[Unexpected deposits in the upper gastrointestinal tract : When medical history matters]. / Unerwartete Ablagerungen im oberen Gastrointestinaltrakt : Wenn es ohne klinische Angaben nicht weitergeht.

In order to regulate their phosphate uptake, patients with end-stage renal disease rely on phosphate binders such as lanthanum carbonate (LC). The earliest histopathological reports of this rare entity in the gastrointestinal mucosa were described and published in 2015.We present a case of an 80-year-old patient with LC gastro-enteropathy. Histopathologically it can mimic other drug-induced depositions and even infectious or neoplastic entities. Evaluation of the patient's medical and especially drug history is essential to obtain the appropriate diagnosis. We present an overview of the clinical presentation and histological differential diagnosis of LC.

[Digital pathology : The time has come!] / Digitale Pathologie : Die Zeit ist reif!

BACKGROUND: Digital pathology (DP) and whole-slide imaging (WSI) technology have matured substantially over the last few years. Meanwhile, commercial systems are available that can be used in routine practice. AIMS: Illustration of DP experiences in a routine diagnostic setting. RESULTS AND CONCLUSIONS: A DP system offers several advantages: 1) glass slides are no longer unique; 2) access to cases is possible from any location; 3) digital image analysis can be applied; and 4) archived WSI can be easily accessed. From this point, several secondary advantages arise: a) the slide compilation of the case and the case assignment is fast and safe; b) carrying cases to the pathologist is obsolete and paperless work is possible; c) WSI can be used for a second opinion and be accessible in remote locations; d) WSI of referred cases are still accessible after returning the slides; e) histological images can easily be provided in tumor boards; f) the office desk is clean; and g) a "home office" is possible. To introduce a DP system, a comprehensive workflow analysis is needed that clarifies the needs and wishes of the respective institute. In order to optimally meet the requirements, open DP platforms are of particular advantage, because they enable the integration of scanners from various manufacturers. Further developments in image analysis, such as virtual tissue reconstruction, could enrich the diagnostic process in the future and improve treatment quality.

Sodium taurocholate co-transporting polypeptide deficiency.

INTRODUCTION: Little is known about bile acid transporter defects on the basolateral side of hepatocytes. In 2015 Vaz et al. published a first case of SLC10A1 mutation causing Na-taurocholate Co-transporting Polypeptide deficiency with hypercholanemia and normal bilirubin and Autotaxin levels. The index patient presented with failure to thrive, but without pruritus or jaundice. Several new cases have been published since, but the full spectrum of clinical presentation of mutations in SLC10A is not known. The primary aim of this review is to report a patient with a novel homozygous mutation and discuss the findings in the light of all other reported cases to date. MATERIAL AND METHODS: We describe the findings of a patient with a previously unreported homozygous mutation and review all published cases to date in English on PubMed. RESULTS: Our female patient born in 2002 presented with a feeding disorder and failure to thrive akin to the first description by Vaz. Workup suggested underlying liver disease although she did not complain of pruritus. Serum levels of aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and bilirubin were normal. Plasma bile acids were chronically elevated, up to 150-fold. A first liver biopsy performed at 2 years of age showed unspecific findings with focal steatosis. Ursodeoxycholic acid treatment was introduced and the liver panel monitored regularly. At age 14, a second biopsy was performed, and histology was within normal limits. At this time, serum Autotaxin levels were found to be in normal range. Finally, genetic analysis revealed a homozygous 5 bp deletion in the gene SLC10A1 resulting in a premature stop codon predicted to lead to a complete NTCP loss of function. Most other reported cases to date carry the c.800C>T (p.Ser267Phe) mutation and are asymptomatic. DISCUSSION: NTCP deficiency appears to have a benign course as most patients are asymptomatic. Many patients seem to present with transient neonatal jaundice. Large variations in total plasma bile acid levels are observed between patients; they may be linked to the underlying genetic mutation or to yet uncharacterized compensatory mechanisms. Longer follow-up is needed to evaluate the long-term consequences of this newly identified inherited disease of bile acid transport.

Coronary Heart Disease and an Incidental Parathyroid Carcinoma.

A 71-year-old woman was admitted with angina pectoris. During hospitalization she developed a myocardial infarction (NSTEMI). Laboratory results revealed a mild elevated troponin and an elevated calcium level (3.35 mmol/l). Subsequently, there was a decreased phosphate (0.36 mmol/l [normal 0.81-1.62 mmol/l]) as well as 16-fold elevated serum level of parathyroid hormone (PTH, 1156 ng/l [normal 10-73 ng/l]), indicating a primary hyperparathyroidism. Sonographically a thyroidal node was detected, not clearly demarcated (TIRADS 5). FNA showed a monomorphic, partial follicular cell population with an immunohistochemical positivity for PTH. Magnetic resonance imaging (MRI) showed a 5 cm large tumor at the right caudal pole of the thyroid with compression of the dorsolateral trachea without infiltration. Surgical removal with en bloc resection of the right hemithyroid with parathyroidectomy was performed. Postoperatively the PTH level dropped to 12.1 ng/l. Pathological examination revealed a 5 cm tumor with infiltration of the thyroid and a perineural invasion. The diagnosis of a presymptomatic parathyroid carcinoma could be established. The affirmative histopathological diagnosis of a parathyroid carcinoma can be challenging and is limited to tumors with evidence of invasive growth in adjacent structures such as the thyroid and/or soft tissue, perineural spaces, angioinvasion of capsular and/or extracapsular vessels, and/or documented metastases.

Submucosal cushioning with water jet before endoscopic mucosal resection : Which fluids are effective?

BACKGROUND: Several new techniques have recently been described that allow the endoscopic mucosal resection even of broad-based flat lesions in the gastrointestinal tract. The technique recently described by us of using a water jet dissector (Helix HydroJet) for a selective deposition of liquid in the submucosal lamina has now been combined with different substances, and their effects have been compared. MATERIAL AND METHODS: Gastroscopies were carried out in 8 pigs under intubation anesthesia, and 2 submucosal cushions each were created in the stomach using one out of 4 test substances (gelatin, glucose 50, hydroxyethyl starch [HES] 10%, dextran 40), as well as one cushion of isotonic saline solution placed in each area via the Helix HydroJet). The height of the submucosal cushions was intermittently measured over a period of 40 or 20 min, respectively, by miniprobe endosonography. In 7 of the animals the stomach was subsequently subjected to mucosal resection. The specimens and the gastric wall were histologically assessed to evaluate the localization of the liquid cushion and the effect on adjacent layers of the gastric wall. RESULTS: All test substances produced strictly selective liquid cushions in the submucosa. With HES 10% and dextran the maximum height of the cushions initially increased and then decreased during the further course to an average of 90% of the initial height within 40 min. Isotonic saline solution showed the most rapid decrease in height (72% after 20 min). The histological assessment confirmed the selective nature of the liquid deposit in the submucosa. DISCUSSION: Plasma expanders produced cushions that initially increased in height but then remained constant for a longer period than cushions produced using glucose 50, gelatin, or isotonic saline solution. The combination of transmucosal jet application for elevation of the mucosa with plasma expanders is therefore an interesting approach to optimize endoscopic mucosal resections.

[Development of a three-dimensional primary prostate cancer cell culture model]. / Entwicklung eines dreidimensionalen Prostatakarzinomzellkulturmodells.

Much prostate cancer research is based on cell culture results. Recent genomic studies found major differences between primary prostate cancer tissue and established prostate cancer cell lines, which calls into question the clinical relevance of study results based on cell cultures.Using primary cultures of prostate cancer cells from prostatectomy specimens seems to be a reasonable solution, but primary cell cultures are much more difficult to establish. In this study, a primary cell culture model was combined with an invasion assay. With this combination it was possible not only to select invasive cell clones from the primary culture but also to culture these cells in a three-dimensional model, forming spheroids. A further characterization of this cell population was done by comparative genomic hybridization, showing numerous genetic alterations. The presented cell culture model offers, for the first time, an opportunity to isolate invasive growing cells from primary prostate cancer tissue and cultivate these cells for further analyses.

Sterilized mosquito net versus commercial mesh for hernia repair. an experimental study in goats in Mbarara/Uganda.

BACKGROUND: In industrialized countries alloplastic meshes are routinely used for hernia repair. However, in developing countries they are rarely available or affordable. This study compares textile properties and tissue response of commercial polypropylene mesh (PM) vs. sterilized nylon mosquito net (MN). METHODS: Textile properties were examined in vitro. In 12 goats one MN and one PM (5.5 x 8 cm) were implanted onto the posterior layer of the rectus sheath. Wound healing was clinically assessed. Histology was assessed after 4 or 16 weeks. RESULTS: MN was thinner and lighter, but weaker than PM. All wounds healed without complications. After 16 weeks foreign body granulomas in the MN group contained a higher proportion of inflammatory tissue (32.7 vs. 22.1%) and more giant cells (3.1 vs. 1.7/10 granulomas) with a significantly lower partial volume of foreign body (23.2 vs. 36.9%). Partial volume of fibrotic tissue was similar. MN was 1,000-fold cheaper than PM. CONCLUSIONS: PM was superior concerning strength and extent of inflammatory response. However, the findings indicate that MN might serve as a cheap substitute if an alloplastic mesh is needed but no commercial one is available or affordable. Further studies are justified which should include mosquito nets of different materials and long-term outcome.

[Optimized standards for prostate biopsy]. / Optimierte Standards der Prostatastanzbiopsie.

As individual risk assessment mainly depends on the correct prediction of the tumor's biological behavior, primary diagnosis plays a key role in the clinical management of prostate cancer patients. Prostate core needle biopsy, as a primary diagnostic tool, should not only confirm clinical suspicion but also supply the urologist with information which is necessary for risk-adapted therapy. The experience and competence of both the urologist and the pathologist are crucial for the quality of prostate core needle biopsy diagnosis. Optimized handling and submission of prostate core needle biopsy specimens by the urologist to the pathologist are of outstanding importance for improving the number of cancer cases detected. Increasing availability of molecular markers leads to the necessity of developing new tissue sampling procedures which allow prostate core needle biopsy specimens to be simultaneously studied histologically and by molecular approaches.

Overexpression of a member of the pentraxin family (PTX3) in human soft tissue liposarcoma.

A unique feature of human soft tissue liposarcoma is a stable (12;16)(q13;p11) translocation observed mainly in myxoid and roundcell liposarcomas. This translocation results in FUS/CHOP fusion transcripts with a corresponding oncogenic protein. We hypothesised that genes downstream of FUS/CHOP might serve as attractive candidates for novel tumour associated antigens. Among a panel of analysed genes, only pentraxin related gene (PTX3) demonstrated high expression in liposarcomas as compared to normal tissues. The analysis of RNA and protein expression demonstrated concordant results. However, the level of RNA and protein overexpression did not correlate in all cases. Finally, PTX3 expression was not related to presence of a FUS/CHOP fusion transcript within the liposarcoma tissues. PTX3 has been associated with adipocyte differentiation and now, additionally, is characterised by a markedly increased expression in human soft tissue liposarcoma. This finding mandates further research efforts to clarify the exact role of PTX3 in liposarcoma oncogenesis.

[Malignant mesothelioma of the testes]. / Das maligne Mesotheliom des Hodens.

INTRODUCTION: Malignant mesothelioma of the tunica vaginalis is a very rare malignant tumour. The prevalence of mesothelioma is about 1 : 1 000 000: Only 1 % have their origin in the tunica vaginalis testis with a 5-year survival of less than 5 %. About 80 cases have been reported in the literature. In 41 % of these cases exposure to asbestos for many years was determines. CASE REPORT: We report on a 76-year-old patient who presented with an atypical hydrocele testis. Intraoperatively, thickened testicular walls and an crystalline lawn adjacent to the tunica vaginalis testis were found. CONCLUSIONS: Ultrasonography showing snow flurries together with cloudy hydrocele fluid and visible crystal particles and thickened testicular walls may help to identify a mesothelioma of the testicular walls. Intraoperative frozen section and a high inguinal orchiectomy is the operative method of choice.

[Scrotal lymphangioma--a rare cause of acute scrotal pain in childhood]. / Das skrotale Lymphangiom--eine seltene Ursache des akuten Skrotums im Kindesalter.

INTRODUCTION: Scrotal lymphangioma is a rare differential diagnosis in boys with acute scrotal pain. CASE REPORT: A 5-year-old boy presented with acute scrotal pain and swelling. Physical examination demonstrated an unusual cystic scrotal mass with a normal testis. Ultrasound and MRI showed a complex septated cystic mass. The tumor was excised completely via an inguinal and scrotal approach. 2-year follow-up examinations with physical examination and ultrasound have shown no evidence of recurrence. CONCLUSIONS: Scrotal lymphangiomas are commonly misdiagnosed preoperatively. When ymphangioma is suspected, ultrasound and MRI imaging of the adjacent inguinal, perineal and pelvic region should be performed. To prevent recurrence, complete surgical excision is mandatory.

Reduction in the expression of glucose transporter protein GLUT 2 in preneoplastic and neoplastic hepatic lesions and reexpression of GLUT 1 in late stages of hepatocarcinogenesis.

Expression of two important glucose transporter proteins, GLUT 2 (which is the typical glucose transporter in hepatocytes of adult liver) and the erythroid/brain type glucose transporter GLUT 1 (representing the typical glucose transporter in fetal liver parenchyma), was studied immunocytochemically during hepatocarcinogenesis in rats at different time points between 7 and 65 wk after cessation of 7-wk administration of 12 mg/kg of body weight of N-nitrosomorpholine p.o. (stop model). Foci of altered hepatocytes excessively storing glycogen (GSF) and mixed cell foci (MCF) composed of both glycogenotic and glycogen-poor cells were present at all time points studied. Seven wk after withdrawal of the carcinogen, GSF were the predominant type of focus of altered hepatocytes. Morphometrical evaluation of the focal lesions revealed that the number and volume fraction of GSF increased steadily until Wk 65. MCF were rare at 7 wk, increased slightly in number and size until Wk 37, but showed a pronounced elevation in their number and volume fraction from Wk 37 to Wk 65. In both GSF and MCF, GLUT 2 was generally decreased or partially absent at all time points. Consequently, foci of decreased GLUT 2 expression showed a steady increase in number and volume fraction from Wk 7 to Wk 65. GLUT 1 was lacking in GSF but occurred in some MCF from Wk 50 onward. The liver type glucose transporter GLUT 2 was decreased in all adenomas and hepatocellular carcinomas (HCC). In three of seven adenomas and 10 of 12 carcinomas, expression of GLUT 1 was increased compared with normal liver parenchyma. In two cases of adenoid HCC, cells of ductular formations coexpressed GLUT 2 and GLUT 1. In contrast, normal bile ducts, bile duct proliferations, and cystic cholangiomas expressed only GLUT 1. Seven of 12 HCC contained many microvessels intensely stained for GLUT 1, a phenomenon never observed in normal liver. Whenever adenoid tumor formations occurred, GLUT 1-positive microvessels were located in the immediate vicinity of these formations. Only in one HCC were such microvessels found in the absence of adenoid formations. Our studies indicate that a reduction of GLUT 2 expression occurs already in early preneoplastic hepatic foci and is maintained throughout hepatocarcinogenesis, including benign and malignant neoplasms. Reexpression of GLUT 1, however, appears in a few MCF and in the majority of adenomas and carcinomas.

Fas ligand expression in Hodgkin lymphoma.

Because previous investigations suggested involvement of the Fas ligand (FasL) in the selection process in the follicular dendritic cell (FDC)-associated cell cluster of the germinal center, we investigated the expression of FasL in Hodgkin lymphoma (HL) on protein and RNA level, while considering the Epstein-Barr virus status of the Hodgkin and Reed-Sternberg (HRS) cells. Tumor tissue from 47 patients with classic HL (32 nodular sclerosis [NS], 11 mixed cellularity [MC], and 4 lymphocyte-rich [LR]) was analyzed by immunohistochemistry for FasL, Fas, CD21, and CD23 and by Western blotting for FasL. FasL mRNA was detected by an exon 4-specific oligonucleotide and Epstein-Barr virus infection by in situ hybridization for Epstein-Barr virus early RNAs (EBER). Western blotting showed soluble and membrane-bound forms of FasL. Immunohistochemistry showed FasL expression in virtually all HRS of 94% of NS cases and 82% of MC cases. FasL expression did not correlate with the Epstein-Barr virus status of the HRS. Low FasL protein expression was found in some HRS of LR cases. FasL mRNA was detected in 39% of NS, 46% of MC, and 33% of LR cases. Seventy percent to 90% of the HRS cells expressed Fas. CD21 immunohistochemistry showed disrupted FDC networks in the tumor tissue with reduced and virtually absent expression of CD23 and FasL. These observations suggest that FasL expression in HRS cells and the absence of FasL in the FDC cluster represent a disturbed microenvironment that may be involved in the pathogenesis of HL.

Both atrial resection and superior vena cava replacement in sleeve pneumonectomy for advanced lung cancer.

Extended sleeve pneumonectomy including removal of the superior vena cava, right atrium and parts of left atrium on cardiopulmonary bypass was successfully performed in a 40-year-old man. The tumour was histologically proven a T4 N1 stage with margins free from tumour. Adjuvant radiochemotherapy was administered postoperatively on an outpatient base. The patient did well for 7 months then he died from myocardial infarction due to metastatic infiltration of the right coronary artery. Other metastatic deposits were not found at autopsy. More data from extended pulmonary resections are required to demonstrate a benefit.

FatalAspergillus fumigatus septicemia in a patient with an ectopic ACTH-producing neuroendocrine pancreatic tumor.

The case of a 71-yr-old Caucasian patient who suffered from an adrenocorticotropic hormone (ACTH)-producing tumor and developed a fulminantAspergillus fumigatus septicemia is reported. The patient presented initially with a recent onset of hyperglycemia and had excessive plasma levels of cortisol and ACTH. A computer-assisted tomography scan showed a tumor associated within the head of the pancreas. During his hospital course, he developed a rapid progressive fatalAspergillus fumigatus pneumonia and an upper gastrointestinal bleeding. At necropsy multiple abscesses in the brain, lungs, heart, kidneys, small bowel and mesentery were present as a result of Aspergillus septicemia. A neuroendocrine pancreatic tumor, 8 cm in diameter, was found in the head of the pancreas without any signs of malignancy. The tumor showed immunohistochemical and electron microscopic evidence of ACTH expression, but of no other pituitary or pancreatic hormones. This case demonstrates the fulminant progress of a septicemia based on an immunologically compromised patient because of ectopic Cushing's syndrome. Early diagnosis of ectopic ACTH syndromes is essential for adequate therapy in order to prevent complications and fatal infections.

Correlation between neovascularisation and neuroendocrine differentiation in prostatic carcinoma.

Neuroendocrine (NE) differentiated tumor cells are found in almost all prostatic carcinomas. Prostatic carcinomas with a high NE differentiation have a poor prognosis and increased metastatic potential. A relationship between the neovascularisation density in the tumor and the metastatic potential in prostatic carcinoma is well known. NE cells and microvessels were demonstrated immunohistochemically on 102 radical prostatectomy specimens using antibodies against Chromogranin A and CD34. Standard areas (7.9 mm2) of maximal Chromogranin A expression and highest vascularisation were determined and topographically related by light microscopy. Area density of microvessels was evaluated morphometrically. NE tumor cells were present in all prostatic carcinomas studied. High grade prostatic carcinomas expressed significantly more NE tumor cells and exhibited a higher neovascularisation than low grade carcinomas. There was significantly higher neovascularisation in high grade tumors with many, as compared to high grade tumors with few, NE tumor cells. Poorer pathological staging correlated with increased neovascularisation and stronger NE differentiation. A topographical relationship between the area of maximal NE tumor cells and the area of highest neovascularisation was found in 80.4% of all cases. An analysis of variance revealed a large number of NE tumor cells as the only predictor of an increased neovascularisation (p = 0.0006). These observations support the concept that increased neovascularisation is influenced not only by poor pathological grading but also by a high NE differentiation.

Polo-like kinase: a novel marker of proliferation: correlation with estrogen-receptor expression in human breast cancer.

Previous data have shown that the mRNA-expression of the serin/threonine-kinase polo-like kinase (PLK) is closely correlated with the survival of patients suffering from a subset of malignant tumors. PLK-mRNA and protein-expression are restricted to cells in the cell cycle. PLK-mRNA-transcripts are highly abundant in proliferating cells; no gene expression is found in G0-phase cells. Here we investigated the mRNA- and protein-expression of PLK- and estrogen-receptor (ER) in human breast-carcinoma by northern-blotting, RT-PCR and immunohistochemistry. The expression of MIB-I was determined on serial sections. Analysis of the immunohistochemical data revealed a close correlation between the ER and PLK-expression (r = 0.677; p = 0.001, n = 30). No relationship between the mRNA-expression of ER and PLK was found. Furthermore, no correlation for the protein expression of PLK and MIB-I exists. The influence of estrogen (ES) is known to have proliferative potential. The expression of ER correlates with the ES-plasma-level. In addition, the hormone cycle of premenopausal women undergoes rapid vacillations with varying effects on the proliferating tumor cells, e.g., growth induction. Our results therefore show that ER-expression is not only of therapeutic value for the clinician, but it may also be a tool for determining the tumor proliferation index more precisely by integrating the hormone-mediated proliferation stimulus.

Atraumatic intracutaneous skin closure with self-made fishing line suture compared to commercial thread.

OBJECTIVE: The aim of this study was to prove, whether the intracutaneous skin closure with self made fishing line suture is equivalent to commercial sutures. DESIGN: It was a randomised blinded animal study. SETTING: The study was performed in December 2002 at the Muhimbili University College of Health Sciences in Dar-es-salaam. SUBJECTS: Both German surgeons from Mannheim, and Tanzanian surgeons from Dar es salaam operated on nine one year old Tanzanian domestic sheep. INTERVENTIONS: 108 standardised cutaneous wounds on the backs of the animals were closed by intracutaneous sutures either with self produced fishing line suture or a commercial nylon suture (Ethilon). MAIN OUTCOME MEASURES: The clinical and histological outcomes, as well as the costs of this self-made fishing line suture, with a commercial nylon thread were evaluated and compared. RESULTS: There are no significant differences between the two sutures in histological or clinical findings, or in the reported ease of use by the surgeons. The cost of a self-produced atraumatic thread is US$ 0.12, less than one-twentieth of the cost of the commercial thread. CONCLUSION: Self-made fishing nylon suture has characteristics and properties in sheep skin wounds comparable to commercial nylon suture. The advantage of the commercial thread is the guaranteed quality assurance. It is discussed whether this quality assurance justifies the large price difference, and whether the self-produced thread should be recommended to surgeons in countries where the costs of surgical material often remains an obstacle for life saving operations.

[Fibromyxoid pseudosarcoma of the urinary bladder. Case report and review of the literature of a rare disease]. / Das fibromyxoide Pseudosarkom der Harnblase. Fallbericht und Literaturübersicht einer seltenen Erkrankung.

Pseudosarcomatous fibromyxoidtumors (PSF) of the bladder are rare, benign tumors consisting of myofibroblastoid bladder wall proliferations of unknown etiology. Misinterpretation as a sarcoma is common and due to infiltrative growth and cellular pleomorphism and may leaed to false radical treatment. We present a 27 year old man with PSF presenting with microhematuria. Results of clinical, radiological and histopathological examinations and therapy are presented. A. review of the literature data of the to our knowledge 73 cases that have been reported in the literature is given.