[Pathology by the Wall. The autobiography of the Charité chronicler Heinz David].
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History, 20th Century↗
Biomedical subjects
H Nizze
Publications and source records attributed to H Nizze.
Tumour budding as prognostic factor in stage I/II colorectal carcinoma.
AIMS: The term tumour 'budding' has been coined for the detachment of tumour cells from the neoplastic glands of adenocarcinomas and is presumed to be an early step in the metastatic process. A limited number of studies have shown budding to be an adverse prognostic factor. METHODS AND RESULTS: All primary single, non-metachronous TNM stage I/II colorectal carcinomas without neoadjuvant treatment resected in the years 1994-1999 were included (n = 186). Tumour buds were counted in pan-cytokeratin immunostains in a 0.785-mm2 field of vision (250 x). During follow-up 21 patients had distant metastases and 12 patients died of their disease. Budding was determined at 14 and 20.46, median and mean, respectively (range 0-120). A cut-off of 25 was found to be sensitive (0.76) and specific (0.739). Kaplan-Meier survival analysis showed high budding to be a strong adverse prognosticator. By Cox regression, high budding together with venous angioinvasion were independent prognostic factors. CONCLUSIONS: This study confirms the prognostic value of budding in a contemporary series of colorectal carcinomas that by TNM were low risk. Technically easy, rapid and robust to determine, budding quantified in pan-cytokeratin stains significantly aids in the identification of high-risk patients and is recommended for more general use in surgical pathology.
Adult↗
[Paleopathological skeleton findings. Macroscopical and radiographical studies of 364 individuals from a medieval graveyard].
Paleopathological examinations can give an idea of diseases and living conditions in ancient populations. An archaeological collection of 364 late medieval/early modern skeletons from the thirteenth to eighteenth centuries, excavated from a church cemetery in the Rostock town center, was examined palaeopathologically. The type and frequency of certain diseases within this north German urban population are described. The majority of the skeletons were from adults with a remarkably low percentage of children. Skeletal malformations (e.g. gap formations of the spinal column) were not abnormally represented. With the exception of single individuals, metabolic disorders or unusual infectious diseases could not be diagnosed. Degenerative diseases often found at the joints and the spinal column showed substantially lower prevalences in comparison with reference rural populations. Individual cases of benign and rare malignant neoplasms could be documented. Traumatic injuries as well as dental pathological changes were rare. In summary it can be concluded that the individuals buried here belonged to a better social class within the medieval population of Rostock.
Bone and Bones↗
[Rostock--light of the north. Venue of the 88th Annual Meeting of the German Pathology Society on june 2-5 2004].
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Germany↗
[Pathology in Rostock].
The name of Rostock was first mentioned in 1161 by the Danish historian Saxo Grammaticus. As the oldest university in Northern Europe, the Alma mater rostochiensis was inaugurated in 1419 and is proudely called Light of the North ("Leuchte des Nordens"). Its Medical Faculty belonged to the three founding faculties. As elsewhere, the roots of Rostock pathology hark back to anatomy. A Theatrum anatomicum existed since 1790. First lectures on pathology were read by Johann Wilhelm Josephi (1763-1845) who was Head of Anatomy in the so-called Dissection House ("Zergliederungshaus") situated at the Old Market of Rostock. In 1844, anatomy together with its pathology rooms moved into the Garden House ("Gartenhaus") on the university yard. From 1878 to 1930, the Pathology represented one section of the downtown Medical Studies Building. From 1930 up to now, the Pathology Institute is situated in the Strempel Street at the corner of the clinical center. The Rostock Pathology Chair was established in 1865. Since that time, the institute had ten directors. Inter alios, Ernst Schwalbe (1871-1920) was a famous teratologist at the beginning of the 20th century. Walther Fischer (1882-1969) was Head of Institute for 24 years and became well-known as oncopathologist. After World War II, Alexander Bienengräber (1911-1990) reconstructed the institute in all ist compartments to a modern standard. At present, about 40 persons, with eight pathologists among them, represent the staff of the institute. 150 medical students are taught in each semester. Scientific topics concern oral, colorectal and thyroid carcinoma, pancreatitis as well as renal and transplant pathology. Nearly 15,000 histology, 20,000 cytology, and 150 autopsy cases are presently examined per year.
Faculty, Medical↗
[Pancreas transplant pathology: clinicopathologic and experimental findings].
134 pancreas transplantations (113 simultaneous pancreas-kidney, 5 pancreas after kidney, 16 pancreas transplants alone) done in Rostock from VI/95 to III/04 were evaluated in respect to pancreas transplant lesions. Additionally, 36 pancreas specimen of Brown Norway rats experimentally transplanted into diabetic Lewis rats were examined. From 55 out of the 134 pancreas transplant patients, 122 partly repeated pancreas graft specimen examinations were carried out morphologically. The principal lesions in the human pancreas transplants were acute (enzymatic) necrotizing transplant pancreatitis (41 samples), acute (13) and chronic (14) transplant rejection specimen as well as primary or secondary graft thrombosis (12 probes). 23 probes were zero-hour biopsies and 2 showed normal tissue. From 69 out of the 118 pancreas transplant patients with an additional kidney graft, a total of 159 renal transplant probes were examined. They showed the following lesions: acute tubular damage or acute renal failure (23), acute (56) or chronic (22) kidney graft rejection, acute tubular cyclosporine or FK 506 toxicity (53), and histologically normal graft tissue (8 cases). As in other grafted organs, the changes occurring in the transplanted pancreas consist of varying lesions related and/or not related to pancreas transplant rejection. A concise classification and a reproduceable grading schedule are suggested for diagnostic, differential diagnostic, therapeutic, and prognostic purposes. Pancreatic rejection lesions can be classified according to a proposed Rostock '04 working classification of pancreas allograft rejection into three grades (I: mild, II: moderate, III: severe) both for acute and chronic pancreas rejection. There was no direct correlation of the findings in 21 patients with simultaneously studied pancreas and renal transplant biopsies. In contrast to renal grafts, pancreatic rejection signs were often superimposed by acute transplantation pancreatitis with or without secondary graft thrombosis, nonenzymatic necroses or infection. Experimental acute pancreas transplant rejection in rats showed quite similar findings to human grafts and was also graded into three different acute rejection stages.
Animals↗
[Interlaboratory trial 2000 " Immunohistochemistry" of the German Society for Pathology and the Professional Association of German Pathologists].
Early in 2000 an interlaboratory trial on immunohistochemistry was held in Germany in which 172 pathologists took part. Each pathologist received one H&E stained and five unstained slides of five different tumors to reach a diagnosis based on immunohistochemical stains. Additionally, the diagnosis-independent staining quality was assessed by using a multi-tissue block. Altogether, 828 diagnoses were made, among which 57% (468) were correct. The individual steps of immunohistochemistry (tentative morphological diagnosis, choice of primary antibodies, technical staining quality, conclusions from the diagnosis and rendering a final diagnosis) were assessed independently. Although each of these steps was correlated to the correct final diagnosis, in the multivariate analysis only the tentative diagnosis, choice of primary antibodies and the conclusions drawn from individual stains were independent factors to reach the correct final diagnosis. In the diagnostic part of the interlaboratory trial, the technical quality of the immunostaining was not an independent variable to reach a correct diagnosis. In contrast, the results of the multi-tissue block proved that the immunohistochemical staining quality has to be standardized to reach reproducible results in defining the estrogen receptor expression as a basis for therapeutic decisions.
Coloring Agents↗
[Glomerular diseases in renal biopsy. Correlation of clinical syndromes with histological types].
Renal biopsies studied by light and electron microscopy as well as by immunohistochemistry seem to be continually necessary for an adequate typing and therapy of glomerulonephritis (GN) and other glomerular diseases. Basing on 653 renal biopsies examined in Rostock from 1990 to 1999, the morphological classification in a total of 585 cases with glomerular diseases is presented in comparison to their clinical syndromes according to the WHO classification. A nephrotic syndrome was most frequent and clinically reported in 258 of the 585 biopsy cases with glomerular diseases (44%). It was seen in 77 of the 87 cases with minimal change nephropathy (55%), in 46 of the 74 cases with focal segmental glomerulosclerosis (62%), and in 19 of the 24 diffuse membranous GN cases (79%). The majority of the varying histological subtypes of diffuse GN was not combined with a specific clinical syndrome except of diffuse crescentic GN presenting with a rapidly progressive nephritic syndrome in 14 of 16 cases (88%). IgA nephropathy was the most often diagnosed entity of glomerular diseases found in 122 of the 502 cases with primary or secondary GN (24%). It is obvious that a given morphological GN type can but must not be combined with a specific clinical GN syndrome, so that the clinical importance of renal biopsy is stressed.
Anti-Glomerular Basement Membrane Disease↗
[Primary renal manifestation in malignant lymphomas and leukemia].
Primary manifestation of malignant lymphoma and/or leukaemia rarely occurs in the kidney. It can be the cause of a hitherto unexplained acute renal failure or it is incidentally detected as shown in the three cases under report.1.A 68-year-old man was operated on because of a symptomatic tumour in his right kidney. At nephrectomy, a conventional (clear cell) renal cell carcinoma was found simultaneously with an occult mantle cell lymphoma infiltrating the adjacent renal and extrarenal tissue. Clinical follow-up uncovered nodal and bone marrow involvement, so that a primary renal manifestation of mantle cell lymphoma was apparent.2.A 69-year-old man with suspected vertebral metastasis underwent partial renal resection because of a mass in his left kidney. Histologically and immunohistochemically, the renal infiltration was diagnosed as a precursor B-lymphoblastic lymphoma. After chemotherapy and irradiation, leukaemic blood cell counts with 50% lymphoblasts proved a primary renal manifestation of precursor B-lymphoblastic leukaemia/lymphoma.3.A 13-year-old boy presented clinically with renal failure, enlarged kidneys, and normal urinalysis. Renal biopsy showed a diffuse interstitial infiltration with atypical T-lymphoblasts compressing tubules and surrounding preserved glomeruli. Subsequent clinical bone marrow smears presented 60% T-lymphoblasts, so that the final diagnosis of a primary renal manifestation of acute T-lymphoblastic leukaemia of mature thymic cortex type was made. Immediate chemotherapy resulted in total recovery of renal function and bone marrow findings.
Adenocarcinoma, Clear Cell↗
[Hantavirus-induced acute renal failure. A case report].
A non-ischemic acute renal failure may indicate a hantavirus nephropathy, so that appropriate serological examinations should be done. A 19-year-old man had acutely fallen ill with fever, rhinitis, and arthralgia. Clinically, he presented with a polyuric renal failure as well as hypertension, proteinuria, erythro- and leucocyturia. Serologically, IgG- and IgM-hantavirus antibodies were found against the Central European variant of hantavirus Dobrava. At renal biopsy, tubular epithelial swelling, vacuolization, and necrosis as well as interstitial hemorrhages were seen. Electron microscopically, virion particles with a gridlike surface structure as well as with the shape and dimension evident of hantaviruses could be detected in the nucleus and cytoplasm of renal tubular cells. After a clinical course of 3 weeks, the patient was free of complaints and cured with a restitutio ad integrum.
Acute Kidney Injury↗
Microvessel densities and microvascular architecture in colorectal carcinomas and their liver metastases: significant correlation of high microvessel densities with better survival.
AIMS: Microvessel densities in cancers have been shown to be a prognostic factor for some types of cancer. For colorectal cancer, however, the situation is far from clear. METHODS: A consecutive series of 173 colorectal carcinomas was investigated, and to these were added 55 liver metastases originating from colorectal cancer. Microvessels were counted in hotspots (factor VIII immunostaining, 0.74 mm2). The capillary architecture was scored according to the degree of order and envelopment of the neoplastic glands. Endothelial proliferation was determined by factor VIII/Ki67 double labelling. RESULTS: Mean microvessel densities were 51.8 for colorectal carcinomas (range 8-140) and 31.9 for liver metastases (range 3-101). Stratification according to stage, depth of infiltration and nodal involvement showed a significant inverse relation with increase. Mean microvessel densities in primaries were significantly higher than in metastases. Kaplan-Meier analysis showed a significantly higher cancer-specific survival for high microvessel densities (median as cut-off) and for a more ordered microvascular architecture. Endothelial proliferation in carcinomas was significantly higher than in normal mucosa. CONCLUSIONS: Contrary to other types of cancer, for colorectal cancer high microvessel densities confer good rather than poor prognosis. We hypothesize that neoangiogenesis, though extant in colorectal cancer, is not rate-limiting in the metastatic cascade.
Adenocarcinoma↗
Effect of nitric oxide in ischemia/reperfusion of the pancreas.
BACKGROUND: Ischemia/reperfusion injury, and thus graft pancreatitis, remains a major problem in pancreas transplantation. Contradictory results about the role of nitric oxide (NO) in pancreatic ischemia/reperfusion have been reported; however, in none of the reports has a detailed comparison between inhibition of NO synthase and NO supplementation been carried out. METHODS: Vascular isolation of the pancreatic tail was performed in landrace pigs. After splenectomy catheters placed in the distal part of the splenic vessels allowed collection of the venous effluent and perfusion of the pancreatic tail. Three hours of complete warm ischemia was followed by 6 h of reperfusion. The effect of the NO donor sodium nitroprusside (SNP) and L-arginine was compared to a control group and NO synthase inhibition with L-NAME. RESULTS: Lipase in the venous effluent of the pancreas was significantly decreased in the SNP and the L-arginine groups. Vascular resistance was markedly elevated in the L-NAME group and reduced in the NO donor groups. Tissue pO2 after reperfusion was only significantly elevated in the SNP group. Granulocyte infiltration and also overall histological tissue injury were most severe in the control group followed by the L-NAME group, the SNP group, and the L-ARG group. CONCLUSION: The data show that supplementation of nitric oxide is clearly protective in pancreatic ischemia/reperfusion. However, inhibition of NO synthesis does not lead to an equally clear aggravation of tissue injury.
Acute Disease↗
[Primary aortoduodenal fistula as a late complication of para-aortic radiation therapy. A case report].
Primary aortoenteric fistulae (AEFs) are rare vascular entities. More than 75% of primary AEFs involve the duodenum, with the overwhelming majority located in the third or fourth portion. Atherosclerosis, leading to formation of an aortic aneurysm, remains the most common etiology, accounting for more than 3/4 of the cases reported. Primary aortoenteric fistulae following radiotherapy are rare. The case of a 49-year-old man with aortoduodenal fistula 22 years after para-aortic radiation is presented. In November 1997, the patient suddenly developed hematemesis and melena. Endoscopy suggested the presence of an ulcus but no definitive bleeding source could be seen. Bleeding stopped spontaneously. Six hours later he developed massive hematemesis and was transferred to our department. An emergency operation was performed. We found an aorto-duodenal fistula in the third portion of the duodenum without an aortic aneurysm. We directly sutured the aortic wall laceration and resected the third and fourth part of the duodenum. Histology revealed typical signs of radiation damage. The patient is alive and well 2 years after surgery. To our knowledge, this is the sixth case of a primary aorto-duodenal fistula following radiotherapy ever to be reported in world literature.
Aorta↗
Immunoadsorption of sensitized kidney transplant candidates immediately prior to surgery.
Patients with anti-human leucocyte antigen (HLA) antibodies from previous transplantation, blood transfusion are highly sensitized and at risk to hyperacute renal graft loss. As these antibodies are identified to be of pathogenic importance, an effective removal may allow successful transplantation. Six 'high risk patients' [panel-reactive antibodies (PRA) >30% or retransplanted patients with an acutely rejected first graft within 6 months from surgery] were treated by protein A immunoadsorption (IA) immediately prior to transplantation. We treated the calculated plasma volume one to three times prior to surgery: mean 4600 mL (range 2100-10 200 mL). After transplantation we repeated the sessions according to antibody (Ab) recurrence, graft function and signs of rejection. The panel reactive Ab were reduced from mean 65% pre-IA (range 35-85) to lowest 15% (range 0-55). After the course they reappeared to 30% (range 0-90). Five of the six patients had no clinical signs of vascular rejection. At a follow-up of mean 54 months (+/-14) four grafts still function with a mean serum creatinine of 172 micromol/L (+/-57). Protein A IA is a safe and effective adjunct in the treatment of highly sensitized patients awaiting renal transplantation. The treatment immediately prior to operation can prevent hyperacute rejection and increases the graft survival in these patients.
Adult↗
Quality assurance in immunohistochemistry: results of an interlaboratory trial involving 172 pathologists.
The practicability of quality assurance in immunohistochemistry and its integration into the diagnostic process were both tested in this Germany-wide interlaboratory trial. One hundred seventy-two pathologists received one hematoxylin and eosin and five unstained slides from five cases; all cases were selected by a panel because immunohistochemistry was required for their final diagnosis. Participants rendered a morphologic diagnosis and then substantiated it immunohistochemically. Stained slides and evaluation sheets were reviewed by the panel, and the diagnostic process was analyzed in individual steps: morphologic diagnosis, selection of antibodies, staining quality, interpretation of stained slides, conclusions, and final diagnosis. Diagnosis-independent immunohistochemical performance was tested using a multisample tissue block (30 samples) that was stained and evaluated for six common antigens. For individual cases, corresponding to their difficulty, 21-89% of the final diagnoses (altogether 57% from 828 diagnoses) were correct. In a statistical analysis, the tentative diagnosis, the interpretation of stains and conclusions drawn from immunohistochemistry, were independent factors in reaching the diagnosis. Sensitivity to detect estrogen receptors on the multisample tissue block was only 48%. However, 24% of the stains were interpreted as falsely negative. The low staining sensitivity was not correlated to the number of correct diagnoses. The major problem of applying immunohistochemistry in surgical pathology appears to be its integration into the diagnostic process and not the staining quality. Both future quality control projects and training will have to regard these integrative requirements. Multisample tissue blocks provide a promising tool to standardize quantitative immunohistochemical parameters, such as receptor or proliferation scores.
Coloring Agents↗
Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma.
Pancreatic cancer can seldom be resected, and chemotherapy has only a limited effect on survival or tumour load. We did a phase I/II trial in 14 patients with pancreatic cancer to assess the safety of local activation of low-dose ifosfamide. We encapsulated genetically modified allogeneic cells, which expressed a cytochrome P450 enzyme, in cellulose sulphate and delivered them by supraselective angiography to the tumour vasculature. These cells locally activated systemically administered ifosfamide. The tumours of four patients regressed after treatment, and those of the other ten individuals who completed the study remained stable. Median survival was doubled in the treatment group by comparison with historic controls, and 1-year survival rate was three times better. Further studies of this cell-therapy-based treatment combined with chemotherapy for inoperable pancreatic cancer are warranted.
Adenocarcinoma↗
Transforming growth factor-beta1 induces desmoplasia in an experimental model of human pancreatic carcinoma.
Proliferation of fibrotic tissue (desmoplasia) is one of the hallmarks of several epithelial tumors including pancreatic adenocarcinoma. This tissue reaction may be deleterious or advantageous to the host or tumor. In a systematic analysis, we identified two growth factors expressed by human pancreatic carcinoma cells that are positively correlated with the ability to induce fibroblast proliferation both in vitro and in vivo, i.e., transforming growth factor (TGF)-beta1 and fibroblast growth factor-2. Here we demonstrate that the overexpression of TGF-beta1 induced up-regulation of matrix proteins and growth factors in the TGFbeta1-transfected pancreatic tumor cells. Furthermore, transfection of PANC-1 cells induces the same change in fibroblasts in either cocultivation experiments or when they are grown in conditioned medium from TGF-beta1-transfected PANC-1 cells. TGF-beta1-transfected pancreatic tumor cells induced a rich stroma after orthotopical transplantation in the nude mouse pancreas. The transfer of a single growth factor, TGF-beta1, conveys the ability to induce a fibroblast response similar to that seen in desmoplasia in human pancreatic adenocarcinoma. This effect cannot only be attributed to direct effects of TGF-beta1 but also results from the up-regulation of several other factors including collagen type I, connective tissue growth factor, and platelet-derived growth factor.
Animals↗
[Pathology for the 21st century. Invitation to the 85th Congress of the German Society for Pathology in Munster, 6-9 June 2001].
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Germany↗