OBJECTIVE: This study was conducted to evaluate the prognostic significance of the tumor DNA index in patients receiving liver transplantation for hepatocellular carcinoma (HCC) in cirrhosis. BACKGROUND: In patients suffering from HCC in cirrhosis, the current selection for liver transplantation does not optimally achieve the goal to simultaneously maximize the number of viable transplant candidates and reject the smallest number of those who could have benefited. This is the first report on the prognostic significance of the tumor DNA index. PATIENTS AND METHODS: From 1988 to 2007, liver transplantation for HCC in cirrhosis was performed in 246 consecutive patients. The DNA-index was determined by Feulgen staining and semiautomatical image analysis. Interpretation of DNA histograms followed the recommendations outlined in the European Society for Analytical Cellular Pathology consensus report on diagnostic DNA image cytometry. RESULTS: A DNA-index <or=1.5 was detected in the HCC of 159 patients (65%). Five- and 10-year post-transplant survival rates in this group were 86% and 80%, respectively. The DNA-index exceeded 1.5 in 87 patients (35%). These patients had 5- and 10-year survival rates of 27% and 6%, respectively, which were significantly lower than in the DNA-index <or=1.5 group (P < 0.0001). On univariate analysis, DNA-index, vascular invasion, fulfillment of the Milan criteria, and histopathological grading were prognostic parameters. In the multivariate analysis, only DNA-index (odds ratio: 11.9; 95% confidence interval: 7.1-20.0; P < 0.0001) and vascular infiltration (odds ratio: 1.7; 95% confidence interval: 1.1-2.6; P < 0.01) were identified as prognostic variables. CONCLUSION: This is the first study to describe the DNA-index as a strong prognostic indicator after liver transplantation for HCC in cirrhosis. At this time, determination of the DNA-index is likely to be the most promising diagnostic tool in the selection of transplant candidates.

BACKGROUND: EUS-guided FNA (EUS-FNA) is an established tissue-acquisition technique, with most studies concentrating on cytologic analyses of specimens, with only few data existing on histologic assessment. OBJECTIVE: To assess the sensitivity of a combined analysis of histologic followed by cytologic tissue diagnosis. DESIGN: A retrospective 3-center study. METHODS: In consecutive patients undergoing FNA of solid pancreatic masses, core specimens were harvested for histology; residual tissue was examined cytologically. Only unequivocally positive results were regarded as malignant. Criterion standards were positive results from EUS-FNA or other histologic findings, or, if negative, clinical follow-up data (minimum 12 months). RESULTS: Among 192 patients (110 men; mean age 63 years) with mostly pancreatic-head masses (72.4%), overall, adequate tissue was obtained in 98.9% of all cases, with a mean of 1.88 needle passes and an overall sensitivity of 82.9%(95% CI, 76.0%-88.5%). Histology and subsequent cytology provided adequate tissue and sensitivities of 86.5% and 60%, and 92.7% and 68.1%, respectively. Excluding cases with inadequate specimens, sensitivities rose by 4% to 10%. Histology showed a trend for superiority over cytology only in characterizing nonadenocarcinoma tumor types. No differences in sensitivity were found between the centers involved. LIMITATIONS: Retrospective design, different processing of cytologic specimens. CONCLUSIONS: At EUS-FNA in pancreatic masses, combined histologic-cytologic analysis achieved a sensitivity of more than 80%, despite a low number of needle passes and may thus save time. Histology alone did not reach higher sensitivity than cytology. In particular situations, eg, rare tumors, histology may still be required.

OBJECTIVES: Endoscopic ultrasonography (EUS) with the adjunct of EUS-guided fine needle aspiration has become an important diagnostic modality in gastroenterologic oncology. EUS-guided fine needle aspiration mainly relies on cytology; data are scarce that compare cytology and histology. While testing a 22-gauge prototype needle, we prospectively compared the yield for both. METHODS: Forty-two consecutive patients (27 male, 15 female; mean age 59.2 years, range: 17-90 years) were included. In each patient we aimed to make two needle passes, and if the material acquired appeared insufficient macroscopically (no in-room cytopathology was available), further passes were done. The material was sent for cytological and histological assessment. RESULTS: A median number of two passes (range: 2-3) were uneventfully performed for pancreatic lesions (n=30), mediastinal and other lymph nodes/masses (n=8) and various other lesions (n=4) and yielded adequate material for cytology, histology or at least one of the two investigations in 62, 67 and 74% of patients, respectively. No false positive results were found (specificity 100%). Sensitivities were 58.6 and 65.5%, respectively, for cytology and histology alone; combined assessment increased sensitivity to 79.3%. When adjusted values were calculated, based only on those cases with adequate material, sensitivity was 89.5% for cytology and 85.7% for histology, and increased to 100% with combined assessment. CONCLUSION: The new needle achieves sensitivities similar to those previously reported with no significant differences in sensitivity between cytology and histology. More effective tissue acquisition methods must be sought to improve overall results.

Xanthogranulomatous cholecystitis (XGC) is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography (ERC) showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right lobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC.Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.

PURPOSE: To prospectively assess a dose-response relationship for small volumes of liver parenchyma after single-fraction irradiation. METHODS AND MATERIALS: Twenty-five liver metastases were treated by computed tomography (CT)-guided interstitial brachytherapy. Magnetic resonance imaging was performed 1 day before and 3 days and 6, 12, and 24 weeks after therapy. MR sequences included T1-w gradient echo (GRE) enhanced by hepatocyte-targeted gadobenate dimeglumine. All MRI data sets were merged with 3D dosimetry data and evaluated by two radiologists. The reviewers indicated the border of hyperintensity on T2-w images (edema) or hypointensity on T1-w images (loss of hepatocyte function). Based on the total 3D data, a dose-volume histogram was calculated. We estimated the threshold dose for either edema or function loss as the D(90), i.e., the dose achieved in at least 90% of the pseudolesion volume. RESULTS: Between 3 days and 6 weeks, the extension of the edema increased significantly from the 12.9 Gy isosurface to 9.9 Gy (standard deviation [SD], 3.3 and 2.6). No significant change was detected between 6 and 12 weeks. After 24 weeks, the edematous tissue had shrunk significantly to 14.7 Gy (SD, 4.2). Three days postbrachytherapy, the D(90) for hepatocyte function loss reached the 14.9 Gy isosurface (SD, 3.9). At 6 weeks, the respective zone had increased significantly to 9.9 Gy (SD, 2.3). After 12 and 24 weeks, the dysfunction volume had decreased significantly to the 11.9 Gy and 15.2 Gy isosurface, respectively (SD, 3 and 4.1). CONCLUSIONS: The 95% interval from 7.6 to 12.2 Gy found as the minimal hepatocyte tolerance after 6 weeks accounts for the radiobiologic variations found in CT-guided brachytherapy, including heterogeneous dose rates by variable catheter arrays.

BACKGROUND AND AIMS: If temporary inflow occlusion is required during liver resection, the postoperative course might be complicated by ischaemia-reperfusion injury. Steroids protect against ischaemia-reperfusion injury; however, due to its anti-proliferative character concerns exist on its use on liver regeneration after resection. We investigated the effects of methylprednisolone on hepatocyte proliferation after partial hepatectomy with temporary inflow occlusion. PATIENTS AND METHODS: Prior to surgery, one group of Wistar rats received methylprednisolone, while a second group served as non-treated controls. Ischaemia-reperfusion injury was indicated by AST, ALT, and GLDH at 6 h after surgery. Immunohistochemistry tools were used to determine the mitotic index and Ki-67 expression, while cyclin D1 expression characterized the proliferative activity on days 1, 4, 7, and 10. RESULTS: The post-ischaemic liver enzyme release had significantly decreased in the methylprednisolone group, while expression of cyclin D1, percentage of Ki-67-positive cells, and mitotic cell index were comparable in both groups. Similar results were found for bilirubin and albumin and for weight of proliferating liver. CONCLUSION: Although steroid administration significantly reduced ischaemia-reperfusion-associated tissue injury, it has no apparent effects on hepatic regeneration. Thus, steroids could be recommended if a temporary liver ischaemia is required during surgery, in order to reduce complications caused by severe ischaemia-related organ dysfunction.

PURPOSEMETHODS. Intraoperative bone marrow aspiration was done in 26 patients undergoing resection of gastric carcinoma. Peritoneal lavage could not be done in 8 of these 26 patients. The R0-resection rate was 84%( n = 22). A cytokeratin-directed antibody and an antibody directed against carcinoembryonic antigen served for the immunocytochemical detection of tumor cells, and the alkaline phosphatase antialkaline phosphatase method was used for visualization. RESULTS. The bone marrow aspirate and peritoneal lavage fluid were immunocytochemically positive in 31% and 56% of the patients, respectively. There was a trend ( P = 0.10) towards higher overall survival rates in patients with negative bone marrow samples than in those with tumor cells detected in bone marrow samples. Analyzing the results of peritoneal lavage did not reveal any significant differences. In the group of T1/2 cancers, survival was significantly worse if the bone marrow was positive for tumor cells, with 3-year survival rates of 25% vs 77%, respectively ( P < 0.05). CONCLUSION. The rates of tumor cell dissemination into the bone marrow or into the peritoneal cavity were within the scope of previous reports. Dissemination into the bone marrow resulted in significantly impaired survival in patients with T1 and T2 gastric carcinoma, and it did not correlate with known prognostic parameters.There is still much controversy surrounding the prognostic significance of microscopic tumor cell dissemination in gastric cancer and its correlation with histopathologic parameters. We herein investigate such dissemination, predominantly restricted to the subserosa, in patients with gastric cancer.

INTRODUCTION: The clinical value of established prognostic factors seems to be limited since they fail to predict reliably survival of patients after resection of cholangiocarcinoma. DNA ploidy reflecting irregularities of chromosome number and content might be an alternative predictor. In this study, we evaluated the DNA ploidy as a prognostic factor for survival of patients after resection of cholangiocarcinoma. METHODS: This prospective study included 34 patients with cholangiocarcinoma which were surgically resected and followed up to death or more than 3 years. Tissue specimens were taken from the liver tissue immediately after resection and DNA ploidy determined. Survival was related to the type of DNA ploidy as well as to five established prognostic factors. RESULTS: Multivariate analysis revealed that in this study only DNA ploidy (P = 0.012) was significantly associated with prediction of survival. In contrast, neither tumor stage pT (P = 0.073) nor tumor grade pG (P = 0.154), resection margins R (P = 0.322), metastasis M (P = 0.060), lymph node stage pN (P = 0.209), age (P = 0.13) nor sex (P = 0.849) could significantly predict survival. Three-year survival was best for patients with diploid tumors (n = 6) of whom 75% survived more than 3 years. Poor prognostic signs associated with short term survival of less than 18 months were tumors classified as aneuploid (n = 17), large tumors pT4 (n = 8), metastasis pM1 (n = 11), undifferentiated tumors pG3 (n = 9) and non-tumor-free resection margins R2 (n = 14). The best predictor for poor prognosis was aneuploidy since it could identify more patients with a fatal outcome than other prognostic factors. DNA ploidy turned out to discriminate highly significant between diploid, polyploid and aneuploid tumors. DISCUSSION: The most accurate prognostic factor for survival of patients after resection of cholangiocarcinoma was DNA ploidy. Most patients suffering from a diploid tumor turned out to be long term survivors whereas aneuploid tumors indicated a poor prognosis with a rather short survival time of less than 18 months. We conclude that DNA ploidy is a valuable diagnostic tool for identifying subgroups of patients that are at higher risk for tumor progression.

Previous studies reported on both visible and invisible particles in University of Wisconsin (UW) solutions. Those particles originated from components of the bags. In recent clinical observations we noticed macroscopically visible, indissoluble particles in UW bags reaching subzero temperatures during transportation of organs and preservation solutions. In an experimental model we examined whether those particles could be detected following perfusion of abdominal organs with established perfusion solutions. UW-, HTK- or physiological saline solutions reached -3 +/- 0.5 degrees C under conditions frequently applied during transportation. UW solutions demonstrated the accumulation of visible, indissoluble crystals and were subsequently used for the perfusion of abdominal organs in LEW rats. After perfusion with UW solutions stored at freezing temperatures, crystals were detected in all abdominal organs localized in and around vessels, bile ducts, glomeruli and in the interstitium of harvested livers, kidneys and pancreas. By spectroscopy, we were able to characterize crystals as adenosine. A 40-microm pore-size filter eliminated crystals from UW solutions. Crystals were absent in organs perfused with HTK- or saline solutions kept at subzero conditions. UW solutions can reach subzero temperatures under commonly used transportation conditions. Under these conditions, visible crystals accumulate and can be detected in abdominal organs of an experimental system.

BACKGROUND: Renal cell carcinomas (RCCs) are heterogeneous and include several distinct entities with a range of biologic and clinical behaviors from relatively favorable to extremely aggressive. The heterogeneity leads to unpredictable outcome and survival. DNA ploidy is a relatively new predictor differentiating diploid from aneuploid tumor cells according to regular or irregular DNA content. The authors evaluated the predictive value of DNA ploidy in patients who underwent resection because of RCC. METHODS: In a prospective study, 180 patients who underwent resection because of RCC were investigated. DNA cytometry was conducted on each resected tumor to determine DNA ploidy. Patients were completely followed up until death or up to 12 years. RESULTS: Survival analysis showed that patients who underwent resection because of RCC in tumor classifications pT1, pT2, and pT3 survived 10 years in 85%, 53%, and 8% of cases, respectively. Patients suffering from small tumors (pT1 and pT2, n = 44) with diploid nuclei survived 10 years in 94% but only in 8% if the tumor was aneuploid (n = 55). In addition, 91% of patients who underwent resection of large tumors (pT3, n = 12) with diploid nuclei survived 10 years, but no patient with large and aneuploid tumor (n = 51) survived more than 3 years. Furthermore, 92% of all patients afflicted from diploid RCC survived 10 years. This finding was independent of tumor stage. CONCLUSIONS: The results of this study suggest that DNA ploidy is a significant and independent predictor for survival of patients afflicted from RCC and superior to tumor classification and grade. DNA ploidy is a reliable prognostic factor for RCC and yields considerable information for patient management and predicting clinical outcome.