[Ferritin and soluble interleukin-2-receptor in the diagnosis of fever of unknown origin]. / Ferritin und löslicher Interleukin-2-Rezeptor als Schlüsselbefunde bei unklarem Fieber.

UNLABELLED: HISTORY UND CLINICAL FINDINGS: Within a few weeks, two patients aged 16 and 75 years with fever of unknown origin were referred to the emergency unit. INVESTIGATIONS: Laboratory tests revealed increased aminotransferase levels, progressive cytopenia and an increase of inflammatory markers. In the older patient a rapid clinical detoriation with multi organ failure was observed. Progressively increasing levels of ferritin and soluble-interleukin-2-receptor levels led to the diagnosis of hemophagocytic lymphohistiocytosis, which was confirmed by bone marrow examination in the case of the younger patient. TREATMENT AND COURSE: Immunsuppressive treatment induced a clear improvement of clinical and laboratory findings and in the case of the older patient finally led to convalescence. CONCLUSION: Hemophagocytic lymphohistiocytosis is a rare but potentially fatal differential diagnosis, which should be considered in patients with fever and cytopenia.

[Laparoscopic splenectomy for sclerosing angiomatoid nodular transformation]. / Laparoskopische Splenektomie bei sklerosierender angiomatöser nodulärer Transformation.

Sclerosing angiomatoid nodular transformation (SANT) is a benign lesion of the spleen which can be cured by splenectomy. In the literature about 45 cases have been reviewed. Although it is defined by the morphological details, data regarding surgical therapy are scarce. To the best of our knowledge, a laparoscopic approach has not been published before. We investigated in one case of SANT the feasibility of a laparoscopic approach. Histological investigations confirmed the diagnosis of a SANT which was resected in toto. This report shows that the laparoscopic splenectomy is a feasible, safe and effective method for treatment of SANT.

Cystic pseudotumours in both upper ankle joints in gouty arthritis.

This case demonstrates a yet unreported clinical entity of bilateral tophaceous cystic lesions of the tibiotalar joints of an 37-year-old white male who presents with moderate painful swelling in both upper ankle joints for 2 years. Radiodiagnostic studies show cystic lesions in both upper ankle joints and the right talus considering neoplastic processes in the differential diagnosis. The incisional biopsy reveals chalk-like material of the intraosseous lesions which was pathognomonic for tophaceous gout. Antihyperuricemic medication led to a stagnation of growth of the lesions without a sign of osseous remodeling. However, due to limitation of discomfort, personal preferences and a lack of surgical options conservative treatment was maintained.

[Space-occupying lesions in the liver: incidence of adenocarcinoma metastases of unknown primary site]. / Unklare hepatische Raumforderungen: Häufigkeit von Adenokarzinom-Metastasen eines unbekannten Primärtumors.

BACKGROUND AND OBJECTIVE: The diagnostic approach to newly detected space-occupying lesions in the liver can be difficult and a histogenetic classification of the primary tumor is impossible in some cases. Such cases of metastatic disease without a detectable primary tumor are classified as cancer of unknown primary site (CUP). The incidence of this diagnosis depends on the clinical and histochemical methods used. It was the main aim of this study to analyze the true incidence of adenocarcinoma metastases of the liver with an unknown primary cancer after application of a standardized protocol of clinical and immunhistochemical diagnostic tests and a long-term follow-up. PATIENTS AND METHODS: Between January 2000 and January 2003 127 consecutive patients underwent diagnostic ultrasound-guided biopsy of a space-occupying lesion in the liver. Based on the histopathology and immunochemistry a well defined and individually adapted diagnostic algorithm was employed (endoscopy, imaging). RESULTS: 44 females and 83 males, median age 66.8 years, were enrolled into the study. Primary tumors of the liver were found in 21 cases and non-hepatocellular tumors (metastases) were documented in 106 patients, 82 of the latter (77%) had metastases of an adenocarcinoma. The further diagnostic approach was based on histochemistry, immunhistochemistry and imaging techniques, making possible a full diagnosis of primary tumor in a further 59 (72%) cases. Thus the incidence of an adenocarcinoma of the liver of unknown primary site was 23 of 127 cases (18%). CONCLUSIONS: Although there is a wide variety of modern diagnostic methods today, the histogenetic classification of hepatic metastases is not always possible. However, in the last few years diagnostic advances have occurred based on modern immunhistochemical methods. This immunhistochemical definition has made it possible to avoid an oppressive "overdiagnosis" and offer patients early and appropriate therapeutic options.

Follow-up after endoscopic snare resection of duodenal adenomas.

BACKGROUND AND STUDY AIMS: Premalignant duodenal polyps are considered to be rare. Recurrence after local excision is reported to be frequent, so many authors propose radical surgical treatment of these tumors. The aim of this study was to determine the long-term outcome after endoscopic resection of duodenal adenomas. PATIENTS AND METHODS: Between January 1990 and April 2003 we retrospectively evaluated a group of patients who presented with nonampullary duodenal villous tumors but who did not have a polyposis syndrome. RESULTS: Duodenal polyps were diagnosed in 21 patients during routine endoscopy during the study period. Of these, 18 patients (6 men, 12 women; median age 67, range 50 - 81), with a total of 20 duodenal adenomas, were enrolled into the study. The median size +/- SD of the tumors was 27.5 +/- 12 mm (range 8 - 50 mm). Of these 20 tumors, 18 adenomas were tubulovillous, one was tubulous and one was villous. Nineteen polyps were treated by snare excision and one adenoma was treated with argon plasma coagulation alone. Argon plasma coagulation was applied to polyps in six patients after snare excision during this initial treatment phase. The success rate for endoscopic adenoma removal after a 3-month interval was 55 %. After a median follow-up period of 71 months (range 22 - 151 months), 12 patients remained in remission. Local recurrences of the lesion occurred in five patients (25 %) and these were re-treated. None of the patients developed carcinoma during the follow-up period. CONCLUSIONS: Endoscopic snare excision of duodenal adenomas is an effective mode of treatment but an endoscopic surveillance program is mandatory in order to detect and treat recurrence.

Does Cytokeratin7/20 immunoreactivity help to distinguish Barrett's esophagus from gastric intestinal metaplasia? Results of a prospective study of 75 patients.

Barrett's esophagus is a recognized risk factor for the development of esophageal dysplasia and carcinoma. Unfortunately, gastric incomplete intestinal metaplasia arising in Short Segment Barrett's esophagus can be indistinguishable histologically on hematoxylin/eosin stains. Distinct patterns of CK 7 and CK 20 immunohistochemical expression have been demonstrated to be both highly sensitive and specific for Barrett's esophagus, but have not been found in gastric metaplasia. The aim of our study was to test whether immunostaining with CK 7/20 helps to distinguish between Barrett's epithelium and gastric incomplete metaplasia. Cases of long segment Barrett's esophagus, short segment Barrett's esophagus, and cases with a normal gastroesophageal junction, as well as specimens with gastric antral intestninal metaplasia, were examined: three patterns were defined. Barrett's pattern (superficial CK 20 staining; superficial and crypt CK 7 staining); gastric pattern (superficial and crypt staining of both markers); other patterns (different from Barrett and gastric types). Seventy-five patients were enrolled in this study, 26 with long segment Barrett's esophagus, 21 with short segment esophagus, 13 with intestinal metaplasia of the cardia, and 18 with antral intestinal metaplasia. The Barrett pattern showed a high specificity of 97%, but a sensitivity of only 30% in patients with short segment Barrett esophagus. Our results do not confirm the hypothesis that CK 7/20 immunostaining can be used for a reliable differentiation between incomplete intestinal metaplasia and Barrett's epithelium.

[Scrotal abscess with inguinal lymph node swelling in an 86-year-old man]. / Skrotalabszess mit inguinaler Lymphknotenschwellung bei einem 86-jährigen Patienten.

HISTORY AND ADMISSION FINDINGS: An 86-year-old patient presented to our clinic with increasing redness and swelling of the right scrotum and inguinal lymphadenopathy. Five and a half years before admission carcinoma of the bladder (pT1,G2) had been diagnosed and was treated with several transurethral endoscopic resections as well as repeated instillations of Bacille Calmette-Guérin (BCG) into the bladder. INVESTIGATIONS: Orchiectomy on the right side was performed. Histological analysis revealed a granulomatous inflammation consistent with a mycobacteriosis. Mycobacterium bovis BCG could be isolated from several sputum and urine specimens of the patient. DIAGNOSIS, TREATMENT AND COURSE: Tuberculostatic therapy was started soon after surgery. After seven weeks of treatment no more mycobacteria could be detected in sputum and urine control specimens. At a follow up after twelve months there was no evidence of recurrent disease. CONCLUSION: We describe the late manifestation of a BCG infection including the lungs and the urogenital tract. This is a rare complication with potentially serious consequences and requires rapid diagnosis and urgent treatment by a multidisciplinary team.

[Symptomatic pericardial effusion as initial manifestation of gastric signet ring cell carcinoma]. / Symptomatischer Perikardergussals Erstmanifestation eines Siegelringzell-Magenkarzinoms.

HISTORY: A 78-year-old woman presented at our hospital with palpitation, tachycardia and progressive dyspnea. The health history included the diagnosis of diabetes mellitus and chronic obstructive pulmonary disease. INVESTIGATIONS: The ECG showed atrial fibrillation, later changing with sinus rhythm and low voltage. The echocardiography revealed pericardial effusion. The cytology showed signet ring cells from the stomach. Endoscopic study revealed a 3 cm tumor in the posterior wall of the upper part of the body. The histopathological examination diagnosed cancer of diffuse type according to Lauren, with signet-ring cells. TREATMENT AND CLINICAL COURSE: After treating the atrial fibrillation a pericardial drainage was performed. The pericardiocentesis yielded 500 ml of serous fluid. In an echocardiogram after pericardial drainage, pericardial effusion was no longer present. During the clinical course the patient suffered a stroke and the chemotherapy could not be initiated. The patient died 2 months after diagnosis. CONCLUSION: Cardiac involvement with clinical manifestations and pericardial effusion may be associated with a malignant neoplasm. Echocardiography and pericardiocentesis are helpful for the diagnosis of cardiac metastases.

[DNA cytometric studies of Barrett mucosa]. / DNA-zytometrische Untersuchungen der Barrett-Mukosa.

BACKGROUND: Barrett's esophagus predisposes to cancer development. The diagnosis of dysplastic precursor lesions is impaired by problems of subjectivity. In the present study, DNA ploidy results of patients with Barrett's esophagus were related to the grade of dysplasia and to the progress of the disease. PATIENTS AND METHODS: In 61 patients with Barrett's esophagus, DNA ploidy was determined by image cytometry on imprints. All biopsies (n = 145) were histologically examined for dysplasia distinguishing between low- and high-grade dysplasia, and dysplasia-negative. RESULTS: A significant correlation (p < 0.001) between DNA ploidy and the grade of dysplasia was found, with 81% euploid DNA results in biopsies negative for dysplasia and 86% abnormal DNA patterns in biopsies with high-grade dysplasia. The subgroup of low-grade dysplasia showed a heterogeneous DNA ploidy. It is important to note that nearly 20% of biopsies classified dysplasia-negative contained abnormal single cells or abnormal stemlines regarding DNA content. In several cases, suspect DNA results caused a modified reclassification of dysplasia, and there were cases in which patients negative for dysplasia but positive for abnormal DNA ploidy developed dysplasia later on. CONCLUSION: In patients with Barrett's esophagus, DNA ploidy by image cytometry is a suitable additive method for histological evaluation of dysplasia. It seems to be helpful in identifying patients at risk, perhaps before the development of clear dysplasia.

[Hepatocellular adenoma confirmed by Doppler ultrasonography and laparoscopy]. / Das hepatozelluläre Adenom: Diagnosesicherung unter besonderer Berücksichtigung von Duplexsonographie und Laparoskopie.

CASE REPORT: A 46-year-old female patient presented for further investigation of an isolated liver lesion that was diagnosed by her physician by abdominal ultrasound and computertomography. The Doppler ultrasound (including a signal amplifier) could not differentiate the lesion so that a laparoscopy was performed. A hepatic adenoma was found which was confirmed by the histological examination of a directed liver biopsy. CONCLUSION: Signs and symptoms, diagnostic procedures and differential diagnostic options of a hepatic adenoma are discussed.

Ras gene mutations in vinyl chloride-induced liver tumours are carcinogen-specific but vary with cell type and species.

Previous studies have shown that a high proportion (5/6) of human liver angiosarcomas (ASL) associated with exposure to vinyl chloride (VC) contains a GC-->AT mutation at the Ki-ras codon 13. This mutation, however, has not been found in 5 ASL or 2 hepatocellular carcinomas (HCC) induced in rats by VC. These 2 HCC did contain a mutation at codon 61 of the Ha-ras gene. In order to extend this study and further explore the mechanisms of tumour induction, an additional 6 ASL and 6 HCC induced in rats by VC were analysed for ras gene point mutations, as well as 10 rat and 10 murine ASL induced by vinyl fluoride (VF), and 5 ASL, 6 Kupffer cell sarcomas, 4 HCC and 2 cholangiocellular carcinomas induced by Thorotrast in rats. Tumour DNA was analysed by PCR-SSCP and direct sequencing. None of the rodent ASL contained a mutation at codon 13 of the Ki-ras gene showing that the ras gene mutational pattern is species-specific. The CAA-->CTA mutation, previously found at codon 61 of the Ha-ras gene in rat HCC, was observed in 5 further VC-induced HCC but was not detected in the Thorotrast-induced HCC, suggesting carcinogen-specificity. This mutation was also absent in VC-induced ASL, which supports the cell-specificity of the ras mutational pattern in chemically induced tumours. No predominant mutation was detected in VF- and Thorotrast-induced tumours. Thus, a given mutation in a tumour may be carcinogen-specific but also depend on the species and the cell type.

Relationship of DNA ploidy to hormone receptor status and proliferation in invasive breast carcinoma.

PURPOSE: In 247 primary invasive breast carcinomas, DNA ploidy was related to hormone receptor status, proliferation, and clinical/histopathologic factors. METHODS: DNA ploidy analysis was performed by image analysis using imprints. Estrogen (ER) and progesterone (PR) receptor status was determined immunohistochemically. The proliferative activity of the tumours was assessed by Ki-67 antigen labelling. Total observation time was 3.5 years. RESULTS: DNA ploidy analysis revealed a high fraction of tumours with non-peridiploid patterns (78%). Significant correlations between DNA ploidy and ER/PR receptor status (P < 0.01) were found with increased frequencies of peridiploid DNA results in receptor positive tumours. A significant relationship became manifest between DNA ploidy and Ki-67 index showing high frequencies of non-peridiploid DNA patterns in tumours with Ki-67 index > 20% (P < 0.01). There was a strong correlation (P < 0.001) between DNA ploidy and histopathologic grading, while tumour size and lymph node status were not correlated to DNA ploidy. CONCLUSIONS: The results of our study on invasive breast carcinoma demonstrate that DNA ploidy measured by image analysis is predominantly associated with markers of cell differentiation. Preliminary outcome data reveal a risk-indicating potential of DNA ploidy primarily in cases with favourable results for other prognostic factors.

German uranium miner study--historical background and available histopathological material.

Mining activities in the former German Democratic Republic were documented as early as 1168 in the ore mountains (Erzgebirge) of Saxony. Silver, bismuth, cobalt, nickel and tungsten were mined from then up to the end of the 19th century. After the Second World War, the Soviet Occupation Authorities reopened the old silver mines in Saxony to mine uranium for the Soviet nuclear industry. About 400, 000 workers produced a total of 220,000 tons of uranium during the years 1946 to 1990. After the reunification of Germany, the archive of the Institute of Pathology of the mining area was opened for research. It contains protocols of 28,975 autopsy cases and about 400,000 slides collected from 1957 to 1992, about 66,000 tissue blocks, and 238 whole lungs. From the autopsy cases, 17,466 could be identified as workers of the uranium mining company. The remainder of the cases were in the population of the mining area. A comparison of the frequencies of malignancies of male workers older than 15 years with those of the population of the mining area for the years 1957 to 1989 demonstrates a significantly higher percentage of lung cancer among the uranium miners. There was no significant difference for other solid cancers and leukemias.

German uranium miner study--pathological and molecular genetic findings. German Uranium Miner Study, Research Group Pathology.

Uranium miners of the former Wismut company in Germany form the largest cohort of workers exposed to (222)Rn and dust in the world. The German Uranium Miner Study, Research Group Pathology, is evaluating the central pathology archive of the Wismut company. The main tasks of our study are pathological-anatomical and molecular genetic investigations of 28,975 autopsy cases and the evaluation of mining pollutants in the lungs by neutron activation analysis. As part of an observer agreement study, lung tumors are classified according to the WHO/IASLC classification and nontumorigenic lung disorders are registered. Lung tumors were analyzed for the presence of a proposed radon-specific mutation in the TP53 gene (formerly known as p53). Interim results are: (a) In the years 1957 to 1965, a high rate (69%) of small cell carcinomas was found which had declined to 34% by 1990. (b) The percentage of the deceased who suffered from silicosis is not higher in the group of lung tumors than in other tumor groups or the nontumor group. (c) The hypothesis of a radon-characteristic hotspot mutation in the TP53 tumor suppressor gene is not supported by our investigations. (d) Neutron activation analysis demonstrates that uranium, arsenic, chromium, cobalt and antimony can be found in tissue samples from the miners even when they had stopped working more than 20 years before death.

The german thorotrast study: recent results and assessment of risks.

The German Thorotrast study comprises 2,326 patients and 1,890 controls. Forty-eight Thorotrast patients and 239 controls are still alive and are invited for a follow-up examination every 2 years. In the deceased patients, the following neoplastic diseases with excess rates were registered (Thorotrast/controls): liver cancer (454/3); cancer of the bile ducts, including gallbladder (42/7); myeloid leukemia (40/7); myelodysplastic syndrome (30/4); plasmacytoma (10/2); non-Hodgkin's lymphoma (15/5); bone sarcoma (4/1); malignant peritoneal or pleural mesothelioma (9/0). Dose calculations are based on results of whole-body counting, X-ray films, and data obtained from the hospital records on the volume of Thorotrast injected. For liver cancer, the cumulative risk estimate was calculated to be 40 per 10(4) person Sv (radiation weighting factor = 20). These figures are close to the results of the Danish study and are comparable to the results of the Life Span Study of A-bomb survivors after 40 years at risk with 18 to 48 liver cancers per 10(4) person Sv. For hematopoietic malignancies, the cumulative risk was calculated to be about 7 per 10(4) person Sv (radiation weighting factor = 20). This risk estimate is lower by a factor of 10 compared to the results of the Life Span Study.

[Treatment of Barrett esophagus with argon plasma coagulation with acid suppression--a prospective study]. / Behandlung des Barrett-Osophagus mit Argonplasmakoagulation unter Säuresuppression--eine prospektive Studie.

26 patients with a Barrett's esophagus of at least 2 cm length (medium 4.9 cm) were treated with a combination of repeated argon-plasma-coagulation (APC) and a long-term acid suppression using proton pump inhibitors controlled by a 2 h pH monitoring. Eleven out of 26 patients (42%) showed endoscopically and histologically a complete eradication of the metaplastic cylindric epithelium (intention--to treat analysis). Nine patients (35%) had an endoscopic complete remission but remnants of the cylindric epithelium were found at the histologic examination. On an average one APC-session was necessary for 1 cm of initial length of the Barrett's esophagus. No serious complications were seen. It remains unclear if this therapy can reduce the long-term risks for adenocarcinoma of the esophagus in patients with Barrett's esophagus.

[A rare cause of iron deficiency anemia: recurrent hemorrhage from a carcinoid of the jejunum--diagnosis and therapy with enteroscopy]. / Seltene Ursache einer Eisenmangelanämie: rezidivierende Blutung aus einem Karzinoid des Jejunums--Diagnostik und Therapie mittels Enteroskopie.

We report a 66-year-old patient with previously diagnosed iron deficiency anemia. He complained of fatigue, but had no further symptoms. Hemoglobin was 9.1 g/dl. Test for occult blood in stool was positive, but gastroduodenoscopy and colonoscopy revealed no bleeding source. The man was referred to our department for push-type enteroscopy. By enteroscopy we diagnosed a pedunculated, large polyp in the upper jejunum. The polyp seemed to be submucosal, but had some ulcerations on its surface as the probable bleeding source. In the lower parts of the small intestine no further polyps were detected. After endoscopic doppler examination we injected adrenaline into the base of the polyp to prevent bleeding and the polyp was removed by snare without complications. The polyp was diagnosed to be a carcinoid and was removed in sano.

[Barrett esophagus with severe dysplasia in argon beam therapy]. / Barrett-Osophagus mit schweren Dysplasien unter Argon-Beamer-Therapie.

A curative therapy of Barrett's esophagus is not established, yet. However, in prospective clinical research trials, a combined therapy of potent pharmacological acid suppression with superficial coagulation of metaplastic epithelium is examined. By local coagulation using photodynamic therapy, laser or argon plasma coagulation, a complete reconstitution of squamous epithelium should be achieved. We report on a case of a patient with Barrett's esophagus and low-grade dysplasia, who developed high-grade dysplastic cell formations under argon plasma coagulation therapy. As part of a clinical study, the patient was treated over a period of one year monthly. We monitored the result of the therapy over the period of one year with endoscopy, histolgical investigations and DNA image cytometry. Ultimately a decision in favour of a further surgical management was made. The diagnostic instruments to identify patients with a high risk for the development of adenocarcinoma are discussed.

p53 gene mutation analysis in tumors of patients exposed to alpha-particles.

The p53 gene was examined for point mutations in archived, alpha-radiation-associated lung and liver cancers. Lung tumors of 50 uranium miners in Germany were screened by restriction fragment length analysis for the putative hotspot mutation at codon 249 (Arg-->Met) previously detected in a significant fraction of miners from the Colorado Plateau, USA. This mutation has been proposed as a marker of radon exposure. None of the tumors we examined harbored the hotspot mutation. Five of the 50 tumors, however, did indeed harbor exon 7 mutations, as determined by subsequent mutation analysis of exon 7. These mutations were dispersed among various codons and may be attributable to heavy tobacco smoking in this cohort. In support of this interpretation, we found no mutations in exons 5-8 of the p53 gene in 13 iatrogenic liver cancers induced by injection of Thorotrast, an alpha-emitting radiocontrast agent. We propose that if the p53 tumor suppressor gene is a target for the carcinogenic action of alpha-particle radiation, loss of suppressor function may occur preferentially by mechanisms such as intrachromosomal deletions, rather than by base substitution mutations.