on ne connaît pas l'étendue de l'envahissement, on doit faire une résection en bloc de la vésicule biliaire et des segments adjacents du foie IVb et V, peut-être même VI, ainsi que du ligament hépatoduodénal (petit épiploon). Si le cancer est passé inaperçu lors d'une cholécystectomie pratiquée pour d'autres diagnostics, devant un cancer T2 de la vésicule biliaire près du lit du foie, on doit faire une nouvelle intervention avec lymphadénectomie du ligament hépatoduodénal et une résection des segments IVb et V du foie. Pour un cancer T1 de la vésicule biliaire, la simple cholécystectomie suffit.Cette théorie se fonde sur notre expérience de 113 patients ayant un cancer de la vésicule biliaire et ayant eu un traitement dans notre service de janvier 1970 à juin 1989. Dans 67% des cas de cancers de la vésicule biliaire, on a fait une résection, à visée curative chez 30% des patients et à visée palliative chez 37%, Chez 33% des patients, l'intervention a été limitée à la laparotomie exploratrice ou à une intervention palliative, ou bien aucune intervention n'a été pratiquée. Pour les résections à visée curative (n=34), 7 cancers étaient de Stade I, 7 de Stade II, 9 de Stade III, et 11 de Stade IV.Le temps moyen de survie après résection à visée curative en première intervention (n=21) était de 48.1 mois; après résection à visée curative en seconde intention, avec métastases à distance, s'il y a eu effraction de la capsule tumorale et avec tumeur synchrone, 14.0 mois; après résection à visée palliative, 5.8 months et après laparotomie exploratrice, intervention à visée palliative ou pas d'opération, 3.6 mois.Comparé à la résection à visée palliative, le traitement courant du cancer de la vésicule biliaire au moment de la première intervention améliore le pronostic de façon significative.

     

Eosinophil‐rich trichoblastic carcinoma with aggressive clinical course in a young man

We present the case of a 35‐year‐old man who developed a follicular differentiated cutaneous carcinoma with an eosinophil‐rich infiltrate and an aggressive clinical behavior. After an in‐depth histopathological investigation the diagnosis of trichoblastic carcinoma was made. Over the course of the disease the patient developed a cutaneous in‐transit metastasis as well as an axillary lymph node metastasis 18 months after the excision of the primary tumor on his back. Based on a literature review we discuss the different concepts behind the term “trichoblastic carcinoma” and we summarize the clinical and histological details of previously reported cases. Furthermore, we focus on the phenomenon of tumor‐associated eosinophilia.