Laparoscopic renal surgery.

Renal surgery, radical nephrectomy in particular, was historically the first application of laparoscopic techniques in urology. Since then, laparoscopy has been constantly evolving to claim its position in the surgical armamentarium of the urologist for the treatment of both malignant and benign diseases of the kidney and upper urinary tract. Over the years of increasing surgical experience and exposure, along with the evolution in the techniques and instruments used, laparoscopy has emerged as an equally effective and even more attractive alternative to open surgery for certain indications. The currently available load of literature is able to prove beyond any doubt the oncologic efficacy and minimal morbidity of laparoscopy for the treatment of renal masses in the form of radical or partial laparoscopic nephrectomy and nephroureterectomy. On the other hand, one can claim that laparoscopy is not far from replacing open surgery for the management of benign conditions such as ureteropelvic junction obstruction and donor nephrectomy. This review on laparoscopic renal surgery will discuss the major applications, indications, techniques and outcomes of laparoscopy in the contemporary management of benign and malignant renal diseases while focusing on its benefits and drawbacks compared to open surgery.

[Diagnostic and therapeutic procedures in actinomycosis of the liver--a case report]. / Kasuistischer Beitrag zur Diagnostik und Therapie der Leberaktinomykose.

Actinomycosis is a rare disease. Clinical symptoms and diagnostic imaging results need to be differentiated from those of malignancies and abscesses. We report the case of a 51-year-old woman who presented with nocturnal sweating, weight loss, fever, and abdominal pains. Ultrasound and MRI showed a mass in the liver that was diagnosed as actinomycosis by fine needle -biopsy. Antibiotic therapy led to an initial de-crease of both the complaints and the size of the mass, but was followed by progressing inflammation and deterioration of the patient's general condition. Surgical intervention and resection of the liver lesion led to a near full recovery. Aetiology, symptoms, diagnostic measures and therapy are discussed in the context of the presented clinical case.

[Pseudomalignant primary renal actinomycosis after ureterosigmoidostomy. A case report]. / Nierenaktinomykose nach Ureterosigmoidostomie. Ein Fallbericht.

Actinomycosis is a chronic infectious disease caused by a gram-positive anaerobe. The bacterial disease is known to predominantly affect the oropharyngeal mucosa and soft tissues as well as the gastrointestinal tract. However, renal involvement by actinomycosis is exceedingly rare. Thus, renal actinomycosis is usually diagnosed by means of histopathological assessment of nephrectomy specimens because affected patients seek medical care due to (peri-) renal mass lesion clinically mimicking cancer. To best of our knowledge, we present the first case worldwide reporting on a 65-year-old man diagnosed with renal actinomycosis following ureterosigmoidostomy in whom nephrectomy was performed due the clinical suspicion of renal cancer (stage cT4). Subsequently, calculated antibiotic therapeutic regimens were initiated after the diagnosis was suspected by the pathologist. During the entire postsurgical follow-up comprising a total of 6 months, the patient did not experience any local or systemic recurrence. In summary, detailed information concerning the etiology, the clinical symptoms as well as diagnostic and therapeutic options are discussed in our case report.

[Coincidence of testicular germ cell tumor and sarcoidosis: A diagnostic challenge]. / Testikulärer Keimzelltumor und Sarkoidose: Eine diagnostische Herausforderung.

Several case reports and small case series have described a total of 66 patients with sarcoidosis and testicular cancer so far. This report describes three additional cases. We highlight the association of sarcoidosis and testicular cancer and comment on the potential impact of this connection on the interpretation of the radiological and pathological findings in suspected cancer relapse. Sarcoidosis, a condition that can be combined with testicular cancer, should always be considered in the differential diagnosis.

Dissemination of a Sjögren's syndrome-associated extranodal marginal-zone B cell lymphoma: circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements.

OBJECTIVE: Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions. METHODS: Histopathologic and Ig heavy- and light-chain variable-region gene (V(H/L)) analyses were performed in sequential tissue samples from a patient with primary Sjögren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL. RESULTS: This MZL expressed a CD20+,CD27+,sIgM/kappa+,IgD-,CD5-,CD10-,Bcl-6-,CD23-,p53-,p21-,MDM2- phenotype and mutated V(H)1-69/D2-21/J(H)4alpha-V(kappa)A27/J(kappa)2 Ig rearrangements. Notably, circulating lymphoma cells from the parotid glands occurred transiently in the patient's blood, as detected by single-cell polymerase chain reaction. In addition, 2 minor B cell clones (clones 2 and 3, with V(H)3-07/D3-22/J(H)3b-V(lambda)3L/J(lambda)2/3 and V(H)3-64/D3-03/J(H)2-V(kappa)A19/J(kappa)2 rearrangements, respectively) were also detected in the parotid glands and blood, and 1 of these (clone 2) was also detected in the lymph nodes. Ig V(H/L) analyses revealed ongoing (antigen-driven) mutations of the glandular lymphoma rearrangements, but an invariant mutation pattern of their nodal counterparts. CONCLUSION: These data indicate coexpansion and transient (re)circulation of the lymphoma clone and 2 additional glandular B cell clones in a primary SS-associated extranodal MZL. Combined histologic and molecular features of the nodal lymphoma subclone reflect a process of "follicular colonization" that eventually froze the mutation machinery after accumulation of additional (antigen-driven) Ig V(H/L) mutations.

Morphology of the suburethral pubocervical fascia in women with stress urinary incontinence: a comparison of histologic and MRI findings.

To correlate MRI with histologic findings of the suburethral pubocervical fascia in women with urodynamic stress incontinence. Thirty-one women with urodynamically proven stress urinary incontinence without relevant prolapse underwent preoperative MRI. Tissue specimens obtained from the pubocervical fascia were examined immunohistochemically (types I and III collagen, smooth muscle actin) and the results compared with the MRI findings. MRI demonstrated an intact pubocervical fascia in 61.3% of the cases and a fascial defect in 38.7%. A fascial defect demonstrated by MRI was associated with a decrease in actin (P<0.09) and an increase in collagen III (P<0.01) compared to an intact fascia. In women with stress urinary incontinence, smooth muscle actin in the pubocervical fascia is decreased, changed in structure, and replaced by type III collagen. MRI allows evaluation of the pubocervical fascia and its morphologic changes.

[Health, growing performance and meat quality of pigs in indoor and outdoor housing--a controlled field trial]. / Gesundheit, Mastleistung und Fleischqualität von Schweinen in der Stall- und Freilandhaltung--ein kontrollierter Feldversuch.

The purpose of the study was to compare indoor and outdoor housing of pigs and their influence on animal health, growing performance and meat quality in a controlled field trial: 29 litters (252 piglets) from indoor and 22 litters (221 piglets) from outdoor were separated at weaning. One half of each litter changed to the opposite housing resulting finally in 4 types of housing: Continuous outdoor or indoor raising and combined outdoor-indoor or indoor-outdoor raising. Pigs in continuous resp. predominant outdoor housing showed lower morbidity and mortality during all raising periods, more active behaviour, higher daily weight gain in weaned pigs and in fattening pigs, but higher feed consumption as compared to indoor housed pigs. However, feed conversion did not differ significantly. Due to climatic influences differences in morbidity were partly more significant in summer litters (intestinal infections) or in winter litters (lung infections). Outdoor pigs raised in summer resulted less often in meat classification E (lean meat percentage > 55%), however, meat quality, estimated by pH-measures did not differ significantly. We conclude from our findings that outdoor housing of pigs from birth to slaughtering may be a serious alternative to predominant indoor keeping with regard to general welfare and growing performance.

[Solitary renal cell carcinoma metastasis to the thyroid gland--a paradigm of metastasectomy?]. / Die solitäre Nierenzellkarzinommetastase in der Schilddrüse. Ein Paradigma der Metastasenchirurgie?

We investigated the usefulness of thyroidectomy for solitary metastases from renal cell carcinomas in ten patients. In the absence of postoperative morbidity and mortality, a mean survival time of 3.4 years was observed. Subsequently, four patients developed intracerebral metastases. Swelling of the neck and the discovery of a nodule in the thyroid of patients who have undergone nephrectomy for renal cell carcinoma should raise suspicion of a metastasis, possibly after a long latency period. With the aid of modern immunohistochemical methods, renal cell carcinoma metastasis can now be identified unequivocally, with differentiation from a primary follicular carcinoma of the thyroid rendered possible by a combination of TTF-1, thyroglobulin, and CD 10. In the event of a solitary lesion with no extrathyroidal tumour manifestation, an R0 resection of the metastasis should always be attempted. If tumour dissemination has occurred, palliative measures and endoscopic intervention (e.g. placement of an endotracheal stent) with the aim of improving quality of life by preventing obstruction of the airways are justified.

Comparison of immunoglobulin heavy chain rearrangements between peripheral and glandular B cells in a patient with primary Sjögren's syndrome.

Myoepithelial sialadenitis (MESA) of the major salivary glands is a characteristic feature of primary Sjögren's syndrome (pSS). To delineate systemic and organ-specific influences on B cells in a patient with pSS and benign MESA, individual B cells were simultaneously obtained from the peripheral blood and inflamed parotid gland. Immunoglobulin variable heavy chain (VH) rearrangements in single sorted CD19+ B cells were subsequently amplified, sequenced and analysed. Despite the presence of two clonal expansions using VH1-08 and VH2-70 segments, respectively, the majority of glandular B cells were polyclonal, resembling the VH gene usage and mutational pattern of the corresponding blood population. However, striking differences were observed in the proportion of cells expressing mutated VH rearrangements (blood, 28.9% versus parotid, 80.4%; P < 0.0001). Moreover, the glandular productive VH rearrangements differed significantly from their blood counterparts by a higher mutational frequency (P < 0.0001), shorter CDR3 lengths (P = 0.001) and a less frequent usage of JH6 (P = 0.0292), indicating an accumulation of memory B cells in the inflamed parotid. Thus, both preferential influx/homing of memory B cells and local proliferation may contribute to the pattern of benign MESA in pSS. Notably, one of the glandular clonal rearrangements (using VH1-08) was also detected in the patient's peripheral repertoire.

[Immunohistochemical diagnosis in cancer metastasis of unknown primary tumor]. / Immunhistochemische Diagnostik bei Karzinommetastasen mit unbekanntem Primärtumor.

Immunohistochemical studies on metastatic carcinomas of unknown primary site are cost-effective and often allow a specific identification of the tumour origin, especially if the metastases are adenocarcinomas by light microscopy. Commercially available site-specific markers include prostate-specific antigen, thyroglobulin, thyroid transcription factor-1, uroplakin III, GCDFP-15, oestrogen and progesterone receptors, alpha-fetoprotein, the A103 monoclonal antibody against MART-1, cytokeratins 7 and 20, cytokeratins of basal cell type, p63, carcinoembryonic antigen, CA125, EMA, vimentin, HepPar-1, WT-1 and S100 protein. However, immunostaining with most of these markers does not show an absolute specificity for a certain primary site. For this reason, histopathologists interpretating staining results with these markers should take the available clinical data and the histological features of the metastatic carcinoma into consideration. These data are necessary to estimate the relative a priori probability of possible carcinomas. Based on Bayes' theorem, the a priori probability can then be used to calculate the diagnostically relevant predictive values for immunostaining results with the chosen markers.

Relationship between bone marrow angiogenesis and plasma cell infiltration and serum beta2-microglobulin levels in patients with multiple myeloma.

There is growing evidence that angiogenesis is important not only in solid tumors but also in hematological malignancies. Recently, we found that bone marrow angiogenesis is a prognostic factor for disease-related survival in patients with multiple myeloma. In this report, we addressed the question of whether the microvessel density in bone marrow biopsies is correlated to other myeloma parameters, e.g., serum beta2-microglobulin (beta2-MG) and plasma cell infiltration in the bone marrow. In 22 multiple myeloma patients, immunohistochemical, CD34-stained, paraffin-embedded bone marrow biopsies before and after chemotherapy were studied. Microvessels were counted in 400x magnification, and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). Pretreatment bone marrow MVD (median: 44, range: 11-175 vessels/mm2) correlated significantly with the bone marrow plasma cell infiltration (median: 30%, range: 5-90%, r = 0.642, P=0.001) and beta2-MG (median: 2.74, range: 1.4-26.1 mg/l, r = 0.749, P < 0.0005). In contrast, there was no correlation between posttreatment MVD and plasma cell infiltration or beta2-MG (median: MVD 31, range: 0-221 vessels/mm2, median plasma cell infiltration: 15%, range: 5-80%, r = 0.229, P = 0.306 and median beta2-MG: 2.65, range: 1-27.6 mg/l, r = -0.042, P = 0.853). These findings show that the strong correlations between bone marrow MVD and plasma cell infiltration as well as serum beta2-MG levels disappear after chemotherapy. The underlying mechanisms need further investigations.

Decrease of bone marrow angiogenesis in myeloma patients achieving a remission after chemotherapy.

The impact of angiogenesis is well known for the growth and viability of solid tumors. Fewer studies have been published relating angiogenesis to clinical or pathological parameters in hematological malignancies. In this report, we have estimated the bone marrow microvessel density (MVD) before and after conventional-dose or high-dose chemotherapy with autologous stem cell transplantation. Immunohistochemical CD34-stained paraffin-embedded bone marrow biopsies of 21 patients with stage III multiple myeloma were studied. Microvessels were counted at 400x magnification, and the mean number of vessels per area in each sample was noted as the MVD. The median MVD of all patients was 53.1 vessels/mm2 (range 15.5-174.7 vessels/mm2) before treatment and 29.3 vessels/mm2 (range 0-221.1 vessels/mm2) after chemotherapy. The post-treatment MVD in the two groups of patients with and without remission was significantly different (p=0.001), whereas the pretreatment MVD was not. Responders but not nonresponders showed a significant decrease of MVD after therapy in comparison to their pretreatment levels. The progression-free survival in patients who achieved a reduction in MVD after chemotherapy was significantly longer than in patients without a decrease in MVD (P=0.006). Furthermore, we compared the MVD of patients after achievement of a remission to MVD of 15 untreated stage I myeloma patients. The MVD of patients in remission was not statistically different from the MVD in stage I myeloma. These results underscore the impact of angiogenesis in myeloma and give the first report that effective chemotherapy is accompanied by a significant decrease in bone marrow angiogenesis in this disease.

Overexpression of c-erbB2 protein correlates with disease-stage and chromosomal gain at the c-erbB2 locus in non-small cell lung cancer.

Overexpression of the c-erbB2 protein is observed in a variety of malignancies including non-small cell lung cancer (NSCLC). We aimed to determine the rate of c-erbB2-overexpression in our tumour collection and to clarify its correlation with the chromosomal status at the c-erbB2 locus 17q21 in NSCLC. Eighty-nine NSCLC were analysed immunohistochemically using a polyclonal c-erbB2 antibody (DAKO). The staining was scored according to the guidelines of the Clinical Trial Assay recommendations (0-3+). Of these, 44 cases were also analysed by comparative genomic hybridisation (CGH). Overexpression was observed in 37% of the cases (score>1) which was associated with higher disease stages and a positive nodal status in adenocarcinomas. Chromosomal gains at 17q21 were clearly correlated with overexpression of the gene (P=0.009). In addition, there was a highly significant correlation between the c-erbB2 expression comparing the whole section immunostaining analysis and a 127 lung tumour tissue array which included 74 of the 89 cases that were analysed by the classical procedure. We conclude that c-erbB2 is a marker of tumour progression in NSCLC which can be observed on protein level and reflects chromosomal alterations at 17q21.

Achievement of complete remission in refractory Hodgkin's disease with prolonged infusion of gemcitabine.

Although, in recent decades effective chemotherapy regimens have been developed for the treatment of Hodgkin's disease, the prognosis of patients who experience disease progression is still very poor. New treatment approaches are urgently required to salvage such patients. In a patient with Hodgkin's disease who failed to achieve complete remission with the escalated BEACOPP protocol, progression with bone marrow infiltration and B symptoms developed despite further treatment. Subsequently, gemcitabine was administered in a novel schedule as a four-hour infusion of 250 mg/m2 on days 1, 8, and 15, every four weeks. After the first cycle, the dose was reduced to 200 mg/m2 because of grade 3 neutropenia. The condition of the patient improved after the second cycle and no toxicity was observed during cycles 3-6. Complete remission was achieved. Two years after the end of gemcitabine therapy, the patient is in good clinical condition and in continuous complete remission without further treatment. This is the first report of the prolonged infusion of gemcitabine as a salvage therapy in Hodgkin's disease.

Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas.

To facilitate the differential diagnosis of poorly differentiated metastatic carcinomas of unknown primary site, we evaluated p63 and cytokeratin (CK) 5/6 as immunohistochemical markers for squamous cell carcinomas. The study cases were as follows: squamous cell carcinoma of the lungs, head/neck, esophagus, cervix uteri, or anal canal, 73; non-squamous cell carcinomas of various primary sites, 141; and urothelial carcinoma, 20. We also tested 14 malignant mesotheliomas. Immunoreactivity for p63 was as follows: squamous cell carcinomas, 59 (81%); urothelial carcinoma, 14 (70%), most often with diffuse staining patterns; non-squamous cell carcinomas, 20 (14.2%), resulting in a specificity of 0.86 of p63 for squamous cell carcinomas. Coexpression of p63 and CK5/6 had a sensitivity of 0.77 and a specificity of 0.96 for squamous cell carcinomas. Increasing the minimal criterion of positive immunostaining for both markers to more than 50% of immunoreactive tumor cells resulted in a specificity of 0.99, although the sensitivity diminished to 0.66. All malignant mesotheliomas were negative for p63. Our data suggest that positive immunostaining for both p63 and CK5/6 in poorly differentiated metastatic carcinomas is highly predictive of a primary tumor of squamous epithelial origin.

Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma.

The importance of neoangiogenesis for the progressive growth and viability of solid tumors is well established. Recently, there has been growing evidence that angiogenesis might also be important in hematological malignancies, but only few data are available. In this report, we have studied the impact of bone marrow microvessel density and survival in patients with multiple myeloma (MM). Immunohistochemical CD34 stained paraffin-embedded bone marrow biopsies of 44 patients with newly diagnosed MM were studied. Microvessels were counted in 400 x magnification and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). The median MVD was 48 vessels/mm2, the range was 0-125 vessels/mm2. Using a cut-off value of the median MVD in the Kaplan-Meier analysis, the median survival was 22.2 months in the group with the higher MVD and was not reached in the group with the lower MVD (P< 0.01). In a multivariate Cox regression analysis, using previously identified prognostic factors beta2-microglobulin, C-reactive protein (CRP), and age, MVD remained significant as a prognostic factor (P< 0.03).

Vascular endothelial growth factor and its correlation with angiogenesis and p53 expression in prostate cancer.

BACKGROUND: Previously it was demonstrated that in prostate tumors, angiogenesis measured as microvessel density (MVD) is associated with tumor stage as well as WHO grade and is an independent predictor of clinical outcome. Vascular endothelial growth factor (VEGF) is a major inducer of angiogenesis. There is some evidence that P53 mutations cause overexpression of VEGF. We studied VEGF expression, p53 overexpression, and P53 mutations in prostate cancer (PCA) to investigate the role of VEGF as an angiogenic marker and the possible deregulation of VEGF as a result of P53 mutations in PCA. METHODS: Immunohistochemical staining with a polyclonal VEGF antibody was performed in 55 paraffin-embedded PCA, in which MVD had previously been determined, as well as in 5 prostatic adenomas (PA) and 20 adjacent normal prostate tissues. In addition, 37 PCA and 5 PAs were examined for p53 expression by immunohistochemistry. Temperature gradient gel electrophoresis (TGGE) was performed in 13 of these PCA to screen for P53 mutations. VEGF expression, p53 expression, and mutations were then correlated with tumor stage, grade, MVD, and clinical outcome. RESULTS: While PA and normal prostate tissue generally showed no or only low VEGF expression, there was a significant increase in VEGF expression with tumor stage, grade, and MVD in PCA. During clinical follow-up (mean, 31.9 months), 9 of 55 patients had tumor progression. Significant differences in VEGF expression were found between patients with tumor progression and those without (P = 0.0004). Of the 37 PCA evaluated for p53 expression, 12 exhibited p53 overexpression. TGGE revealed P53 mutations in 3 of 13 PCA. However, there was no correlation between VEGF expression, p53 overexpression, and P53 mutation, respectively. CONCLUSIONS: VEGF seems to be an important, clinically relevant inducer of angiogenesis in PCA. VEGF expression was shown to correlate positively with tumor stage, grade, MVD, and clinical outcome. However, regulation of VEGF in PCA appears to be independent of p53 expression.

Chromosomal imbalances in brain metastases of solid tumors.

Metastases account for approximately 50% of the malignant tumors in the brain. In order to identify structural alterations that are associated with tumor dissemination into the central nervous system we used Comparative Genomic Hybridization (CGH) to investigate 42 brain metastases and 3 primary tumors of 40 patients. The metastases originated from lung cancer (14 cases), melanomas (7), carcinomas of breast (5), colon (5), kidney (5), adrenal gland (1) and thyroid (1). In addition, tumors of initially unknown primaries were assessed in 3 cases. The highest incidence of DNA gains were observed for the chromosomal regions 1q23, 8q24, 17q24-q25, 20q13 (>80% of cases) followed by the gain on 7p12 (77%). DNA losses were slightly less frequent with 4q22, 4q26, 5q21, 9p21 being affected in at least 70% of the cases followed by deletions at 17p12, 4q32q34, 10q21, 10q23-q24 and 18q21-q22 in 67.5% of cases. Two unusual narrow regional peaks were observed for the gain on 17q24-q25 and loss on 17p12. The incidence at individual loci can be viewed at our CGH online tumor database at http:// amba.charite.de/cgh/. The metastases of each tumor type showed a recurrent pattern of changes. In those cases with primary tumor and metastases available, the CGH pattern exhibited a high degree of conformity. In conclusion, our data suggests that specific genetic lesions are associated with tumor dissemination into the nervous system and that CGH analysis may be a useful supplementary tool for classification of metastases with unknown origin.

An unusual case of leukemic non-Hodgkin's lymphoma with blastic transformation.

We report on a patient who was diagnosed as having B-cell chronic lymphocytic leukemia (CLL) with atypical morphology. Flow cytometry disclosed CD5, CD19, and CD23 positivity, an immunophenotype seen mostly in B-CLL. Histology of the spleen and bone marrow suggested a diagnosis of small lymphocytic lymphoma. Upon blastic transformation, only 3 years after the diagnosis had been made, unusual clinical and laboratory features emerged. Lymphoid blasts appeared in the peripheral blood, and the patient developed nodular infiltrates consisting of these blasts at recent venous puncture sites. The patient did not respond to chemotherapy and died. The lymphoid blasts in the peripheral blood were CD5-, CD19+, and CD23+ and harbored t(11;14) (q13;q32) and t(11;21)(p11;q21) translocations. To account for the possibility of two independent lymphoid malignancies, molecular genetic analyses were performed on samples from the spleen, bone marrow and a lymph node with the large-cell lymphoma, which showed identical clones in these tissues. This unusual case supports the idea that in leukemic non-Hodgkin's lymphoma, in addition to morphology, an accurate diagnostic workup requires immunophenotypic, cytogenetic, and molecular studies.