High prevalence of pseudotumors in patients with a Birmingham Hip Resurfacing prosthesis: a prospective cohort study of one hundred and twenty-nine patients.

BACKGROUND: Recently, concern has emerged about pseudotumors (lesions that are neither malignant nor infective in the soft tissues surrounding total hip arthroplasty components) after hip arthroplasties with metal-on-metal bearings. Patients treated in our hospital for degenerative arthritis of the hip with a Birmingham Hip Resurfacing (BHR) prosthesis were invited to return for follow-up evaluation. The prevalence and clinical relevance of pseudotumors were investigated. Risk factors for pseudotumor formation were sought. METHODS: A single-center cross-sectional prospective cohort study was conducted and included all patients who received a BHR from 2005 to 2010 in Martini Hospital, Groningen, The Netherlands. Data were collected on patient and surgical characteristics, clinical hip outcome scores (Harris hip score and Oxford score), serum metal ion levels (cobalt and chromium), and radiographs. A computed tomographic scan (without metal suppression) was made. In patients who had a revision, tissue samples were histologically examined. RESULTS: Originally, there were 129 patients with 149 BHRs. Four patients (six hips; 4%) were lost to follow-up. Our final cohort consisted of 125 patients (143 hips). From this final cohort, eleven patients (twelve hips) had a revision, and three of them (three hips) had the revision before the present study was conducted. Seven patients (eight hips; 5.6%) had a revision because of a symptomatic pseudotumor. Survival analysis showed an implant survival rate of 87.5% at five years (failure was defined as a revision for any reason). A pseudotumor was found on computed tomography in thirty-nine patients (forty hips; 28%). Of those patients, ten (eleven hips; 28%) had complaints involving groin pain and discomfort, a noticeable mass, or paresthesia. Symptomatic pseudotumors were significantly larger than asymptomatic pseudotumors (a mean volume of 53.3 cm3 compared with 16.3 cm3; p = 0.05). A serum cobalt level of >85 nmol/L was a predictor for pseudotumor formation (odds ratio, 4.9). CONCLUSIONS: Pseudotumor formation occurred in 28% of hips after an average follow-up of forty-one months. Most pseudotumors (72.5%) were asymptomatic. Larger pseudotumors were associated with more complaints. Survival analysis showed an implant survival of 87.5% at five years. Failure occurred in 5.6% (eight) of 143 hips because of a symptomatic pseudotumor.

[Liver cirrhosis in diabetes mellitus; a complication not always recognized]. / Levercirrose bij diabetes mellitus, een niet altijd onderkende complicatie.

Non-alcoholic fatty liver disease is common among diabetic patients and carries the risk of non-alcoholic steatohepatitis (NASH) and progressive fibrosis and cirrhosis. This is illustrated by three patients with diabetes mellitus, two women aged 76 and 59, and a man aged 58. The first patient was referred to our clinic with ascites that appeared to be due to a previously unrecognized NASH associated with diabetes and which resulted in liver cirrhosis. She was treated with diuretics and subsequently remained stable. The male patient, suffering from overweight, had silently developed liver cirrhosis prompting referral to a transplantation centre. For this procedure he was put on a weight reduction programme. The third patient also had diabetes-associated liver cirrhosis, but was referred for transplantation when liver failure became inevitable. Because of the increasing prevalence of overweight and diabetes, there will be an increase in the number of patients with diabetes associated NASH and liver failure requiring transplantation.

Effect of modified Davidson's fixative on examined number of lymph nodes and TNM-stage in colon carcinoma.

AIMS: We evaluated the effect of modified Davidson's fixative (mDF) on the number of lymph nodes examined and staging in patients with colon carcinoma. METHODS: The results of two different fixation methods used in the pathological preparation of the resection specimens were analyzed. A traditional formalin preparation with manual dissection of all nodes was performed in 117 colon specimens between January 2003 and July 2004. After July 2004, the resected specimens of 125 patients was fixated in mDF. Differences in the retrieval and number of nodes and size of suspected nodal metastases were measured. All lymph nodes were stained with conventional H&E methods. RESULTS: The median number of examined nodes increased from 5 (0-17) to 13 (0-35) nodes after the introduction of mDF (p<0.001). The type of resection and the T-stage influenced the number of retrieved nodes significantly. The percentage of node-positive cases increased from 30% to 41% (p=0.077) with mDF, the median size of the retrieved lymph nodes decreased from 9 mm before to 6 mm after mDF (p<0.001) and more micrometastases were found (6% vs. 16%, p=0.03). CONCLUSIONS: With mDF technique more lymph nodes were retrieved in the resected colon specimens. Smaller nodes and more micrometastases were found, leading to more node positive patients.

Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive.

Since 1991, a nationwide histopathology and cytopathology network and archive is in operation in The Netherlands under the name PALGA, encompassing all sixty-four pathology laboratories in The Netherlands. The overall system comprises decentralized systems at the participating laboratories, a central databank, and a dedicated communication and information exchange tool. Excerpts of all histopathology and cytopathology reports are generated automatically at the participating laboratories and transferred to the central databank. Both the decentralized systems and the central system perform checks on the quality and completeness of excerpts. Currently, about 42 million records on almost 10 million patients are stored in the central databank. Each excerpt contains patient identifiers, including demographic data and the so-called PALGA diagnosis. The latter is structured along five classification axes: topography, morphology, function, procedure, and diseases. All data transfer and communication occurs electronically with encryption of patient and laboratory identifiers. All excerpts are continuously available to all participating pathology laboratories, thus contributing to the quality of daily patient care. In addition, external parties may obtain permission to use data from the PALGA system, either on an ongoing basis or on the basis of a specific permission. Annually, 40 to 60 applications for permission to use PALGA data are submitted. Among external users are the Dutch cancer registry, population-based screening programs for cancer of the uterine cervix and breast cancer in The Netherlands, and individual investigators addressing a range of research questions. Many scientific papers and theses incorporating PALGA data have been published already. In conclusion, the PALGA system is a unique system that requires a minimal effort on the part of the participating laboratories, while providing them a powerful tool in their daily practices.

Extra nodal growth as a prognostic factor in malignant melanoma.

AIM: Extra nodal growth (ENG) in lymph-node metastases may be an additional indicator for poor prognosis and increased loco-regional recurrence in patients with a cutaneous malignant melanoma (CMM). Most studies analyzing prognostic factors lack a proper definition or description of the histological criteria for extra nodal growth. The objective of this study was to evaluate this factor. METHODS: Retrospectively 94 patients with CMM and clinically lymph-node metastases were analysed. Metastatic lymph-nodes were evaluated for ENG and if present grouped in microscopic (<2 mm) or macroscopic (>2 mm) ENG. ENG was defined as metastatic tumour which clearly extends histologically through the nodal capsule into the perinodal fatty tissue or tumour involvement in the hilar region with interruption of the smooth outline of the (presumed) capsule. RESULTS: Ninety-four patients, median age 52 (6-92) years with CMM, median Breslow thickness 2.8 (0.2-11.0) mm. In 50 patients ENG was present (macroscopic: 32, microscopic: 18). The median follow-up was 59 (range 5-325) months. The number of loco-regional recurrence was 10; 4 in the group with and 6 in the group without ENG (n.s.). Five years survival of patients with ENG was 42% and without ENG 50% (n.s.). There was no significant difference in survival or loco-regional recurrence between microscopic or macroscopic ENG. CONCLUSION: ENG of lymph-node metastases of CMM is of no prognostic value and has no clinical impact.

Diffuse and intestinal type gastric carcinomas differ in their expression of apoptosis related proteins.

BACKGROUND: Gastric carcinomas can be divided into intestinal and diffuse types, with the last type having a worse prognosis. AIMS: To investigate whether specific patterns in the expression of apoptosis related proteins correlate with carcinoma type and/or prognosis METHODS: The expression of Fas, Bcl-2, Bax, Bcl-xl, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) was studied immunohistochemically and the extent of apoptosis and proliferation was investigated in 11 cases of intestinal type and in eight cases of diffuse type carcinoma. RESULTS: Fas was expressed in all intestinal type and in one diffuse type carcinoma. Bcl-xl was expressed in 10 of 11 intestinal type and in one of eight diffuse type carcinomas. Bcl-2 was expressed in lamina propria immune cells. iNOS was expressed in six of 11 intestinal type and in four of eight diffuse type carcinomas, and COX-2 was expressed in eight of 11 intestinal type and in six of eight diffuse type carcinomas. CONCLUSION: Fas and Bcl-xl expression can differentiate between intestinal type and diffuse type gastric carcinomas. No differences in apoptosis and proliferation between intestinal type and diffuse type gastric carcinomas were observed.

New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma.

The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research, new diagnostic techniques, such as Positron Emission Tomography and the introduction of the sentinel lymph node biopsy with advanced laboratory methods such as immuno-histochemical markers, and reverse transcriptase polymerase chain reaction, have been developed to facilitate early detection of metastatic melanoma. The role of these new techniques on the staging and surgical treatment of melanoma is discussed in this paper.

Is sentinel node biopsy beneficial in melanoma patients? A report on 200 patients with cutaneous melanoma.

AIM: The aim of this study was to evaluate the reliability and clinical impact of sentinel node biopsy, including preoperative lymphoscintigraphy and intraoperative lymphatic mapping in patients with cutaneous melanoma of the head, neck, trunk or extremities. METHODS: Two hundred patients (103 women, 97 men), median age 57 (range 21-86) years with cutaneous melanoma > or =1.0mm Breslow thickness and clinically negative lymph nodes participated in a single institutional prospective study from May 1995 to January 2000. Primary melanoma sites included: 22 head and neck (11%), 67 trunk (34%), 29 upper extremity (14%) and 82 lower extremity (41%). The median Breslow thickness was 2.5 (range 1.0-20.0)mm. Preoperative dynamic and static lymphoscintigraphy, intraoperative blue dye and a gamma detection probe were used. If histological examination with HE or IHC showed metastases, therapeutic lymph node dissection (TLND) was performed. RESULTS: Sentinel node(s) could be identified in 197 patients (99%); 393 sentinel nodes (mean: 2.0 per patient, range 1-7) were removed from 241 basins. Three procedures failed in the head and neck region. In 167 patients, the sentinel nodes were both blue and radioactive (85%); in 26 patients, they were only radioactive (13%) and in four patients only blue (2%). In total, 150 patients had tumour-negative sentinel nodes (76%). During a median follow-up of 47 (range 24-79) months, nodal recurrence in a negative mapped basin was documented in six patients of which isolated recurrence was in two patients and recurrence together with locoregional recurrence in four patients (false negative rate 6/54=11%). Estimated three-year recurrence-free survival in the node-negative patients and node-positive patients was 83 and 66% respectively (P<0.05). The overall survival at three years was 92 and 73% respectively (P<0.05). CONCLUSION: Sentinel node biopsy provides accurate staging and important prognostic information. The final place of sentinel node biopsy is still undefined, and therefore sentinel node biopsy is still considered as an experimental surgical staging procedure.

Expression of apoptosis-related proteins in Barrett's metaplasia-dysplasia-carcinoma sequence: a switch to a more resistant phenotype.

Barrett's esophagus, or columnar-lined esophagus (CLE), is a premalignant disorder in which the stratified squamous epithelium is replaced by metaplastic epithelium. To gain more insight into the process of carcinogenesis in CLE, we studied several factors involved in the apoptotic pathway in biopsies with gastric metaplasia (GM), intestinal metaplasia (IM), dysplasia, and/or adenocarcinoma. Immunohistochemistry was performed for Fas, Bcl-2, Bax, Bcl-xl, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). Fas staining was positive in the epithelium of all biopsies from patients with CLE but negative in normal gastric mucosa. Fas staining was positive in all tumor cells of the 8 cases containing adenocarcinoma. Bcl-2 was positive in lamina propria immune cells of all specimens. Bax staining was positive in the epithelium of all biopsies, including tumor cells. Bcl-xl was positive in dysplasia and tumor cells, but negative in 8 of 17 biopsies containing IM. iNOS was positive in 20 of 21 biopsies with IM and in 4 of 8 dysplasia biopsies. COX-2 was positive in 7 of 8 adenocarcinomas. We conclude that the apoptotic balance in the transformation from IM to adenocarcinoma switches to an antiapoptotic phenotype because of increased Bcl-xl expression and decreased Bax expression. Fas can be used as a marker for the differentiation of gastric mucosa and metaplasia in the esophagus. iNOS is highly positive in CLE-associated intestinal metaplasia. COX-2 is negative in nonmalignant CLE. Therefore, pharmacologic inhibition of COX-2 activity is unlikely to be effective in the preventing CLE-associated adenocarcinoma. There was no clear correlation between iNOS expression and activation of proapoptotic and antiapoptotic genes.

Chronic blockade of angiotensin II action prevents glomerulosclerosis, but induces graft vasculopathy in experimental kidney transplantation.

Long-term renin-angiotensin system blockade is beneficial in a variety of renal diseases. This study examines the long-term (34 weeks) effects of the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor type I blocker L158,809 in the Fisher to Lewis rat model of chronic renal transplant failure. Treatment in allografted rats with lisinopril or L158,809 was initiated 10 days after transplantation, or at the time when proteinuria exceeded 50 mg/24 h. Untreated allografts and syngrafts served as controls. In contrast to syngrafts, untreated allografts developed proteinuria, hypercholesterolaemia, interstitial damage, and glomerulosclerosis. Lisinopril or L158,809 treatment in allografts starting at day 10 after transplantation completely prevented this, with the exception of interstitial damage, but this treatment also caused a reduction in blood pressure and renal function. Moreover, the intimal surface area of the renal arteries was dramatically increased in allografts treated with either lisinopril or L158,809 compared with untreated allografted rats. Treatment once proteinuria had developed was less effective in preventing glomerulosclerosis, but also caused less intimal expansion. Thus, chronic renin-angiotensin system blockade preserves glomerular morphology in the absence of proteinuria, but enhances intimal hyperplasia and reduces renal function in experimental transplantation. In view of these results, it should be questioned whether such treatment benefits renal transplant patients in the long term.

The content and distribution of troponin I, troponin T, myoglobin, and alpha-hydroxybutyric acid dehydrogenase in the human heart.

We studied the content and distribution of heart-specific markers troponin I and troponin T in relation to conventional non-heart specific myoglobin and alpha-hydroxybutyric acid dehydrogenase (HBD) in the hearts of 34 patients who died of various causes. Tissue was obtained from the right and left ventricles, the interventricular septum, and the right and left atria. We found significant differences in the contents expressed per gram wet weight tissue in the right and left ventricles for troponin I (by 1 of the 2 methods used), troponin T, myoglobin, and HBD and no differences per gram of protein. The biochemical contents per gram wet weight tissue and per gram protein were significantly lower in the right and left atria for all studied markers compared with the right and left ventricles. No significant differences were found in biochemical contents between the right and left atria. These findings imply that estimation of myocardial damage through cardiac markers levels in serum depends on the site of injury (atrium or ventricle). Comparison of myocardial injury among individuals using marker levels in serum is not reliable because of the varied ranges of markers in tissue contents.

Frozen section investigation of the sentinel node in malignant melanoma and breast cancer.

BACKGROUND: Intraoperative frozen section investigation allows immediate regional lymph node dissection when the sentinel node contains tumor. The purpose of this study was to determine the sensitivity of frozen section diagnosis of the sentinel node in melanoma and breast cancer patients. METHODS: A total of 177 sentinel nodes from 99 melanoma patients and 444 lymph nodes from 262 breast cancer patients were assessed by frozen section investigation. Nodes were bisected, and a complete cross-section was obtained for frozen section. Step sections at three levels were made of the remaining lymphatic tissue and were stained with hematoxylin and eosin and S100/HMB45 (melanoma) or CAM5.2 (breast cancer) to obtain a final pathological diagnosis. RESULTS: Frozen section investigation revealed metastases in 8 of 17 node-positive melanoma patients (47%). Seventy-one of 96 breast cancer patients (74%) with lymph node metastases were identified with frozen section. The specificity was 100% and 99%, respectively. CONCLUSION: The sensitivity of intraoperative frozen section investigation of sentinel nodes was 47% in melanoma patients and 74% in breast cancer patients. Frozen section examination allows immediate axillary lymph node dissection in the majority of node-positive breast cancer patients. Frozen section analysis is not recommended in patients with melanoma.

Renal expression of endothelial and inducible nitric oxide synthase, and formation of peroxynitrite-modified proteins and reactive oxygen species in Wegener's granulomatosis.

To investigate the role of nitric oxide (NO) in glomerular inflammation, the expression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was studied in conjunction with inflammatory cell influx, H2O2 production, and the formation of nitrotyrosines in renal biopsies from patients with Wegener's granulomatosis (WG). Renal cryostat sections from patients with WG (n=15) were stained by immunohistochemistry for eNOS, iNOS, endothelial cells (CD31), nitrotyrosines, polymorphonuclear cells (PMNs, CD15), and monocytes/macrophages (CD14, CD68). Production of H2O2 was identified by enzyme cytochemistry using diaminobenzidine. In control tissues, strong staining for eNOS was found in glomerular and interstitial tubular capillaries and cortical vessels. A significant reduction in eNOS expression was found in WG biopsies, which was associated with a reduction in CD31 expression. Expression of iNOS was found in infiltrating inflammatory cells, mainly located in the interstitium. H2O2-producing cells were detected in glomeruli and were abundantly present in the interstitium. Nitrotyrosine-positive cells, however, were almost exclusively found in the interstitium. It is concluded that renal inflammation in WG is associated with the induction of iNOS in inflammatory cells and the formation of nitrotyrosines. Expression of eNOS in glomerular capillaries is lost, most likely due to endothelial cell damage. These results suggest that decreased NO production by endothelial cells, in conjunction with increased NO production by iNOS-positive inflammatory cells, is involved in renal tissue injury in WG.

Frozen section analysis of sentinel lymph nodes in melanoma patients.

BACKGROUND: The sentinel lymph node biopsy (SLNB) is a diagnostic or staging option in the treatment of patients with cutaneous malignant melanoma (CMM) and is investigated intensively. A positive SLNB has appeared to identify patients who might have benefited from a lymph node dissection (LND). Intraoperative frozen section analysis (FSA) of the sentinel lymph node (SLN) during surgery would allow SLNB and LND to be performed in the same procedure. In the current study, we tested the reliability of FSA on the sentinel lymph node in patients with CMM. METHODS: Before definitive treatment of their melanomas began, FSA was performed on the SLNBs of 58 patients, whose median age was 56 (22-81) years, and who were 55% male and 45% female. Serial sections (500 micrometer interval), stained with routine hematoxylin and eosin and immunohistochemistry (S-100 and HMB-45), obtained definitive histology of the sentinel lymph node. RESULTS: Detection of the sentinel lymph node was possible in 56 patients (97%). Sixty-one SLNBs were performed in these patients. FSA detected metastases in 5 of 108 SLN (5%) in 5 patients. This was upgraded after definitive histology to 13 SLN (12%) in 11 patients (20%). Sensitivity of the FSA was 38%. After a median follow-up of 35 (range: 24-54) months, the false-negative rate of the SLN was 4% (2 patients). CONCLUSION: The combination of the low sensitivity of FSA and a finding that only 12% of the SLNBs contained metastases does not justify routine use of FSA on the SLN of patients with CMM.

Limitations of the nested reverse transcriptase polymerase chain reaction on tyrosinase for the detection of malignant melanoma micrometastases in lymph nodes.

The specificity and sensitivity of the nested reverse transcriptase polymerase chain reaction (RT-PCR) on tyrosinase was studied, for the detection of micrometastases of malignant melanoma. The specificity was assessed in the blood of six healthy donors, four patients with non-melanoma cancers of which one patient was treated with granulocyte-colony stimulating factor. Lymph nodes of nine patients without malignant melanoma were tested and four cell lines of various other tumours. Six of the nine non-melanoma lymph nodes were positive in this assay. The sensitivity was tested in a spike experiment in vitro, using a melanoma cell line. The detection limit was ten melanoma cells per 10(7) peripheral blood lymphocytes.

Lymphatic mapping with intralesional tracer administration in breast carcinoma patients.

BACKGROUND: The objectives of the study were to determine how often a sentinel lymph node is visualized by lymphoscintigraphy in breast carcinoma patients, how often the sentinel lymph node is identified during surgery, and the sensitivity of these procedures to identify the presence of axillary lymph node metastasis. METHODS: A total of 136 patients were enrolled in 2 hospitals. Preoperative dynamic and static lymphoscintigraphy were performed; in addition, both a vital dye and a gamma detection probe were used intraoperatively. The tracers were injected into the primary lesion. Sentinel lymph node biopsy was followed by completion axillary lymph node dissection. The sentinel lymph nodes and other axillary lymph nodes were examined routinely and by immunohistochemical staining. RESULTS: A sentinel lymph node was visualized by lymphoscintigraphy in 118 patients (87%). During the operation a sentinel lymph node was localized in 126 patients (93%). A total of 224 sentinel lymph nodes were harvested (average of 1.7 and range of 1-4 sentinel lymph nodes per patient). Of all the sentinel lymph nodes, 37 were blue (17%), 68 were radioactive (30%), and 119 were both blue and radioactive (53%). The sentinel lymph nodes contained metastatic disease in 56 patients (44%). Three sentinel lymph node biopsies were false-negative (sensitivity 95%). CONCLUSIONS: Sentinel lymph node biopsy with preoperative lymphoscintigraphy after intralesional tracer administration and intraoperative use of both a gamma detection probe and a vital dye is a reliable technique for staging the axilla of breast carcinoma patients.

Nitric oxide production and nitric oxide synthase expression in acute human renal allograft rejection.

BACKGROUND: Nitric oxide (NO) is produced by nitric oxide synthases (NOS), which are either constitutively expressed in the kidney or inducible, in resident and infiltrating cells during inflammation and allograft rejection. NO is rapidly degraded to the stable end products nitrite and nitrate, which can be measured in serum and urine, and may serve as noninvasive markers of kidney allograft rejection. METHODS: Total nitrite and nitrate levels (NOx) were measured in serum and urine thrice weekly after an overnight fast in 18 consecutive patients following renal cadaveric transplantation. Inducible NOS (iNOS) and endothelial NOS (eNOS) expression was immunochemically determined in renal biopsy specimens with or without acute rejection (AR). RESULTS: Serum NOx levels increased days before AR and were significantly higher at the moment of AR (27+/-12.4 micromol/L) compared with recipients with an uncomplicated course (13+/-7.6 micromol/L), but not compared with recipients with cyclosporine (CsA) toxicity (20+/-13.0 micromol/L). Urinary NOx levels were significantly lower during AR (20+/-13.6 micromol/mmol creatinine) compared with an uncomplicated course (64+/-25.2 micromol/mmol creatinine) or CsA toxicity (53.8+/-28.3 micromol/mmol creatinine). Interstitial and glomerular iNOS expression was significantly increased in biopsy specimens showing AR. Unexpectedly, glomerular eNOS expression was significantly decreased in patients with AR. CONCLUSIONS: This study reports differences in NOx levels in serum and urine, which may help discriminate AR episodes from an uncomplicated course or CsA toxicity. As expected, renal iNOS expression is increased in acute allograft rejection. The decrease in glomerular eNOS expression suggests an intriguing link between acute and chronic rejection.

Systemic factors are involved in the pathogenesis of proteinuria-induced glomerulosclerosis in adriamycin nephrotic rats.

This study aims to dissociate the respective roles of systemic nephrosis and of the intrarenal effects of proteinuria in the pathogenesis of focal segmental glomerulosclerosis (FGS) in adriamycin nephrosis. To this purpose, this study examined proteinuria and FGS in bilateral (BAP) and unilateral proteinuria (UAP) in two different rat strains. UAP was obtained by protecting one kidney from exposure to adriamycin by temporary clipping of one renal artery during adriamycin injection. At sacrifice (week 12), FGS was present in BAP and in exposed kidneys in UAP, but not in unexposed kidneys. FGS correlated significantly with proteinuria per kidney in BAP and UAP. Remarkably, for a given proteinuria per kidney, the sclerosis score was higher in BAP than in UAP, reflected by a higher ratio of FGS score per mg proteinuria per kidney (Wistar: 0.09 +/- 0.01 in BAP versus 0.05 +/- 0.01%/mg protein per d in UAP, P < 0.05; Lewis: 0.12 +/- 0.01 in BAP versus 0.07 +/- 0.01%/mg protein per d in UAP, P < 0.05), indicating that the local damaging effects of proteinuria are modified by other factors. Cholesterol correlated with total proteinuria in BAP and UAP. FGS score was positively correlated with cholesterol. The latter correlation was similar in BAP and UAP, indicating that cholesterol was a more uniform predictor for FGS than proteinuria per kidney. This was independent of strain-specific factors. On multilinear regression analysis, cholesterol turned out to be the most consistent predictor of FGS in proteinuric kidneys, with a stronger predictive value than proteinuria per kidney. It is concluded that although systemic sequelae of nephrosis do not induce renal damage in nonproteinuric kidneys, they modify the severity of proteinuria-induced FGS in proteinuric kidneys.

Sentinel node biopsy as a surgical staging method for solid cancers.

The sentinel node is the first lymph node that drains a primary tumour. If this lymphatic drainage occurs in a step-wise fashion, this lymph node reflects the pathological status of the remaining lymph node basin. The day before the operation, a total dose of 60 MBq 99mTc nanocolloid is injected around the primary tumour for lymphoscintigraphy. On the day of surgery, 1 ml of blue dye is injected around the primary tumour to facilitate sentinel lymph node detection. After making a small incision over the regional lymph node region, the sentinel node can be detected using a hand-held gamma ray detection probe; the sentinel lymph node and the afferent lymphatic vessels will be stained blue. Sentinel node biopsy has proved useful for malignant melanoma, breast cancer, penile cancer, vulvar cancer, Merkel cell carcinoma and thyroid cancer. New studies are described on breast cancer and malignant melanoma. Gamma-probe-guided localization of radiolabelled lymph nodes can direct the surgeon non-invasively to the exact location of the sentinel node. Once localized with a gamma probe, it is quick and easy to remove the sentinel node through a small incision. Discriminating the node from other tissue can be aided by blue dye which stains the lymph node. It appears that both radioactivity and blue dye are complementary for locating the sentinel node.