Calculation of protein requirements; a comparison of calculations based on bodyweight and fat free mass.

BACKGROUND & AIMS: In dietary practice, it is common to estimate protein requirements on actual bodyweight, but corrected bodyweight (in cases with BMI <20 kg/m2 and BMI ≥30 kg/m2) and fat free mass (FFM) are also used. Large differences on individual level are noticed in protein requirements using these different approaches. To continue this discussion, the answer is sought in a large population to the following question: Will choosing actual bodyweight, corrected bodyweight or FFM to calculate protein requirements result in clinically relevant differences? METHODS: This retrospective database study, used data from healthy persons ≥55 years of age and in- and outpatients ≥18 years of age. FFM was measured by air displacement plethysmography technology or bioelectrical impedance analysis. Protein requirements were calculated as 1) 1.2 g (g) per kilogram (kg) actual bodyweight or 2) corrected bodyweight or 3) 1.5 g per kg FFM. To compare these three approaches, the approach in which protein requirement is based on FFM, was used as reference method. Bland-Altman plots with limits of agreement were used to determine differences, analyses were performed for both populations separately and stratified by BMI category and gender. RESULTS: In total 2291 subjects were included. In the population with relatively healthy persons (n = 506, ≥55 years of age) mean weight is 86.5 ± 18.2 kg, FFM is 51 ± 12 kg and in the population with adult in- and outpatients (n = 1785, ≥18 years of age) mean weight is 72.5 ± 18.4 kg, FFM is 51 ± 11 kg. Clinically relevant differences were found in protein requirement between actual bodyweight and FFM in most of the participants with overweight, obesity or severe obesity (78-100%). Using corrected bodyweight, an overestimation in 48-92% of the participants with underweight, healthy weight and overweight is found. Only in the Amsterdam UMC population, protein requirement is underestimated when using the approach of corrected bodyweight in participants with severe obesity. CONCLUSION: The three approaches in estimation of protein requirement show large differences. In the majority of the population protein requirement based on FFM is lower compared to actual or corrected bodyweight. Correction of bodyweight reduces the differences, but remain unacceptably large. It is yet unknown which method is the best for estimation of protein requirement. Since differences vary by gender due to differences in body composition, it seems more accurate to estimate protein requirement based on FFM. Therefore, we would like to advocate for more frequent measurement of FFM to determine protein requirements, especially when a deviating body composition is to be expected, for instance in elderly and persons with overweight, obesity or severe obesity.

Clinical outcomes of chronic hepatitis C patients related to baseline liver fibrosis stage: a hospital-based linkage study.

BACKGROUND AND AIMS: Rates of long-term clinical outcomes of chronic hepatitis C in patients with none, mild or severe liver fibrosis are required to determine benefits of anti-viral therapies. This study evaluated long-term outcomes for chronic hepatitis C stratified by all Metavir fibrosis stages. METHODS: Clinical outcomes were determined using population-based data linkage methodology for 880 hepatitis C patients who had a liver biopsy performed from 1992 to 2012. RESULTS: During 9386 person-years of follow up, 28 patients developed hepatocellular carcinoma, 58 developed liver decompensation and 122 died or underwent liver transplantation. There was no significant difference in liver-related death for those with F0-F2 with an 18-year survival probability >94%. Hazard ratio of liver-related death for F3 compared with F0-F2 was 4.24 (P = 0.003), with no significant difference in the first 13-year follow up. The 15-year decompensation-free survival for F0, F1 and F2 was 100%, 96% and 94% respectively and for hepatocellular carcinoma-free survival was 100%, 99% and 98%. Hazard ratio of liver complication (hepatocellular carcinoma or decompensation)-free survival for F3 compared with F0-F2 was 3.22 (P = 0.001), with no significant difference during the first 7-year follow up. F4 had significantly higher risk of liver-related death, decompensation and hepatocellular carcinoma than F3 (P < 0.001). CONCLUSIONS: Chronic hepatitis C patients with F2 or less had few liver complications after 15 years. For F3 patients, the significant increase in liver-related death occurred after 13 years and for liver complications after 7 years.

Standardised reporting protocol for endoscopic resection for Barrett oesophagus associated neoplasia: expert consensus recommendations.

Endoscopic resection (ER) is considered the therapy of choice for intraepithelial neoplasia associated with visible lesions and T1a adenocarcinoma. Pathologists are bound to encounter specimens collected via these techniques more frequently in their practice. A standardised protocol for handling, grossing, and assessing ER specimens should be adopted to ensure that all prognostic information and characteristics influencing treatment are included in reports (see Supplementary Video Abstract, http://links.lww.com/PAT/A22). The entire specimen should be appropriately oriented, processed and assessed. An ER specimen will commonly show intraepithelial neoplasia or invasive carcinoma. There are essential features that should be recorded if invasive carcinoma is found as they dictate further management and follow-up. These features are the margin status, depth of invasion, degree of differentiation and presence or absence of lymphovascular invasion. Important features such as duplication of muscularis mucosae should be recognised to avoid misinterpretation of depth of invasion. Key diagnostic and prognostic elements that are essential for optimal clinical decisions have been included in the reporting format proposed by the Structured Pathology Reporting committee of the Royal College of Pathologists of Australasia (RCPA).

Comparison of noninvasive models of fibrosis in chronic hepatitis B.

BACKGROUND AND GOALS: Liver fibrosis influences treatment and surveillance strategies in chronic hepatitis B (CHB). This multicenter study aimed to examine the accuracy of serum fibrosis models in CHB patients including those with low alanine aminotransferase (ALT) levels and serially in those undergoing treatment. METHOD: We examined noninvasive fibrosis models [Hepascore, Fibrotest, APRI, hepatitis e antigen (HBeAg)-positive and -negative models] in 179 CHB patients who underwent liver biopsy and fibrosis assessment by METAVIR and image morphometry. Serial Hepascore measurements were assessed in 40 subjects for up to 8.7 years. RESULTS: Hepascore was more accurate than Fibrotest [area under the curve (AUC) 0.83 vs. 0.72, P = 0.05] and HBeAg-positive model (AUC 0.83 vs. 72, P = 0.03) for significant fibrosis but was not significantly different to APRI or HBeAg-negative scores. Fibrosis area assessed by morphometry was correlated with Hepascore (r = 0.603, P < 0.001), Fibrotest (r = 0.392, P = 0.03), and HBeAg-positive (r = 0.492, P = 0.001) scores only. Among 73 patients with an ALT <60 IU/L, noninvasive models were useful to predict fibrosis (PPV 80-90%) or exclude significant fibrosis (NPV 79-100%). Hepascore increased significantly among patients monitored without treatment and reduced among patients undergoing therapy (0.05/year ± 0.03 vs. -0.04/year ± 0.02, P = 0.007). CONCLUSIONS: Serum fibrosis models are predictive of fibrosis in CHB and assist in identifying subjects with low-normal ALT levels for treatment.

Urgent liver transplantation for acute liver failure due to parvovirus B19 infection complicated by primary Epstein-Barr virus and cytomegalovirus infections and aplastic anaemia.

An 11-year-old boy presented with hepatic failure secondary to parvovirus B19 infection, requiring urgent liver transplantation. His recovery was complicated by primary Epstein-Barr virus and cytomegalovirus infections. He subsequently developed aplastic anaemia that has been refractory to antithymocyte globulin and cyclosporine therapy and may now require bone marrow transplantation. We present this case to emphasize parvovirus as a rare cause of hepatic failure and of aplastic anaemia as a complication of the virus.

Comparative prevalences of Brachyspira aalborgi and Brachyspira (Serpulina) pilosicoli as etiologic agents of histologically identified intestinal spirochetosis in Australia.

DNA from gastrointestinal biopsy specimens from 28 Australian patients with histologic evidence of intestinal spirochetosis (IS) was subjected to PCRs to amplify segments of the 16S rRNA and NADH oxidase genes of Brachyspira aalborgi and Brachyspira (Serpulina) pilosicoli. B. aalborgi was identified in specimens from 24 (85.7%) patients and B. pilosicoli in those from 4 (14.3%) patients (2 of whom were also positive for B. aalborgi). For two patients, no product was amplified. This study demonstrates that B. aalborgi is much more commonly involved in histologically identified IS in Australian patients than is B. pilosicoli. This is the first report of amplification of B. pilosicoli DNA from humans with IS.

Can CD34 discriminate between benign and malignant hepatocytic lesions in fine-needle aspirates and thin core biopsies?

BACKGROUND: Distinguishing well differentiated hepatocellular carcinoma (HCC) from benign hepatocellular lesions is a well recognized problem in fine-needle aspiration (FNA) cytology. The endothelial cell marker CD34 is negative in normal hepatic sinusoids and stains vessels diffusely in HCC. This feature is useful in distinguishing benign from malignant hepatocytic lesions in histological specimens, although benign lesions may show focal positivity for CD34 confined to periportal and periseptal areas. In this study, we assess the role of CD34 in cell block and thin core biopsy material from benign and malignant hepatocellular lesions, and compare it with reticulin staining. METHODS: Cell blocks and thin core biopsies were assessed from 40 cases of HCC and 25 benign hepatocytic lesions. HCCs were scored for nuclear grade. Sections were stained for CD34 antigen and scored semi-quantitatively. Previously performed reticulin stains were reviewed. RESULTS: Thirty three of 40 HCCs (82.5%) showed diffuse positivity for CD34. The other seven cases showed either focal positivity (four cases), minimal positivity (two cases) or negative staining (one case). These results did not correlate with the nuclear grade of the tumor. Two of 25 benign cases (8%) showed diffuse positivity for CD34, 8 showed focal positivity, 11 showed minimal positivity, and 4 showed negative staining. All HCCs showed an abnormal reticulin pattern characterized by expanded trabeculae and islands, or sheets, with decreased or absent reticulin. All of the benign hepatocellular lesions showed a normal trabecular reticulin pattern. CONCLUSIONS: Diffusely positive CD34 staining is useful to support a diagnosis of well differentiated HCC, but in our study the reticulin stain distinguished more consistently between benign and malignant lesions.

Cytodiagnosis of well differentiated hepatocellular carcinoma: can indeterminate diagnoses be reduced?

BACKGROUND: Distinction of well differentiated hepatocellular carcinoma (HCC) from benign hepatocellular lesions is a well recognized problem in fine-needle aspiration (FNA) cytology, sometimes leading to indeterminate reports. The aim of this study was to critically examine criteria that might allow definitive diagnosis in these cases. METHODS: FNA smears and cell blocks from 65 patients with primary hepatocellular lesions were reviewed. Seventy separate samples had been obtained. The initial reports in these samples were: HCC in 34, benign findings in 27, and indeterminate findings in 9. We defined architectural and cytological features seen in the malignant cases but not seen in the benign cases, including an assessment of reticulin in cell blocks. These criteria were then applied to the indeterminate cases. RESULTS: The most specific cytologic criteria of malignancy in well differentiated HCC were (i) numerous stripped atypical nuclei, (ii) macronucleoli, (iii) increased mitoses, and (iv) multinucleation. The most specific architectural criteria in smears were (i) widened trabeculae, (ii) well defined capillaries traversing tissue fragments, and (iii) solid islands of hepatocytes rimmed by endothelial cells. The most valuable architectural criteria in cell blocks were (i) trabeculae greater than two cells thick and (ii) reduced or absent reticulin framework. Using the above criteria a retrospective diagnosis of HCC was possible in eight of the nine indeterminate cases, all but one of which have subsequently been confirmed as malignant. CONCLUSIONS: Close attention to architectural features in both smears and cell blocks should allow most well differentiated HCCs to be diagnosed by FNA cytology. A reticulin stain should be part of the routine assessment of cell blocks. Cancer (Cancer Cytopathol)

Banff schema for grading liver allograft rejection: utility in clinical practice.

An accurate and functional system for grading acute liver allograft rejection is important for patient management, research, and communication. The Banff schema is a consensus document designed to provide an internationally accepted standard for this purpose. The aim of this study is to determine if application of the Banff schema would significantly alter the grading of acute liver allograft rejection compared with the Birmingham system. One hundred twenty-four post-liver transplantation biopsies performed by the Western Australian Liver Transplantation Service between 1992 and 1997 were retrospectively analyzed by a pathologist and a hepatologist. Each was supplied with a brief clinical history before applying the Banff and Birmingham criteria. Results were compared with each other and to the diagnosis made at the time of the biopsy, which was based on the European grading system. Rejection was diagnosed by the reviewers in 61 of 124 biopsy specimens according to the criteria of Snover. The Banff schema and Birmingham system agreed on the grade of rejection in 22 of the 61 biopsy specimens. The Banff schema elevated the grade of rejection in 39 specimens by an increment of one. In no instance did the Banff schema reduce the grade. Comparison between the Banff schema and diagnosis made at the time of biopsy showed agreement in 39 specimens, whereas the Banff schema elevated the grade in 15 specimens and reduced the grade in 23 specimens. In comparison to the Birmingham system, the Banff schema elevated the grade of liver allograft rejection in the majority of biopsy specimens, and this has the potential to alter clinical management with the adoption of the Banff schema or if the systems are used interchangeably.

PCR amplification from fixed tissue indicates frequent involvement of Brachyspira aalborgi in human intestinal spirochetosis.

PCR procedures amplifying portions of the 16S rRNA and NADH oxidase genes of Brachyspira aalborgi and Serpulina pilosicoli were applied to DNA extracted from paraffin-embedded human colonic or rectal tissues from 30 Norwegian, Australian, and U.S. patients, 16 of whom had histologic evidence of intestinal spirochetosis (IS). B. aalborgi-specific sequences were identified by PCR in 10 of the IS patients (62.5%) but none of the others, while S. pilosicoli sequences were not detected in tissues from any patient. Direct sequencing of products from three of the positive samples provided further confirmation of the presence of B. aalborgi. B. aalborgi may be a more common cause of intestinal spirochetosis than has been previously thought.

Magnetic resonance features of focal nodular hyperplasia of the liver.

The magnetic resonance imaging (MRI) features of 11 biopsy-proven lesions of focal nodular hyperplasia (FNH) of the liver were reviewed retrospectively. Only three lesions showed atypical features. It is believed MRI can reliably differentiate FNH from other liver tumours when strict criteria are fulfilled.

Rectal washout eliminates exfoliated malignant cells.

PURPOSE: Irrigation of the rectal stump before anastomosis after resection for carcinoma is accepted colorectal surgical practice. However, not all surgeons perform this routinely, and it has never been established conclusively that irrigation of the rectal stump eliminates exfoliated malignant cells or even reduces local recurrence. The patients of a surgeon whose standard surgical practice involved rectal irrigation were compared with those of a surgeon who does not routinely practice rectal irrigation. METHOD: Ten patients were given rectal washout with 200 to 500 ml of normal saline introduced via a Foley catheter per rectum. Ten patients were not given rectal washout. In both groups the anastomosis was performed with a circular stapler, and the stapler and donuts were rinsed in 200 ml of normal saline. The saline was sent for cytologic examination and classified as malignant cells seen or no malignant cells seen. The cytopathologist was blinded to the washout status. RESULTS: Of the ten patients who had rectal washout performed, none had malignant cells seen. Of the ten patients who did not have rectal washout performed, eight had malignant cells seen in the cytology (P = 0.007; two-tailed Fisher's exact probability test). CONCLUSION: Rectal washout eliminates exfoliated malignant cells in the rectum in the vicinity of the anastomosis.

Medullary carcinoma of the thyroid: accuracy of diagnosis of fine-needle aspiration cytology.

BACKGROUND: A preoperative diagnosis of medullary carcinoma of the thyroid (MCT) allows for the investigation of associated multiple endocrine neoplasia/ pheochromocytoma, and definitive surgery without the need for frozen section. Criteria for cytodiagnosis are well known but variable patterns of presentation may cause diagnostic difficulty. METHODS: This study examines the accuracy of cytodiagnosis and the value of ancillary tests in 17 patients seen between 1976 and 1997. Nine patients underwent thyroid gland aspirations, five patients underwent fine-needle aspiration (FNA) of the thyroid and cervical lymph nodes, and three patients underwent cervical lymph node aspiration alone. Electron microscopy (EM) of aspirated material was performed in nine cases and immunocytochemistry in two cases. RESULTS: In all cases the diagnosis was suggested by FNA. In four cases, diagnosis and management were based on cytology alone. EM of FNA material was confirmatory in nine cases, two of which also showed positive calcitonin immunocytochemistry. In three cases the diagnosis was not proven until surgical resection, and in one case FNA confirmed lymph node metastasis in known MCT. Frozen section in five patients did not change the level of diagnostic confidence over the FNA diagnosis in any case. In four other thyroid tumors (one Hürthle cell follicular carcinoma, two anaplastic carcinomas, and one hyperplastic nodule) MCT was suspected in the FNA differential diagnosis but later excluded. In the Hürthle cell tumor immunoperoxidase staining was positive for calcitonin and in one anaplastic carcinoma, a neuroendocrine phenotype was suggested. In the latter case, additional EM excluded MCT. CONCLUSIONS: Although correct diagnosis is made by cytology in the majority of instances, other tumors may show cytologic findings similar to MCT. EM of FNA material was found to be the most definitive method of proving or excluding MCT. Immunocytochemistry may be misleading for rarely performed tests.

Microsatellite instability and loss of heterozygosity in mammary carcinoma and its probable precursors.

Microsatellite instability is a form of genetic damage that may be due to defective mismatch repair genes and may be a marker of processes leading to malignancy. We have analysed a series of epithelial hyperplasia of usual type, carcinomas in situ and invasive and metastatic carcinomas from the mammary gland on the assumption that they represent stages in the evolution of mammary carcinoma. Eight markers on chromosomes 3p, 4q, 9p, 11p, 14q, 17p, 17q and Xq were examined for microsatellite instability and loss of heterozygosity. High rates of loss on chromosomes 17p, 17q and Xq indicate that these chromosomal arms contain genes important in mammary carcinogenesis. The rate of microsatellite instability observed in this study was uniformly low, irrespective of the lesion. This implies that microsatellite instability is not a marker of malignancy in most instances of mammary neoplasia.

Chronic liver disease in asymptomatic hepatitis C antibody positive blood donors.

The risks of acquisition of hepatitis C infection, the histological spectrum of liver disease, and the presence of viraemia were investigated in anti-hepatitis C virus (HCV) antibody positive blood donors. All 357 (0.64%) blood donors to the South Australian Red Cross Transfusion Service found to have anti-HCV antibody during the first seven months of testing in 1990 were assessed, and 70 (19.6%) were found to have elevated alanine transaminase levels. These subjects were referred for participation in the study; 31 presented for enrollment. Sixteen (52%) of the 31 patients had previously used intravenous drugs, four (13%) had been transfused, two (6%) had a history of occupational exposure to blood, and three (10%) had tattoos and ear-piercing as possible risk factors for acquisition of hepatitis C. There was no history of parenteral exposure in six (16%). None of these donors had clinical evidence of liver disease, but in all 24 of the 31 who had a liver biopsy there was histological evidence of significant liver damage. Twelve had evidence of chronic active hepatitis. All 24 subjects biopsied were viraemic as judged by the presence of HCV RNA in serum.