Breast Cancer Detection by Preoperative Imaging in Reduction Mammaplasty Patients: A Single Center Study of 918 Patients.

BACKGROUND: The role of preoperative imaging and the usability of different imaging modalities is highly variable and controversial in reduction mammaplasty patients. Our study describes the imaging process in a single center in regard to modality selection, age and timing, and of the association between imaging and histopathological findings in reduction mammaplasty specimens. METHODS: Nine hundred eighteen women, who underwent reduction mammaplasty during 1.1.2007-31.12.2011, were retrospectively reviewed for demographics, preoperative imaging, further preoperative examinations, and pathology reports. RESULTS: Preoperative imaging had been conducted for 89.2% (n = 819) of the patients. In 49 (6.0%) patients, suspicious preoperative imaging led to further examinations revealing 2 high-risk lesions (atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS)), and 2 cancers preoperatively. Postoperatively abnormal histopathology specimens were revealed in 88 (10.4%) patients. The incidence of high-risk lesions was 5.5% (n = 47), and the incidence of cancer was 1.2% (n = 10). Preoperative imaging was normal (BI-RADS 1 and BI-RADS 2) in 80.8% of these patients. The sensitivity of the preoperative imaging for cancer detection was 20.0%, and the specificity was 100.0%. CONCLUSIONS: Preoperative imaging and further examinations do not sufficiently detect malignant or cancer risk-increasing findings. Therefore, histopathological analysis of reduction mammaplasty specimens seems mandatory.

Screening primary sclerosing cholangitis and biliary dysplasia with endoscopic retrograde cholangiography and brush cytology: risk factors for biliary neoplasia.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is associated with increased risk of biliary dysplasia and cholangiocarcinoma (CCA). The aim of this study was to evaluate the role of early endoscopic retrograde cholangiography (ERC) with systematic brush cytology to identify risk factors associated with biliary neoplasia. PATIENTS AND METHODS: Patients who were referred for their first ERC for suspicion of PSC between January 2006 and October 2011 were included in the study. Brush cytology specimens were scored as benign, suspicious, or malignant. End points were CCA, biliary dysplasia, benign histology, or benign disease course for ≥ 2 years. RESULTS: PSC was diagnosed in 261 patients (125 men, 136 women), most of whom were asymptomatic (n = 211). Cholangiographic changes were mild in 57.1 %. Men presented with advanced disease more often than women. Brush cytology was benign in 243, suspicious in 16, and malignant in 2 patients. Follow-up completed in 249 patients indicated a benign disease course in 232 patients. Seven patients were diagnosed with CCA and eight had biliary dysplasia in the explanted liver. Thus, 15 patients had biliary neoplasia, and suspicious or malignant brush cytology had been detected in 8 of them at initial brushing. Advanced extrahepatic cholangiographic changes with elevated aminotransferases at diagnosis seemed to be associated with increased risk of biliary neoplasia. CONCLUSIONS: Even in mostly asymptomatic patients with PSC, 42.9 % had advanced disease and 6.9 % presented with suspicious or malignant brush cytology at first ERC. Advanced extrahepatic ERC changes with elevated aminotransferases at diagnosis might be risk factors for biliary neoplasia.

Biliary dysplasia in patients with primary sclerosing cholangitis: additional value of DNA ploidity.

BACKGROUND: Detection of biliary dysplasia in PSC is essential for proper timing of liver transplantation to prevent the development of cholangiocancer, which is considered a contraindication for liver transplantation in most centres. In patients with PSC, differential diagnosis of benign, premalignant and malignant biliary strictures is difficult. AIMS: This prospective study aimed to evaluate the role of DNA analysis in combination with brush cytology, scored ERCP findings, and tumour markers to detect hepatobiliary dysplasia and malignancy. MATERIAL AND METHODS: Brush samples for cytology and for evaluation of DNA content analysed with flow cytometry came from 102 consecutive PSC patients referred for ERCP. Symptoms, serum Ca19-9 and CEA were determined at the time of index biliary examination. ERCP findings were scored for intra- and extrahepatic changes. The end-points were liver transplantation or diagnosis of malignancy or dysplasia. RESULTS: Most of the patients were asymptomatic at the time of ERCP: 73% had no symptoms, and 12% had only mild symptoms. An aneuploid DNA content was evident in 20 (20%) patients, and cells suspected for malignancy in 22 (21%). Seven patients had both aneuploidity and cytology (7%) suspicious for malignancy. An end-point, diagnosis of malignancy or liver transplantation was achieved in 42 patients. Combining DNA ploidity and cytology in patients at the end-point, sensitivity was 72%, specificity 82%, positive predictive value 86% and negative predictive value 67%. DISCUSSION AND CONCLUSION: In this mostly asymptomatic PSC-patient population, 33% demonstrated abnormal brush cytology or aneuploidity. Determining DNA ploidy and brush cytology during ERCP offers a useful tool for identifying those PSC patients who are at high risk of developing cholangiocancer.

Long-term results of ablation with antireflux surgery for Barrett's esophagus: a clinical and molecular biologic study.

BACKGROUND: The initial results from ablation therapy for metaplastic/dysplastic Barrett's esophagus (BE) are promising, but the results of extended follow-up evaluation are seldom reported. METHODS: Neodymium:yttrium-aluminum-garnet laser ablation and successful antireflux surgery for 18 patients with metaplastic BE primarily resulted in the total histologic eradication of BE in 15 patients (83%). After antireflux surgery, the healing of gastroesophageal reflux disease (GERD) was objectively verified in all the patients. At late follow-up evaluation, endoscopy, conventional histology, molecular oxidative stress analyses in comparison with normal control conditions (8-hydroxydeoxyguanosine [8-OHdG], superoxide dismutase [SOD], glutathione [GSH], myeloperoxydase [MP]), and immunohistochemistry (p53, and Cdx2, caudal-related homeobox gene 2, marking intestinal differentiation) of the neosquamous epithelium were performed. RESULTS: At the end of the follow-up period (range, 3-15 years; mean, 8 years), intestinal metaplasia without dysplasia was detected histologically in eight patients (44%). Six patients had macroscopic BE (mean length, 3.5 cm; range 1-10 cm). The neosquamous epithelium was histologically normal, with no underlying columnar tissue. The fundoplication was endoscopically normal in 14 patients (82%). The 8-OHdG level was higher in the neosquamous epithelium than in the control conditions in the distal esophagus (4.3 vs. 0.52; P = 0.0002) and the proximal esophagus (1.8 vs. 0.95; P = 0.006). Likewise, SOD activity was higher in the neosquamous epithelium (0.38 vs. 0.12; P = 0.0005), whereas MP activity and GSH levels remained normal. Three patients showed slight nuclear p53 expression (typical in normal inflammatory reactions), whereas Cdx2 positivity was confined to one case with recurrent intestinal metaplasia. CONCLUSIONS: The neosquamous mucosa, generated by the ablation of BE and the treatment of GERD with fundoplication, was stable during long-term follow-up evaluation in two-thirds of the patients with initial eradication. It had normal p53 expression and no Cdx2 protein expression. The oxidative stress of the neosquamous esophagus remained high, although the clinical significance of this is unclear.

Endocervical Cytology: Inter- and Intra-Observer Variability in Conventional Pap Smears.

INTRODUCTION: Although the cytological diagnostic criteria for cervical squamous and glandular lesions are established by the Bethesda System for Reporting Cervical Cytology, the reproducibility of the diagnosis of these lesions has been shown to be variable in previous studies. At best, occasional good kappa (κ) values were reached both inter- and intra-observerly. Generally, consensus on high-grade lesions has been better compared to milder changes. METHODS: Altogether, 167 conventional Pap smears from 50 patients with histologically confirmed endocervical adenocarcinomas (EAC) and adenocarcinomas in situ (AIS) and from 28 patients with histologically proven high-grade intraepithelial lesions were analyzed by four cytopathologists. Twenty of the smears were later re-evaluated by the same cytopathologists. κ-values between cytopathologists in the categories of squamous versus glandular, negative for intraepithelial lesion or malignancy (NILM), atypical, and preneoplastic/neoplastic were calculated. The diagnostic Pap smears of EAC and AIS with best and worst consensus between observers were then morphologically analyzed. RESULTS: The reproducibility ranged from poor to substantial. The overall κ-values between the four cytopathologists were 0.412, 0.314, 0.272, and 0.082, respectively, in the categories of preneoplastic/neoplastic, squamous versus glandular, NILM, and atypical. Overall intra-observer κ-values were correspondingly 0.491, 0.616, 0.345, and 0.241. In the diagnostic smears of AIS and EAC, the nuclear size >2 times the normal and nuclear pleomorphism were the commonest features associated with good diagnostic consensus and the lack of nuclear enlargement and degenerative changes were associated with poor consensus. CONCLUSIONS: The reproducibility of preneoplasia/neoplasia diagnoses was better than that of atypia and NILM both in the inter- and intra-observer part in this study. In the smears from AIS and EAC patients, general neoplasia-associated features were more common in samples with good agreement by the four cytopathologists of the neoplastic nature and the endocervical origin of the lesion.

Metastatic outgrowth encompasses COL-I, FN1, and POSTN up-regulation and assembly to fibrillar networks regulating cell adhesion, migration, and growth.

Although the outgrowth of micrometastases into macrometastases is the rate-limiting step in metastatic progression and the main determinant of cancer fatality, the molecular mechanisms involved have been little studied. Here, we compared the gene expression profiles of melanoma lymph node micro- and macrometastases and unexpectedly found no common up-regulation of any single growth factor/cytokine, except for the cytokine-like SPP1. Importantly, metastatic outgrowth was found to be consistently associated with activation of the transforming growth factor-beta signaling pathway (confirmed by phospho-SMAD2 staining) and concerted up-regulation of POSTN, FN1, COL-I, and VCAN genes-all inducible by transforming growth factor-beta. The encoded extracellular matrix proteins were found to together form intricate fibrillar networks around tumor cell nests in melanoma and breast cancer metastases from various organs. Functional analyses suggested that these newly synthesized protein networks regulate adhesion, migration, and growth of tumor cells, fibroblasts, and endothelial cells. POSTN acted as an anti-adhesive molecule counteracting the adhesive functions of FN1 and COL-I. Further, cellular FN and POSTN were specifically overexpressed in the newly forming/formed tumor blood vessels. Transforming growth factor-beta receptors and the metastasis-related matrix proteins, POSTN and FN1, in particular, may thus provide attractive targets for development of new therapies against disseminated melanoma, breast cancer, and possibly other tumors, by affecting key processes of metastasis: tumor/stromal cell migration, growth, and angiogenesis.

Point-of-Care Digital Cytology With Artificial Intelligence for Cervical Cancer Screening in a Resource-Limited Setting.

Importance: Cervical cancer is highly preventable but remains a common and deadly cancer in areas without screening programs. The creation of a diagnostic system to digitize Papanicolaou test samples and analyze them using a cloud-based deep learning system (DLS) may provide needed cervical cancer screening to resource-limited areas. Objective: To determine whether artificial intelligence-supported digital microscopy diagnostics can be implemented in a resource-limited setting and used for analysis of Papanicolaou tests. Design, Setting, and Participants: In this diagnostic study, cervical smears from 740 HIV-positive women aged between 18 and 64 years were collected between September 1, 2018, and September 30, 2019. The smears were digitized with a portable slide scanner, uploaded to a cloud server using mobile networks, and used to train and validate a DLS for the detection of atypical cervical cells. This single-center study was conducted at a local health care center in rural Kenya. Exposures: Detection of squamous cell atypia in the digital samples by analysis with the DLS. Main Outcomes and Measures: The accuracy of the DLS in the detection of low- and high-grade squamous intraepithelial lesions in Papanicolaou test whole-slide images. Results: Papanicolaou test results from 740 HIV-positive women (mean [SD] age, 41.8 [10.3] years) were collected. The DLS was trained using 350 whole-slide images and validated on 361 whole-slide images (average size, 100 387 × 47 560 pixels). For detection of cervical cellular atypia, sensitivities were 95.7% (95% CI, 85.5%-99.5%) and 100% (95% CI, 82.4%-100%), and specificities were 84.7% (95% CI, 80.2%-88.5%) and 78.4% (95% CI, 73.6%-82.4%), compared with the pathologist assessment of digital and physical slides, respectively. Areas under the receiver operating characteristic curve were 0.94 and 0.96, respectively. Negative predictive values were high (99%-100%), and accuracy was high, particularly for the detection of high-grade lesions. Interrater agreement was substantial compared with the pathologist assessment of digital slides (κ = 0.72) and fair compared with the assessment of glass slides (κ = 0.36). No samples that were classified as high grade by manual sample analysis had false-negative assessments by the DLS. Conclusions and Relevance: In this study, digital microscopy with artificial intelligence was implemented at a rural clinic and used to detect atypical cervical smears with a high sensitivity compared with visual sample analysis.

[Reporting of thyroid fine needle samples is changing in Finland--the Bethesda system in thyroid cytology]. / Bethesda-järjestelmä kilpirauhasen sytologiassa.

A recommendation for the reporting of thyroid cytological specimens was made as the consensus of the expert meeting arranged by the U.S. National Cancer Institute (NCI). This Bethesda system will replace the former Papa classes also in thyroid cytology. The new Bethesda classification considers the representativeness of the thyroid specimen, and the classification is based on the correlation of the underlying histological change with the cytological report. In particular, follicular tumors and suspicion of them are separated from other tumors into their own group. The new system will bring about a significant improvement to the reports of thyroid cytological specimens.

Spontaneous recovery of myocardial function after ligation of Ameroid-stenosed coronary artery.

OBJECTIVES: We aimed to assess the spontaneous healing of myocardial function after occlusion of a chronically stenosed coronary vessel in a porcine model. DESIGN: Ischemia and infarction was produced by Ameroid constrictor placement and a subsequent ligation of the left circumflex artery. Cardiac MRI and 18FDG-PET were performed one and five weeks later. Ki67 staining was used to identify proliferating cells. RESULTS: Restoration of perfusion defect was detected by MRI (p=0.0065), reduced systolic function of the lateral segment spontaneously recovered (p=0.03). There was also a suggestive raise in impaired ejection fraction (p=0.06). Left ventricular early diastolic filling and peak filling rate were substantially improved (p=0.039 and p=0.0078). Scar size reduced (p=0.03). On the 18FDG-PET, deranged metabolism was alleviated (p=0.03). Cardiomyocytes with positive Ki-67 staining were located principally in the non-infarcted myocardium as compared to the infarction or border areas (p=0.037). CONCLUSIONS: We demonstrated spontaneous functional healing of ischemic and infarcted left ventricle, suggesting border zone perfusion recovery. Scar reduction was detected. Different pattern of myocyte proliferation between infarction and non-ischemic myocardium was seen.

Improved diastolic function after myoblast transplantation in a model of ischemia-infarction.

OBJECTIVES: The aim of this study was to evaluate the effect of myoblast transplantation on left ventricular function, perfusion, and scar formation after compromised coronary flow. DESIGN: A coronary vessel with Ameroid-induced stenosis was ligated and skeletal muscle was biopsied for isolation and cultivation of myoblasts. Two weeks after ligation, animals were randomly selected to receive intramyocardial injections of 2 x 10(6) myoblasts or vehicle. Fifteen animals survived the whole study period (n=9 and n=6, respectively). All animals underwent cardiac magnetic resonance imaging (MRI) and angiography pretreatment and four weeks posttreatment. RESULTS: Peak filling rate of the left ventricle improved in the myoblast group (p=0.0048), but not in the control group. Peak ejection rate and duration of diastole improved only in the myoblast group (p=0.049 and p=0.0039, respectively). Ejection fraction or local thickening did not change. Fibrosis and perfusion were similar in both groups, but more microvessels were present histologically in the myoblast group. CONCLUSIONS: In this preclinical study, autologous myoblast transplantation improved ischemic heart function via enhanced diastolic filling of the left ventricle.

Overexpression of HSP27 and HSP70 is associated with decreased survival among patients with esophageal adenocarcinoma.

BACKGROUND: Overexpression of heat shock proteins (HSPs) is associated with several malignancies and contributes to the development, progression, and metastasis of cancer, in addition to the inhibition of cellular death. In recent years, there has been active research into using HSP inhibitors in several malignancies. Due to the poor prognosis of esophageal adenocarcinoma (EAC), it would be valuable to find new biomarkers for the development of cancer treatments. AIM: To evaluate the expressions of HSP27 and HSP70 and their effect on survival in EAC. METHODS: Immunohistochemical analyses and evaluations of HSP27 and HSP70 expression were performed on all available samples from 93 patients diagnosed with EAC between 1990 and 2007 at two university hospitals. Fifteen cases with Barrett's metaplasia and 5 control cases from the same patient population were included in the analysis. HSP expression was quantitatively assessed and classified as high or low. Kaplan-Meier analyses and Cox regression models adjusting for age and sex as well as tumor site, stage, and grade were used to evaluate the effect on survival. RESULTS: Tumor stage and surgical treatment were the main prognostic factors. High HSP27 expression in cancer cases was a strong negative predictive factor, with a mean survival of 23 mo compared to the 49 mo in cases with a low expression (P = 0.018). The results were similar for HSP70, with a poorer survival of 17 mo in cases with high HSP70 expression, in contrast to 40 mo (P = 0.006) in cases with a low expression. A Cox regression survival analysis was performed, adjusting for possible confounding factors, and higher HSP27 and HSP70 expressions remained an independent negative prognostic factor. The HSPs' correlation with survival was not affected by cancer treatments. When the analysis was adjusted for all factors, the odds ratios for HSP27 and HSP70 were 3.3 (CI: 1.6-6.6, P = 0.001) and 2.2 (CI: 1.2-3.9, P = 0.02), respectively. CONCLUSION: HSP27 and HSP70 overexpression is associated with poor survival in EAC, which is, to the best of our knowledge, reported for the first time.

CMV increases tubular apoptosis through the TNF-alpha-TNF-R1 pathway in a rat model of chronic renal allograft rejection.

INTRODUCTION: Destruction of transplanted kidneys through chronic allograft nephropathy [CAN], also known as chronic rejection, is the greatest obstacle in successful kidney transplantation. Causes behind CAN are many, from pre-transplant causes to infections. Viral infections, especially CMV, are a risk factor for chronic rejection. We have previously developed a rat kidney transplant model, in which CMV enhances the development of chronic rejection under triple drug treatment. In this model we have now further studied the routes of apoptosis in virus induced early CAN vs. the routes of apoptosis in a later developing non-infectious CAN. MATERIALS AND METHODS: Renal transplantations were performed in a strain combination of DA/BN under immunosuppression. One group of animals was infected with RCMV and the other was left uninfected. The grafts were harvested on days 3-40 after transplantation. Apoptotic cells were visualised by in situ terminal transferase mediated dUTP nick end labelling [TUNEL] from paraffin embedded, formalin fixed kidney grafts. Cytokines were labelled imunohistochemically from frozen sections, among them tumour necrosis factor alpha [TNF-alpha] and its receptor-protein 1 [TNF-R1] as well as CD 95 [FAS], caspase 3 and CD14. The results were semi-quantitatively scored from 0 to 3+ over various tissues structures separately. RESULTS: In the CMV infected grafts, we could demonstrate a more intense TUNEL reaction in tubular epithelium [2.0+/-1.0 vs. 0.8+/-0.5 at day 14, P<0.05] as well as an earlier increase in the expression TNF-alpha in the vascular endothelium [2.0+1.0 vs. 0.0+0.0 at days 3-5, P<0.05] than in the non-infected group. There was also an earlier increase in the tubular TNF-R1 expression [2.2+0.8 vs. 1.0+0.0 at days 5-7, P<0.05]. There was no difference in the expression of CD14, caspase 3 or FAS between the groups. CONCLUSIONS: CMV enhanced development of CAN was associated with tubular apoptosis and concomitant increase of TNF-alpha-TNF-R1, rather than the FAS-FAS-ligand activation.

Cell Block in Cytological Diagnostics: Review of Preparatory Techniques.

OBJECTIVE: The cell block (CB) technique refers to the processing of sediments, blood clots, or grossly visible tissue fragments from cytological specimens into paraffin blocks that can be cut and stained by the same methods used for histopathology. The technique brings additional tissue architectural information. CB can be used for ancillary techniques such as immunocytochemistry and molecular techniques. STUDY DESIGN: We reviewed the literature on the various preparatory techniques of CBs. RESULTS: There is a wide range of preparatory techniques for CBs and no golden standard for CBs exists: tens of methods are used in various institutions. The majority of the methods are modified in house techniques with a few commercially available kits. The techniques most commonly used are the plasma/thrombin method, the agar method, and commercially available Histogel- and Cellient CB-methods. Dissatisfaction with the cellular yield of the CBs is common. CONCLUSIONS: In the CBs, the cytological material is preserved for future use, which is a tremendous advantage in the era of targeted therapy and biobanking. The CB is thus central to the future of cytology: more can be done with less material and with less invasiveness to the patient.

Should we routinely analyze reduction mammaplasty specimens?

BACKGROUND: Reduction mammaplasty is one of the most common plastic surgery procedures. Preoperative imaging and histopathology protocols vary among countries and institutions. We aimed to analyze the incidence of occult breast cancer and high-risk lesions in reduction mammaplasty specimens. We also analyzed whether patients with abnormal histopathology differed from the study population in terms of demographics. PATIENTS AND METHODS: In total, 918 women who underwent reduction mammaplasty from January 2007 to December 2011 were retrospectively reviewed for demographics, preoperative imaging, further preoperative examinations, pathology reports, and postoperative follow-up. RESULTS: Abnormal histopathological findings were revealed in 88 (10%) patients with a mean age of 49.5 ± 10.2 years. The incidence of breast cancer was 1.2%, and the incidence of high-risk lesions (atypical ductal and lobular hyperplasia and lobular carcinoma in situ) was 5.5%. Age and specimen weights were significantly higher in patients with abnormal histopathology. Eighty-one percent of patients with abnormal histopathology had normal preoperative imaging revealing two high-risk and two cancer findings. Two patients developed breast cancer in the same breast in which the high-risk lesion was originally detected. CONCLUSION: Women with abnormal histopathology cannot be sufficiently detected preoperatively. Therefore, histopathological analysis of reduction mammaplasty specimens seems mandatory. Reduction mammaplasty combined with subsequent histopathological examination offers a sufficient chance of detecting cancer and risk-increasing lesions that merits the cost of histopathology.

Reduction mammaplasty in patients with history of breast cancer: The incidence of occult cancer and high-risk lesions.

INTRODUCTION: Contralateral reduction mammaplasty is regularly included in the treatment of breast cancer patients. We analyzed the incidence of occult breast cancer and high-risk lesions in reduction mammaplasty specimens of women with previous breast cancer. We also analyzed if timing of reduction mammaplasty in relation to oncological treatment influenced the incidence of abnormal findings, and compared if patients with abnormal contralateral histopathology differed from the study population in terms of demographics. MATERIALS AND METHODS: The study consisted of 329 breast cancer patients, who underwent symmetrizing reduction mammaplasty between 1/2007 and 12/2011. The data was retrospectively analyzed for demographics, operative and histopathology reports, oncological treatment, and postoperative follow-up. RESULTS: Reduction mammaplasty specimens revealed abnormal findings in 68 (21.5%) patients. High-risk lesions (ADH, ALH, and LCIS) were revealed in 37 (11.7%), and cancer in six (1.9%) patients. Abnormal histopathology correlated with higher age (p = 0.0053), heavier specimen (p = 0.0491), and with no previous breast surgery (p < 0.001). Abnormal histopathological findings were more frequent in patients with reduction mammaplasty performed prior to oncological treatment (p < 0.001), and in patients with immediate reconstruction (p = 0.0064). CONCLUSION: The incidences of malignant and high-risk lesions are doubled compared to patients without prior breast cancer. Patients with abnormal histopathology cannot be preoperatively identified based on demographics. If reduction mammaplasty is performed before oncological treatment, the incidence of abnormal findings is higher. In the light of our results, contralateral reduction mammaplasty with histopathological evaluation in breast cancer patients offers a sophisticated tool to catch those patients whose contralateral breast needs increased attention.

Pretransplant human herpesvirus 6 infection of patients with acute liver failure is a risk factor for posttransplant human herpesvirus 6 infection of the liver.

BACKGROUND: Acute liver failure (ALF) is a significant cause of liver transplantation. We have previously reported that human herpesvirus-6 (HHV-6) was found in most livers of patients with ALF of unknown origin ending up with liver transplantation. In this study, we investigated the posttransplant HHV-6 infection of the liver graft in these patients. METHODS: Thirty-two patients transplanted due to ALF were included in this retrospective study. Twelve of the 15 patients with unknown cause and four of 17 patients with a known cause of ALF had HHV-6 antigens in the explanted liver. Altogether, 18 patients had some pretransplant evidence of HHV-6. After transplantation, the patients were frequently monitored for the viruses, and biopsy histology was performed in every case of graft dysfunction. HHV-6 was demonstrated in liver tissue by immunohistochemistry. RESULTS: During the follow-up of 6 months, hepatic HHV-6 infection was demonstrated in 9 of the 18 patients, at a mean 19 days (6-38 days) after transplantation. All patients with posttransplant HHV-6 showed graft dysfunction. In biopsy histology, seven out of these nine patients demonstrated viral infection, one of them also having CMV antigens in the liver. None of those patients without evidence of pretransplant HHV-6 showed HHV-6 in the posttransplant biopsies. Posttransplant HHV-6 was not treated and the virus had no effect on 1-year patient or graft survivals. CONCLUSION: Pretransplant hepatic HHV-6 infection of patients with ALF is a risk factor for posttransplant HHV-6 infection and liver dysfunction, but has no effect on 1-year graft or patient survival.

Accuracy of axillary staging using sentinel node biopsy or diagnostic axillary lymph node dissection--a case-control study.

We aimed to compare the accuracy of axillary staging in breast cancer between sentinel node biopsy (SNB) and axillary lymph node dissection (ALND). The prevalence of axillary metastases was studied in 166 breast cancer patients with SNB and pair-matched control patients with ALND. The matching factors included age of the patient and grade, histological type and histological size of the tumour. There were 37% of patients with axillary metastases in the SNB group and 31% in the ALND group. Altogether, 57 pairs were discordant in relation to axillary metastases. In 34 discordant pairs the SNB patient and in 23 the ALND patient had axillary metastases, p=ns. Among the 36 discordant pairs with invasive ductal carcinoma (IDC), axillary metastases were detected as often in the SNB and the ALND patients. In the 21 discordant pairs with other histological types, the SNB patient had axillary metastases in 16 pairs and the ALND patient in 5 pairs, p<0.03. SNB seems to be as accurate a method for axillary staging as ALND. However, SNB generated no upstaging effect in IDC, only in other histological tumour types.

Motion restriction and axillary web syndrome after sentinel node biopsy and axillary clearance in breast cancer.

BACKGROUND: We evaluated the prevalence of motion restriction and axillary web syndrome (AWS) after sentinel node biopsy (SNB) and axillary clearance (AC) in a prospective study. AWS is a self-limiting cause of early postoperative morbidity after axillary surgery. Limited range of motion associated with palpable cords of tissue in the axilla are typical for AWS. METHODS: Altogether 85 breast cancer patients who underwent SNB only (49 patients) or SNB and AC (36 patients) were examined before and after surgery. The range of shoulder flexion and abduction and the presence of AWS were registered. RESULTS: The range of shoulder movements was restricted in 24 (45%) patients after SNB only and in 31 (86%) patients who also underwent AC (P = 0.002). AWS was encountered in 10 (20%) patients with SNB and in 26 (72%) with AC (P <0.00005). CONCLUSIONS: In the SNB group, significantly less early postoperative morbidity was observed.

Radio-guided occult lesion localization in patients undergoing breast-conserving surgery and sentinel node biopsy.

BACKGROUND: The objective of the study was to evaluate the feasibility of radio-guided occult lesion localization (ROLL) in breast-conserving surgery for nonpalpable breast cancer. METHODS: Altogether 215 breast cancer patients were included in a prospective study. Ultrasonographically guided intratumoral injection of radioactive tracer was used for tumor localization in 64 patients with nonpalpable tumors, visible in breast ultrasonography (the ROLL group). Nonpalpable tumors, visible only in mammography, were localized with a help of a guidewire in 14 patients (the WGR group). The remaining 137 patients had palpable tumors. RESULTS: The proportion of specimens with close or involved margins (0 to 3 mm) was the same in the ROLL group (6%) and among cases with palpable tumors (5%). In addition the median length of the closest margin did not differ significantly between the groups. CONCLUSIONS: The results of ROLL for nonpalpable breast cancer are comparable with those for resection of palpable tumors.

The impact of radiopharmaceutical particle size on the visualization and identification of sentinel nodes in breast cancer.

OBJECTIVES: The aim of this study was to compare the success rate in lymphatic mapping and sentinel node biopsy in breast cancer using two radiopharmaceuticals. METHODS: The study included 119 breast cancer patients who underwent lymphoscintigraphy after a single intratumoral injection of 99mTc-labelled human albumin colloid with a particle size of 0.2-3 microm (Albu-Res) (large particle group) and 119 pair-matched control patients who underwent lymphoscintigraphy using 99mTc-labelled albumin colloid with a particle size of < 80 nm (Nanocoll) (small particle group). The dose of the tracer was used as the matching factor. RESULTS: Lymphoscintigraphy showed sentinel nodes in the axilla in 101 patients (85%) in the large particle group and in 104 patients (87%) in the small particle group. The mean number of visualized nodes in the axilla was 1.7 in the small particle group and 1.3 in the large particle group (P < 0.05). No radioactive nodes were found in the axilla during the operation in 22 patients (18%) in the small particle group and 11 patients (9%) in the large particle group (P < 0.06). Patients who avoided axillary clearance had a similar number of harvested radioactive nodes irrespective of the particle size of the tracer. CONCLUSIONS: It can be concluded that the success rate in the identification of axillary sentinel nodes may be higher when using the smaller particles, despite the similar visualization rate in lymphoscintigraphy. The number of harvested radioactive nodes was not affected by the particle size of the tracer in patients who avoided axillary clearance.