[Secondary retroperitoneal fibrosis in a 39-year-old man after rectal cancer]. / Sekundäre retroperitoneale Fibrose nach Rektumkarzinom bei einem 39-jährigen Mann.

A 39-year-old man had been treated for rectal cancer 6 years ago by lower anterior resection of the rectum and perioperative radiochemotherapy. Since then follow-up had been unremarkable but now the patient presented with unspecific lower abdominal pain. The cause of the pain was identified as paraneoplastic retroperitoneal fibrosis secondary to metachronous pulmonary metastases of the rectal cancer.

Influence of two types of self-retaining retractors on multifidus muscle blood flow during dorsolateral thoracolumbar hemilaminectomy in dogs.

OBJECTIVES: To assess the influence of the use of Gelpi and Grevel retractors on multifidus muscle blood flow during hemilaminectomy, using a dorsolateral approach, for acute disc extrusion in dogs as measured by laser speckle contrast imaging (LSCI). METHODS: Blood flow in the multifidus muscles was measured intra-operatively using LSCI prior to insertion of the retractors, immediately after hemilaminectomy and removal of the retractors, and after 10 minutes of lavage of the surgical site. Plasma creatine kinase levels were measured preoperatively and 12-24 hours postoperatively. RESULTS: Muscular blood flow was significantly decreased following retraction and remained lower than initial values 10 minutes after lavage in all dogs. The decrease in blood flow was significantly greater with Gelpi retractors (n = 8) than with Grevel retractors (n = 10). No significant relation was found between the duration of retraction and postoperative changes in creatine kinase levels or blood flow. CLINICAL SIGNIFICANCE: Findings in this study demonstrate a drop in blood flow within the multifidus muscles using the dorsolateral approach regardless of retractor type used. Gelpi retractors seem to have greater influence on muscular blood flow than Grevel retractors. Further studies are warranted to confirm this second finding.

[Severe anemia and chronic alcohol abuse lacking signs of gastrointestinal bleeding in a 40-year-old]. / Ausgeprägte Anämie bei chronischem Alkoholabusus ohne gastrointestinale Blutungsstigmata bei einem 40-Jährigen.

We report about a 40 year old patient presenting a severe anemia caused by a folate deficiency combined with chronic alcohol abuse and probable liver cirrhosis. Besides pathophysiology and etiology of folate deficiency the correlation of malnutrition and liver cirrhosis (in particular caused by alcohol abuse) is discussed. As a conclusion for clinical practice the necessity of an extensive investigation for causes of an existing anemia, even in cases, which very much seem to be caused by an acute bleeding event, shall be demonstrated. Furthermore this report shows the importance of a consistent nutrition counseling of patients with liver cirrhosis.

[Cholestatic hepatitis in situs inversus abdominalis]. / Cholestatische Hepatitis bei Situs inversus abdominalis.

A 75 year old patient was admitted to hospital due to painless jaundice and fatigue. Patient's history was not remarkable for chronic viral hepatitis, autoimmune hepatitis, hereditary metabolic disorders or a hepatotoxic damage. Laboratory tests revealed significant elevation of the parameters of cholestasis and aminotransferase activity, a significantly elevated titer of both antinuclear (ANA) and antimitochondrial (AMA) antibodies. Abdominal ultrasound and computertomography showed no mechanic cholestasis nor tumorous process but a situs inversus abdominalis of the abdominal parenchymatous organs. Portal and periportal inflammation, consistent with autoimmune hepatitis, was diagnosed histologically after performing laparoscopic liver biopsy. Regarding the significantly elevated cholestatic parameters and the positive AMA-autoantibodies AIH-PBC overlap syndrome was highly probable so medical treatment including both ursodeoxycholic acid and immunosuppressive therapy with corticosteroids and azathioprine was started resulting in a continous downward tendency of liver enzymes and an improvement of the patient's clinical condition. Finding the correct diagnosis and therapy of autoimmune liver disease is not always easy and unproblematic. Regarding its sometimes fatal progression and good response towards medical treatment prompt diagnosis and institution of autoimmune hepatitis--alone or combined as PBC/AIH overlap syndrome--should not be deferred. Laparoscopic liver biopsy should be the method of choice in patients's with situs inversus abdominalis regading the variable anatomy.

Is there a difference between diabetic and non-diabetic ITAs? Histomorphological and immunohistochemical examinations of internal thoracic arteries.

BACKGROUND: The relative resistance to arteriosclerosis of the internal thoracic artery is clinically valid. The aim of this study was to evaluate the graduation of intima and media fibrosis in ITA parts and to determine the extent of atherosclerosis using immunohistochemical methods related to patients' risk factors. METHODS: 227 distal ITA segments from 144 male and 83 female patients were examined. Mean age was 66.7 +/- 9.03 years. HE and Elastica van Gieson staining was performed to detect intima-/mediafibrosis. POPULATION: insulin-dependent diabetes mellitus (idDM; n = 35), non-insulin-dependent diabetes mellitus (nidDM; n = 32), irradiation of the chest due to cancer (n = 27), control group with isolated hyperlipidemia, hypertension, peripheral vascular disease (n = 133). 12 ITA segments of each group were examined immunohistochemically using CD34, CD68, Tenascin, Collagen III, Collagen IV. RESULTS: Histomorphological examinations using HE and Elastica van Gieson stainings showed for idDM-ITAs no fibrosis in 57 %, slight fibrosis in 34 %, medium in 6 %, no severe, for nidDM-ITAs no fibrosis in 63 %, slight 31 %, medium 3 %, severe 3 %, for ITAs after irradiation: no fibrosis in 37 %, slight in 62 %, no medium or severe fibrosis. Compared to the control group there was no statistically significant difference in diabetic ITAs. Immunohistochemical examinations, scored on a 0 - 3 basis with 0 being the lowest (no reaction), 3 the highest (severe reaction), showed mostly no or slight reaction to CD34, CD68, Tenascin, and Collagen III for intima and media, with comparable results for diabetic or "irradiated" ITAs to those of the control group. The most distinct reaction (medium= 2), was detected for Collagen IV, a marker which outlines basement membranes of endothelia and smooth muscle cells of the vessel wall, but without differences between the four groups. No severe reactions were observed. CONCLUSIONS: The relative resistance of ITA to arteriosclerosis could be demonstrated in 227 ITA segments. Immunohistochemistry supports histomorphological findings. The influence of diabetes mellitus and irradiation remains irrelevant.

[Paleopathology of ancient Egyptian mummies and skeletons. Investigations on the occurrence and frequency of specific diseases during various time periods in the necropolis of Thebes-West]. / Paläopathologie altägyptischer Mumien und SkeletteUntersuchungen zu Auftreten und Häufigkeit spezifischer Krankheiten in verschiedenen Zeitperioden der altägyptischen Nekropole von Theben-West.

The scientific investigation of mummies and skeletons provides considerable data for the reconstruction of the living conditions and diseases of past populations. We describe the data on four completely analyzed tomb complexes from the huge necropolis of Thebes-West in Upper Egypt dating to different time periods. A total of 211 individuals from the so-called "Middle Kingdom" (MK, c. 2050-1750 BC) were compared to 273 individuals from the "New Kingdom" (NK) to "Late Period" (LP, in total 1550-500 BC). The age at death and the sex ratio were comparable between both groups. There was a high rate of early death with a maximum between the 2nd and 3rd decade of life but infant/adolescent burials were comparably rare. This early death is assumed to be due to an elevated prevalence of various infectious diseases. Likewise, a high rate of tuberculosis infections was seen in those individuals regardless of which time period they came from. Metabolic disorders with osseous manifestations, such as scurvy, osteomalacia and chronic anemia (cribra orbitalia, porotic hyperostosis) were found with a high frequency in the MK populations but significantly less in the NK-LP populations. On the other hand signs of trauma were comparably high, and lesions due to degenerative joint and vertebral diseases were significantly higher in LP than in MK or NK individuals suggesting a higher mechanical load in the later populations. Cases of malignant (secondary) bone tumors and various soft tissue/organ diseases indicate that "civilization" disorders were present when the living conditions assured survival into advanced age. In summary, we provide circumstantial evidence that the systematic and concise analysis of mummy and skeletal remains can allow a reconstruction of major aspects of life and disease in historic populations, although a complete reconstruction is not possible.

Nasopharyngeal epignathus causing nasal airway blocking in a 4-year old child.

Congenital oral teratoma or epignathus is a very rare lesion, especially in older children. We report on a 4-year old female infant presenting with nasal blocking, little watery discharge and recurrent otitis. First adenoids were suspected. An endoscopic examination of the nose and nasopharynx demonstrated an irregular mass in the nasopharynx, covered partly by mucosa. A MRI-scan (T1-weighted) showed fat-intensity. Histological examination revealed a teratomatous malformation. Although rare, teratoma should be included in the differential diagnosis of a nasopharyngeal mass in the paediatric age group.

[Leiomyoma of the glans penis]. / Leiomyom der Glans Penis.

Glans penis leiomyomas are uncommon as primary nonepithelial tumors of the urogenital tract. Only 4 cases are described until today. We saw an other case of an 12 years old boy with a leiomyoma of the glans penis. Clinically the lesion presented as a yellow induration with no symptoms as pain, pruritus or bleeding. The biopsy revealed histological a leiomyoma in the subcutis of the glans penis with no symptoms of malignancy. Because of suspected functional and cosmetic deficiency a total resection was not performed. None of the cases described in the literature showed in the follow up malignancy or recurrency. 18 months postoperatively our patient is furthermore well and without symptoms. Nevertheless the leiomyoma of that localization is rare, this tumor should be included in the differential diagnosis of the neoplasms of the glans penis.

Microsatellite instability and loss of heterozygosity in prostatic carcinomas: comparison of primary tumors, and of corresponding recurrences after androgen-deprivation therapy and lymph-node metastases.

BACKGROUND: The molecular mechanisms leading to prostate cancer progression are poorly understood. In particular, those changes which are responsible for androgen-independent growth and metastatic spread in prostate cancer are an issue of current investigations. METHODS: To gain more insight into these processes, paired microdissected samples from both untreated, locally advanced primary tumors (n = 20) and recurrences (n = 20) after conventional androgen-deprivation therapy (ADT) were analyzed retrospectively for microsatellite instability (MSI) and loss of heterozygosity (LOH) at nine loci on chromosomes 8, 18, and X by polymerase chain reaction. In parallel, 12 prostatic carcinomas treated by radical prostatectomy and nine corresponding lymph-node metastases were analyzed in the same way. RESULTS: The group treated with ADT showed a total of 10 MSI in 7 of the primary tumors (35%): 4 of these (20%) at one locus, and 3 of these (15%) at two loci. In the recurrences, MSI was observed in 4 cases (20%): 3 of these at one locus (15%), and 1 of these (5%) at two loci. LOH was found in 8 cases (40%) before as well as after ADT. In the radically resected carcinomas, MSI could be detected at two chromosomal loci in one of the primary tumors (8%) and in one of the metastases (11%); LOH was found in 2 primaries (16%) and 3 metastases (33%). CONCLUSIONS: Although MSI can be found in advanced prostatic carcinomas, it apparently does not play a major role in the progression of prostate cancer regarding androgen-independent growth or lymphogenous spread.

Microsatellite analysis in serous tumors of the ovary.

Thirty-four serous ovarian neoplasms were analyzed for microsatellite instability (MIN) and loss of heterozygosity (LOH) at 20 chromosomal loci of eight different chromosomes, including the map positions of the six known mismatch repair genes. Twelve of the 20 (60%) serous ovarian tumors of low malignant potential (LMP) and 13 of 15 (87%) samples of serous ovarian carcinomas, taken from 14 patients, showed LOH at one or more of the analyzed microsatellite loci. In serous carcinomas, LOH of the dinucleotide repeat D7S521 was most frequent. Six of 20 (30%) LMP tumors were also affected by MIN at more than one locus, whereas in the carcinomas MIN was found only sporadically (p < 0.025). No correlation between increased occurrence of MIN and LOH at the chromosomal loci of the known mismatch repair genes were discovered for these LMP tumors. Although our observation regarding LOH frequency in serous LMP tumors and serous carcinomas is compatible with the hypothesis that serous LMP tumors might represent precursor lesions of invasive carcinomas, the results concerning the occurrence of MIN suggest that the mechanisms of tumorigenesis of some tumors of LMP are distinct from those in invasive serous carcinomas.

In serous ovarian neoplasms the frequency of Ki-ras mutations correlates with their malignant potential.

We analysed 44 tissue samples from serous ovarian neoplasms of different malignant potential for Ki-ras mutations by denaturing gradient gel electrophoresis (DGGE) and direct sequencing after microdissection. Point mutations at codon 12 were found in 7 of 20 tumours of low malignant potential (LMP) (35%) and in 2 of 6 well-differentiated carcinomas (33%). In contrast, no mutations were detected in the 11 poorly differentiated ovarian carcinoma samples or in the 7 serous cystadenomas. The frequency of Ki-ras mutations in serous ovarian tumours seems to correlate with the malignant potential of the neoplasms. The data favour the hypothesis of a de novo development of poorly differentiated ovarian carcinomas and do not support an evolution from LMP tumours or well-differentiated carcinomas.

Malignant tumors in an ancient Egyptian population.

Since it is still an open debate whether malignant tumors are mainly influenced by environmental factors, the frequency of such malignant tumors in historic populations with different living conditions is of particular interest. In the present study, we investigated the occurrence of malignant tumors affecting bone tissue in a population of mumrnies and skeletons, which had been excavated from the large necropolis of Thebes-West, Upper Egypt. Our study material comprised a series of at least 415 individuals (thereof 325 adults) dating from approx. 1500-500 B.C. All individuals had been mummified, but were severely damaged and partially broken by grave robbers, so that often only parts of the mummies/skeletons were available for investigation. The available specimens were subjected to careful macroscopic examination, while isolated findings were radiologically analyzed. Using this approach, we identified at least 4 cases showing malignant tumors affecting the skeleton. In two cases, multiple mixed osteolytic-osteoblastic lesions suggested multiple metastases from carcinomas. Two further individuals presented with multiple osteolyses (vertebra, pelvis, skull) most suggestive of multiple myeloma. The observation of at least 4 cases of malignant tumors with osseous manifestation in a series of 325 adult individuals provides clear evidence that malignant tumors were not a rare event in the ancient Egyptian study population, particularly when the limitations of a study of tumors manifested only in osseous remnants are taken into consideration. A calculation of the age- and sex-adjusted tumor frequency in our material in comparison with a recent model for such a material by Waldron (1996) indicates that the rate of malignant tumors with bone affection in our series is higher than in an English population from 1901-1905, although lower than in a comparable present day population. This clearly indicates that important factors affecting malignant tumors were effective even in historic populations.

Defects of the respiratory chain in the normal human liver and in cirrhosis during aging.

Defects of the respiratory chain are a typical feature of mitochondrial diseases and occur also during normal aging where they have been described in postmitotic tissues. The present study addresses the question of defect expression in the normal and cirrhotic liver. Randomly distributed defects of complex III (ubiquinone-cytochrome-c-oxidoreductase) and of complex IV (cytochrome-c-oxidase) of the respiratory chain have been detected with age-related increasing frequency both in normal and cirrhotic livers. No defects were present for complex II (succinate-dehydrogenase) and complex V (adenosine triphosphate-synthase) and in liver cell carcinomas. Sixty-one of 107 normal livers (57%) showed defects of the respiratory chain. The defects occurred in advanced age (over 50 years) in 87%. In contrast 50 of 64 cirrhotic livers (78%) had defects and approximately 60% occurred after age 50. The defects were caused by a loss of enzyme protein involving both nuclearly and mitochondrially coded subunits. Ninety-four percent of the defects (n = 275) involved complex IV selectively. In 4% selective defects of complex III were found and combined defects of both complexes occurred in only 2%. In situ hybridization and polymerase chain reaction (PCR) studies for the detection of the common deletion (4.977 bp) and of various point mutations of mitochondrial DNA (mtDNA) revealed no consistent molecular genetic abnormalities in microdissected respiratory chain defective liver cell areas. Single point mutations at nt 3243 and/or 5692 were found only in 7 of 18 microdissected probes from 6 patients. The results show that defects of the respiratory chain occur already in normal livers most probably during cell aging and at a higher rate in cirrhosis. The random defect pattern favors a stochastic process, e.g., free radical damage. However, the role of mutations of mtDNA remains to be established.

Reduction of the incidence of rejection by adjunct immunosuppression with photochemotherapy after heart transplantation.

In this study, photochemotherapy (PCT) was used for adjunct immunosuppression in the first six months after heart transplantation (HTx). Fifteen patients after orthotopic HTx were included in the study; all received standard triple-drug immunosuppression including cyclosporine, azathioprine and glucocorticoids, but no adjunct therapy with mono- or polyclonal antibodies. The patients were divided into three groups: group I served as control with no additional treatment; group II received adjunct treatment with 10 courses of PCT (single-day treatments); and group III received 20 PCT courses since it was given each time on two consecutive days. PCT was started in both groups on day one after HTx; it was applied with a higher frequency in the early postoperative period and thereafter continued at four-week intervals for a total of 6 months. The photopheresis method for PCT included extracorporeal UVA irradiation of mononuclear cells that were treated with the photosensitive drug 8-methoxypsoralen (8-MOP) and subsequently retransfused to the patient. A new liquid form of 8-MOP was added directly to the buffy coat, resulting in reliable and sufficient drug levels in the cell suspension during the irradiation period; problems caused by oral application due to unpredictable variations in gastrointestinal absorption were thus prevented. Analysis of the total numbers of acute rejection episodes (AREs) within the first four weeks after HTx revealed a more impressive decrease by double PCT (group III, 3 AREs) than by single PCT (group II, 5 AREs) in comparison with the control (group I, 6 AREs). Over the total observation time (mean: 9.6 months), however, both PCT schedules reduced the total number of AREs observed in the control group (20 AREs) equally by more than 50% (9 AREs each in groups II and III) (P = 0.007). Furthermore, PCT treated patients had significantly fewer infections (6 infections in each group) than control group patients (15 infections) (P = 0.026); this, however, may be accounted for by the higher number of acute rejections in the control group and consequent increase in unspecific immunosuppression treatment. Our results suggest that PCT is a safe and effective method of adjunct immunosuppression that can be applied early in the postoperative period; it reduces the number of rejection episodes and does not increase the risk of infections.