The diagnostic value of cell blocks in Liquid-Based Cytology of bronchial aspiration and bronchial brushing materials.

INTRODUCTION: Fibreoptic bronchoscopy is used for the diagnosis and treatment of several pulmonary diseases. Conventional smear and Liquid-based cytology (LBC) methods are applied to cytology samples of various bronchoscopic techniques. If the cytology sample is sufficient for evaluation, a cell block (CB) can be prepared from the remaining material. The aim of this study is to identify the diagnostic value of conventional smear, LBC and CB methods in bronchial cytological specimens. METHODS: A retrospective review of 329 samples from 240 patients was made and, of these, 144 patients were found to have neoplasia. A blind review of the specimens was performed and all were reclassified individually. The endoscopic findings of the 144 patients with neoplasia were analysed retrospectively. The cytological diagnoses were then compared with the final diagnosis or the endoscopic findings of patients with neoplasia. The sensitivity was calculated for each method, both separately and together. RESULTS: It was determined that CB led to a 10.1% increase in the diagnostic sensitivity for bronchial aspiration (BA) specimens, while no significant increase was seen in bronchial brush specimens. In BA specimens of neoplasia patients with normal bronchoscopic findings, while three methods were applied together with an increase in the number of cases diagnosed as malignant cytology, there was no significant increase in bronchial brush specimens. CONCLUSION: This study demonstrated that adding cell block to CB and LBC seemed to contribute the cytological diagnosis in BA materials significantly. Another advantage of CB is the opportunity of applying advanced methods such as immunocytochemical and molecular techniques.

The effect of blood vessel invasion on prognosis of operated stage I non-small cell lung cancer patients.

OBJECTIVE: A retrospective study was conducted to identify the effect of blood vessel invasion on prognosis in surgically treated stage I non-small cell lung cancer patients. METHODS: A total of 71 consecutive patients who had undergone complete resection for stage I primary non-small cell lung cancer (NSCLC) between 1998 and 2007 were evaluated. All pathological specimens were examined for evidence of blood vessel invasion. The follow-up period was 5-118 months. Survival data were analyzed for all patients using the Kaplan-Meier test. RESULTS: There were 63 men and 8 women (mean age 59.2, age range 35-86). The most common tumor types were adenocarcinoma (35 patients, 49 %) and squamous cell carcinoma (26 patients, 37 %). Twenty-five patients (35 %) had stage IA disease, and 46 had (65 %) stage IB disease. In 13 cases (18 %) blood vessel invasion was demonstrated, whereas in the remaining 58 cases there was no evidence of vascular invasion. Minimum and maximum follow-up periods were 5 and 118 months respectively, with a mean of 41.76 +/- 27 months (median 33.5 months). Overall disease-free survival was 79.6 +/- 6.4 months: 38.3 +/- 12.0 months for the group with blood vessel invasion and 87.5 +/- 6.7 months for the remaining group. The difference between the two groups was statistically significant ( P < 0.003). Overall survival rate was 86.7 +/- 6.7 months: 44.5 +/- 11.3 months for blood vessel invasion group and 98.2 +/- 6.2 months for the remaining group. The difference between the two groups was statistically significant ( P < 0.001). CONCLUSION: Vascular invasion can be an important factor for predicting unfavorable prognosis in stage I NSCLC patients.

The acquisition time of infection: a determinant of the severity of hepatitis C virus-related liver disease in renal transplant patients.

BACKGROUND: The aim of this study was to compare the clinical and histopathological course of HCV infection acquired before and during or after renal transplantation. METHODS: According to HCV status, 197 RT patients were divided into three groups. At the time of RT, anti-HCV antibody was positive in 47 patients (pre-RT HCV group). In 27 patients, in whom anti-HCV negative at the time of RT, anti-HCV and/or HCV RNA was found to be positive following an ALT elevation episode after RT (post-RT HCV group). Both anti-HCV and HCV RNA were negative at all times in remaining 123 patients (control group). RESULTS: Liver biopsy was performed in 31 of 47 patients in pre-RT and 24 of 27 in post-RT HCV group after RT. Duration of follow-up was similar in all groups with a mean of 7.1 +/- 4.0 yr. Ascites and encephalopathy were seen in only post-RT HCV group (22%). Histological grade (6.5 +/- 2.7 vs. 4.1 +/- 1.4) and stage (2.0 +/- 1.5 vs. 0.8 +/- 0.8) was significantly severe in post-RT HCV group (p < 0.01). Three patients died due to liver failure in post-RT HCV group. CONCLUSIONS: HCV infection acquired during or after RT shows a severe and rapidly progressive clinicopathological course, which is significantly different from pre-transplant anti-HCV positive patients.

Intrahepatic cholangiocarcinoma arising in chronic viral hepatitis-associated cirrhosis: two transplant cases.

Hepatitis C virus (HCV) or hepatitis B virus (HBV)-related cirrhosis is known to be a risk factor for hepatocellular carcinoma (HCC). Recently, these viruses have been reported to have an etiologic role in the development of intrahepatic cholangiocarcinoma (ICC). Herein we have reported two cases of HCV- and HBV-related cirrhosis with ICC in whom the pretransplant diagnosis was HCC. The patient with HCV cirrhosis, was a 47-year-old woman with a large nodule in the right lobe. The patient with HBV cirrhosis was a 45-year-old man with two nodules. Serum tumor marker levels, carcinoembryonic antigen (CEA), alphafetoprotein (AFP), and carbohydrate antigen 19-9 (CA 19-9) were determined before live donor liver transplantation (LDLT). The patient with HCV cirrhosis showed mildly elevated serum levels of AFP. The patient with HBV cirrhosis showed an elevated CA 19-9 level. On microscopic examination, all nodules exhibited typical morphological findings of adenocarcinoma. The patient with HCV cirrhosis developed brain metastases 4 years after LDLT. The patient with HBV cirrhosis is disease-free at 18 months after transplantation. In cirrhotic patients with active malignancy who are candidates for LDLT, ICC should be considered in the differential diagnosis. Although the literature is limited, selected patients with ICC may benefit from LDLT.

Association between hepatitis B and hepatocellular carcinoma recurrence in patients undergoing liver transplantation.

BACKGROUND/AIMS: Hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrences affect both patient and graft survivals post-orthotopic liver transplantation (OLT) in HBV patients with HCC. We analyzed the relationship between HBV and HCC recurrence in a large cohort of HBV-OLT patients with versus without HCC. METHODS: Two hundred eighty-seven HBV patients with OLT (72 also with HCC) were included in the study. Mean follow-up in the post-OLT period was 31.7 +/- 24.7 (range, 3-119) months. RESULTS: Post-OLT HBV recurrence observed in 10.1% of patients was more prevalent among the HCC group; 23.6% versus 5.5% in patients with and without HCC, respectively. The mean interval for the development of HBV recurrence was 39.5 +/- 28.5 (range, 2-99) months. Among 72 HCC patients, 8 patients (11.1%) had recurrent HCC, and 7 of them also had HBV recurrence. The mean interval for the development of HCC recurrence was 11.2 +/- 7.85 (range, 2-23) months after OLT. OLT patients with HCC with tumors exceeding the Milan criteria had worse 1-, 3-, and 5-year survival rates than patients with HCC meeting the Milan criteria. HBV and HCC recurrence-free survivals were significantly lower in patients with HCC and HBV recurrence, respectively. In the 7 patients with both HCC and HBV recurrence, mean HBV recurrence time was 9.42 +/- 6.75 months and mean HCC recurrence time was 9.57 +/- 6.75 months. There was a strong correlation between HBV and HCC recurrence times. Cox proportional hazards regression analysis showed that only HCC recurrence was a significant independent predictor of HBV recurrence (P < .001; hazard ratio [HR] = 26.94; 95% confidence interval [CI] = 10.81-67.11). On the other hand, HBV recurrence (P = .013; HR = 5.80; 95% CI = 1.45-23.17) and nodule count (P = .014; HR = 13.08; 95% CI = 1.70-100.83) were significant predictors of HCC recurrence. CONCLUSIONS: HBV and HCC recurrences demonstrate a close relationship in patients with OLT.

Power Doppler US patterns of vascularity and spectral Doppler US parameters in predicting malignancy in thyroid nodules.

AIM: The purpose of this study was to determine whether spectral Doppler ultrasound (US) parameters, including resistive index (RI) and maximal systolic velocity (MSV), or vascular pattern can be used to distinguish malignant from benign thyroid nodules. MATERIALS AND METHODS: We prospectively examined 169 thyroid nodules in 134 patients undergoing sonographically guided fine-needle aspiration biopsy (FNAB). Vascularity as determined by power Doppler US imaging was defined as absent, perinodular alone, or intranodular. For each nodule, the RI and MSV values were recorded as the average of the recordings obtained. Results of the FNAB and surgical pathological examination, if available, were used as a proof of final diagnosis to categorize all nodules as benign or malignant. RESULTS: Seven nodules were excluded from study because of non-diagnostic FNAB results due to hypocellular or insufficient cytological material. Of the remaining nodules, nine were malignant (all confirmed at surgery) and 153 were benign. Of the 145 nodules with intranodular vascularity, nine (6.2%) were malignant and the remaining 136 (93.8%) were benign. The malignant nodules had a mean RI of 0.60 on intranodular and 0.58 on perinodular arteries. These values were not significantly higher than those associated with benign nodules (RI=0.57 and RI=0.56, respectively). Malignant nodules had a mean MSV of 20.4cm/s on intranodular and 35.3cm/s on perinodular arteries that were also not significantly different from those associated with benign nodules (p>0.05). CONCLUSION: The results of this study indicate that Doppler US characteristics including vascular pattern, RI and MSV are not useful parameters for distinguishing malignant from benign thyroid nodules. Therefore, Doppler US characteristics including vascular pattern, RI and MSV values of thyroid nodules can not be used as a diagnostic method to determine which nodules should undergo FNAB.

The incidence and management of acute and chronic rejection after living donor liver transplantation.

Living donor liver transplantation (LDLT) is a good alternative to cadaveric liver transplantation for end-stage liver disease. Herein we report the outcome of 132 LDLTs performed between 1999 and 2005, with special emphasis on the incidence and management of acute and chronic rejection. Among the LDLT population a first acute rejection episode (ARE) was clinically suspected in 24% and proven by liver biopsy in 11%. According to the Banff classification, 50% of AREs were grade 1, and 50%, grade 2. There was no grade 3 AREs. The first ARE occurred between 7 days and 23 months posttransplantation (mean 97 days, median 70 days). Ninety-seven percent (31/32) of the AREs occurred within the first year after transplantation and 3% (1/32) in the second year. Among the patients with ARE, 23% developed a second ARE between 4 and 11 months. A third ARE was detected in 8% of patients after month 18. All AREs responded to adjustment of immunosuppressive doses or steroid boluses. Chronic rejection (CR) was detected in 2%. In conclusion, the incidences of ARE and CR are consistent with the previously reported data. Acute and chronic rejections seem to be mild and easily manageable clinical conditions. Our results also showed a significant difference between clinically suspected and biopsy-proven ARE emphasizing the importance of indicated liver biopsies in the management of the LDLT population.

Hepatocellular carcinoma in children and effect of living-donor liver transplantation on outcome.

Hepatocellular carcinoma (HCC) is primarily observed in the older children and in most cases it develops in association with liver cirrhosis. Liver transplantation offers a good chance for long-term cure. To evaluate the outcome of children with HCC and the impact of living-donor orthotopic liver transplantation (OLT) on survival a retrospective review of radiographic, laboratory, pathologic, and therapeutic data in 13 children (six female and seven male) with chronic liver disease accompanied with HCC were studied. The patients were divided into two groups according to therapeutic modality: transplanted and non-transplanted patients. Kaplan-Meier survival curves in various therapeutic groups were plotted. The mean age of patients was 6.4 +/- 4.8 yr. Pediatric end-stage liver disease score was adapted to model for end-stage liver disease score for HCC and ranged between 1-44 and 18-44, respectively. The underlying liver diseases were tyrosinemia type 1 (n = 6), chronic hepatitis B infection (n = 6), glycogen storage disease type 1 (n = 1). Alfa-feto protein levels were elevated in all patients except one. Median number of tumor nodules was three (1-10), median maximal diameter of tumor nodules was 3.4 cm (0.5-8). Eleven patients were eligible for OLT whereas two patients were not eligible. Seven of the 11 patients considered for transplantation underwent living-donor OLT. Remaining four patients died while waiting on cadaveric transplant list. Overall 1 and 4-yr survival rates for all patients were 53.3 and 26.6%, respectively, and were found significantly higher in transplanted children than non-transplanted children (72%, 72% vs. 33% and 16.6%). No patient had tumor recurrence at median of 36-month follow-up after OLT. OLT is a life-saving procedure for children with chronic liver disease accompanying with HCC. Living-donor OLT avoids the risk of tumor progression and transplant ineligibility in these children.

Liver failure in transplanted liver due to Amanita falloides.

Two patients underwent liver transplantation due to Amanita falloides poisoning. In one of them the clinical symptoms, signs, and laboratory findings related to liver failure were similar to the findings before the transplantation. The patient died and the pathological examination of the liver was similar to the patient's earlier explanted liver.

Primary cardiac lymphoma in a heart transplant recipient.

Posttransplantation lymphoproliferative disease (PTLD) is one of the most serious complications of chronic immunosuppression in transplant recipients. Involvement of the cardiac allograft or development of lymphoma in the heart is extremely rare. We report a primary cardiac lymphoma that developed about 14 months after the operation in a cardiac recipient. The patient presented with vague abdominal complaints. Multiorgan failure developed within a short period of time, and the patient died. The diagnosis of "diffuse large cell lymphoma of B cell type" was made on postmortem examination.

Primary hepatic marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type in a liver transplant patient with hepatitis B cirrhosis.

We describe the clinical, histological, and immunohistochemical features of primary hepatic low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) in a liver transplant recipient with hepatitis B cirrhosis. MALT lymphomas arise in organs normally devoid of lymphoid tissue, which accumulates as a consequence of chronic antigenic stimulation associated with chronic infection or autoimmune disease. Primary hepatic MALT lymphoma is extremely rare; 13 cases have been reported worldwide to date. Our patient is the first case of primary hepatic MALT lymphoma associated with hepatitis B cirrhosis who was treated with orthotopic liver transplantation.

Variations of hepatic veins: helical computerized tomography experience in 100 consecutive living liver donors with emphasis on right lobe.

Anatomical variations in the venous system of liver are not a rarity. A prospective helical computerized tomography (CT) study was undertaken to determine the prevalence of surgically significant hepatic venous anatomic variations among 100 consecutive living liver donors. The studies evaluated the ramification pattern of hepatic veins, the presence of accessory hepatic veins, and of segment 5 or 8 veins (or both) draining into middle hepatic vein. These data obtained by CT influenced surgical planning. Sixty-four donors donated their right lobes and 24 donors, left lateral segments. Only one donor candidate was refused due to combined hepatic and portal venous variations accompanied by multiple bile ducts. Eleven donors were also refused due to reasons other than anatomical variations. Seventeen segment 5 and 17 segment 8 veins draining into middle hepatic vein were anastomosed to inferior vena cava in 23 (36%) of the right lobe liver transplantations. The middle hepatic vein was harvested in only one of the donors. Among the 100 cases, 47 had accessory right inferior hepatic veins, 13 of which were multiple. Twenty-two of the right lobe grafts required surgical anastomoses of these accessory hepatic veins (34%). An isolated hepatic vein anomaly or the presence of accessory hepatic veins are not contraindications to be a living liver donor candidate. However, preoperative knowledge of vascular variations alters surgical management. Helical CT is a valuable tool to delineate the hepatic venous anatomy for surgical planning in living liver donors.

Hepatocellular carcinoma in liver transplant era: a clinicopathologic analysis.

Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, and the prognosis is usually poor. Today, liver transplantation (LT) is a radical but frequently curative treatment modality for HCC. In selected patients, it cures HCC and the underlying cirrhosis at the same time. The present clinicopathological study examined the importance of tumor characteristics for their effects on recurrence and survival rates after LT for HCC. Forty-two native hepatectomy specimens among 250 consecutive orthotopic liver transplantations contained HCC. Patients were predominantly men (30 men, 12 women), ranging in age from 1 to 61 years (median 51). While 20 patients received cadaveric organs, 22 were transplanted from living donors. In 14 patients (33%) HCC presented as a solitary nodule, 5 (12%) as two nodules; 2 (5%) as three nodules; and 21 patients (50%) as more than three nodules. The maximal diameter of the largest tumor not larger than 3 cm in 28 patients (66%), exceeding this size in 14 patients (34%). There was a significant correlation between nodule number and tumor size (r = 0.36, P = 0.05). While 23 patients had no sign of vascular involvement, 17 tumors showed microscopic invasion and two large vessel involvement. There was a positive correlation between vascular invasion and nodule number (r = 0.41, P = 0.05). The histopathological grade of differentiation of the tumors was assessed as "well" in seven patients (14%), moderate in 28 (72%), and poor in 7 (14%). The differentiation was significantly poorer when vascular invasion was observed (r = 0.43, P =.01). According to the TNM classification, 11 patients (26%) were stage I, 6 (14%) stage II, 13 (31%) stage III, and 12 (29%) stage IV. After a median follow-up of 10 months (1-50 months), the overall mortality was 18% (n = 8). Patient survival at 6 month, 1, and 4 years was 88%, 80%, and 60%, respectively. The outcome was significantly poorer for TNM stage IV versus stage I,II, and III tumors to (P =.02). Tumor recurred in three patients at 4,6, and 50 months after liver transplantation. The sites of recurrence were bone, lung, and adrenal glands. In conclusion, liver transplantation represents a safe and feasible treatment for hepatocellular carcinoma with excellent outcomes compared with other treatment modalities. Liver transplantation offers excellent survival rates and chance for cure in stages I, II, and III hepatocellular carcinoma in cirrhotic patients.

Liver transplantation in a patient with Budd-Chiari syndrome secondary to factor V Leiden mutation.

A point mutation in the factor V Leiden gene is the most common hereditary thrombophilic state and an important risk factor for Budd-Chiari syndrome. We report on a patient with Budd-Chiari syndrome secondary to factor V Leiden mutation, who underwent successful liver transplantation. Following liver transplantation, his thrombophilic state was corrected and he did not require anticoagulation therapy. There has been no recurrent venous thrombosis for 14 months after transplantation. Although his activated protein C sensitivity was normal, showing the normalization of protein C-factor V interaction, PCR analysis demonstrated that heterozygosity for factor V Leiden mutation was still present. We suggest checking resistance to activated protein C, rather than PCR analysis of factor V Leiden mutation in patients with Budd-Chiari syndrome after liver transplantation; the presence of the second does not effect clinical outcome.

Histopathologic and Immunophenotypic Features of Childhood and Adult Anaplastic Large-Cell Lymphomas.

The t (2;5) (p23; q35) translocation associated with CD30-positive anaplastic large-cell lymphoma (ALCL) creates a hybrid gene encoding the chimeric nucleolar protein nucleophosmin-anaplastic lymphoma kinase (NFMALK) protein, which can be demonstrated by immunostaining with ALK1 monoclonal antibody. In this study, 40 specimens of ALCL from 6 pediatric, 34 adult patients, were immunostained with monoclonal antibodies against CD30 (Ber-H2), EMA, CD45 (LCA), CD3, CD20 (L26), CD15, and ALK1 antigens, and results were correlated with histopathologic features. The mean age of the pediatric and adult patients was 10-years and 38-years, respectively. ALK1 was positive in 14 cases (35%) representing 83% of pediatric and 26% of adult patients, statistically significantly higher in the pediatric group (p= 0.01). Considering the better prognosis attributed to cases with t (2;5), it is interesting to note that the percentage of ALK1-positive cases is significantly higher in pediatric patients with coexpression of EMA, compared to adults.