Digital image analysis of Ki67 hotspot detection and index counting in gastroenteropancreatic neuroendocrine neoplasms.

The Ki-67 proliferative index plays a pivotal role in the subclassification of neuroendocrine neoplasm (NEN) according to the WHO Classification of Digestive System Tumors (5th edition), which designates neuroendocrine tumor (NET) grades 1, 2, and 3 for Ki-67 proliferative index of <3 %, 3-20 %, and >20 %, respectively. Proliferative index calculation must be performed in the hotspot, traditionally selected by visual scanning at low-power magnification. Recently, gradient map visualization has emerged as a tool for various purposes, including hotspot selection. This study includes 97 cases of gastrointestinal neuroendocrine neoplasms, with hotspots selected by bare eye and gradient map visualization (GM). Each hotspot was analyzed using three methods: eye estimation (EE), digital image analysis (DIA), and manual counting. Of the NENs studied, 91 % were NETs (26 % for G1, 55 % for G2, and 10 % for G3). Only 9 cases were neuroendocrine carcinoma (NEC). Between two hotspot selection methods, GM resulted in a higher grade in 14.77 % of cases, primarily upgrading from NET G1 to G2. Among the counting methods, DIA demonstrated substantial agreement with manual counting, both for pathologist and resident. Grading by other methods tended to result in a higher grade than MC (26.99 % with EE and 8.52 % with DIA). Given its clinical and statistical significance, this study advocates for the application of GM in hotspot selection to identify higher-grade tumors. Furthermore, DIA provides accurate grading, offering time efficiency over MC.

High-Throughput, Machine Learning-Based Quantification of Steatosis, Inflammation, Ballooning, and Fibrosis in Biopsies From Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Liver biopsy is the reference standard for staging and grading nonalcoholic fatty liver disease (NAFLD), but histologic scoring systems are semiquantitative with marked interobserver and intraobserver variation. We used machine learning to develop fully automated software for quantification of steatosis, inflammation, ballooning, and fibrosis in biopsy specimens from patients with NAFLD and validated the technology in a separate group of patients. METHODS: We collected data from 246 consecutive patients with biopsy-proven NAFLD and followed up in London from January 2010 through December 2016. Biopsy specimens from the first 100 patients were used to derive the algorithm and biopsy specimens from the following 146 were used to validate it. Biopsy specimens were scored independently by pathologists using the Nonalcoholic Steatohepatitis Clinical Research Network criteria and digitalized. Areas of steatosis, inflammation, ballooning, and fibrosis were annotated on biopsy specimens by 2 hepatobiliary histopathologists to facilitate machine learning. Images of biopsies from the derivation and validation sets then were analyzed by the algorithm to compute percentages of fat, inflammation, ballooning, and fibrosis, as well as the collagen proportionate area, and compared with findings from pathologists' manual annotations and conventional scoring systems. RESULTS: In the derivation group, results from manual annotation and the software had an interclass correlation coefficient (ICC) of 0.97 for steatosis (95% CI, 0.95-0.99; P < .001); ICC of 0.96 for inflammation (95% CI, 0.9-0.98; P < .001); ICC of 0.94 for ballooning (95% CI, 0.87-0.98; P < .001); and ICC of 0.92 for fibrosis (95% CI, 0.88-0.96; P = .001). Percentages of fat, inflammation, ballooning, and the collagen proportionate area from the derivation group were confirmed in the validation cohort. The software identified histologic features of NAFLD with levels of interobserver and intraobserver agreement ranging from 0.95 to 0.99; this value was higher than that of semiquantitative scoring systems, which ranged from 0.58 to 0.88. In a subgroup of paired liver biopsy specimens, quantitative analysis was more sensitive in detecting differences compared with the nonalcoholic steatohepatitis Clinical Research Network scoring system. CONCLUSIONS: We used machine learning to develop software to rapidly and objectively analyze liver biopsy specimens for histologic features of NAFLD. The results from the software correlate with those from histopathologists, with high levels of interobserver and intraobserver agreement. Findings were validated in a separate group of patients. This tool might be used for objective assessment of response to therapy for NAFLD in practice and clinical trials.

Late allograft fibrosis in pediatric liver transplant recipients: Assessed by histology and transient elastography.

Late allograft fibrosis in LT recipients can cause graft dysfunction and may result in re-transplantation. TE is a non-invasive tool for the assessment of liver fibrosis. We aimed to evaluate the prevalence of allograft fibrosis in pediatric LT recipients, identify factors associated with allograft fibrosis, and determine the diagnostic value of TE, compared to histology. All children who underwent LT for ≥3 years were included. TE was performed for LSM in all patients. LSM of ≥7.5 kPa was considered as abnormal and suggestive of allograft fibrosis. Percutaneous liver biopsy was performed when patients had abnormal LSM and/or abnormal LFTs. Histological fibrosis was diagnosed when METAVIR score ≥F1 or LAF scores ≥1. TE was performed in 43 patients and 14 (32.5%) had abnormal LSM suggestive of allograft fibrosis. Histological fibrosis was identified in 10 of the 15 patients (66.7%) who underwent percutaneous liver biopsy and associated findings included chronic active HBV infection (n = 3), and late acute rejection (n = 3). Multivariate analysis showed that graft age was significantly associated with allograft fibrosis (OR = 1.22, 95% CI: 1.05-1.41, P = 0.01). In conclusion, late allograft fibrosis is common in children undergoing LT for ≥3 years and associated with graft age. HBV infection and late acute rejection are common associated findings. Abnormal TE and/or LFTs may guide physicians to consider liver biopsy for the detection of late allograft fibrosis in LT children.

BRAF V600E mutation in biliary proliferations associated with α1 -antitrypsin deficiency.

AIMS: Both homozygous and heterozygous α1 -antitrypsin (AAT) deficiency patients are at risk of developing hepatocellular carcinoma (HCC), but also of developing cholangiocarcinoma and combined HCC and cholangiocarcinoma. The aim of our study is to report a series of bile duct adenomas (BDAs) and intrahepatic cholangiocarcinoma (ICCs) in adult AAT deficiency patients, observed in our institution over a 5-year period. Our observational study includes a detailed investigation of their immunohistochemical profile and BRAF V600E mutation status. METHODS AND RESULTS: Eleven biliary lesions from five AAT deficiency patients (six BDAs from three cirrhotic patients with other concurrent liver diseases; three BDAs and two ICCs from two non-cirrhotic patients) were identified between 2010 and 2015 during routine histological investigation. Most BDAs expressed CD56, EpCAM, CD133, and CA19-9, similarly to hepatic progenitor cells (HPCs), and carried the BRAF V600E mutation (87.5%). One ICC showed a similar immunohistochemical profile but no evidence of the BRAF V600E mutation. CONCLUSIONS: Most of the biliary proliferations in AAT deficiency patients have an appearance of BDA with an HPC-related immunohistochemical profile. Their frequent BRAF V600E mutations support their neoplastic nature, but not necessarily their progression to ICC. We believe that this may depend on the patient genotype, or require a different pathway or a second mutational hit for malignant transformation. We postulate that BDA represents a heterogeneous group of biliary lesions, and that those associated with AAT deficiency may constitute a group of their own.

Henoch-Schönlein without Purpura: A Case Report and Review Literature.

Henoch-Schönlein purpura (HSP) is a multi-organ vasculitis involving skin, joints, gastrointestinal tract, and kidneys. The present study reported a 5-year-old boy presenting with intense abdominal pain, bloody diarrhea, and protein-losing enteropathy. Investigations for infectious enteritis were negative. Esophagogastroduodenoscopy showed swelling and erythematous mucosa with hemorrhagic spots at duodenal bulb to the third part of duodenum. Histopathology of endoscopic biopsies revealed non-specific duodenitis. HSP was suspected, based on duodenitis and the presence of inflammatory markers without identifiable causes. Corticosteroid was started resulting in marked improvement of his clinical symptoms. Two weeks later, he developed nephrotic-range proteinuria, thus kidney biopsy was performed. Renal histology was consistent with IgA nephropathy, supporting the diagnosis of HSP This report emphasizes that patients with HSP may not always show visible purpura, and the diagnosis requires a high index of suspicion. GI endoscopy and renal biopsy may be helpful for the diagnosis in selected patients presenting with atypical presentations.

Correlation between magnetic resonance imaging proton density fat fraction (MRI-PDFF) and liver biopsy to assess hepatic steatosis in obesity.

Obesity is highly associated with Non-alcoholic fatty liver disease (NAFLD) and increased risk of liver cirrhosis and liver cancer-related death. We determined the diagnostic performance of the complex-based chemical shift technique MRI-PDFF for quantifying liver fat and its correlation with histopathologic findings in an obese population within 24 h before bariatric surgery. This was a prospective, cross-sectional, Institutional Review Board-approved study of PDFF-MRI of the liver and MRI-DIXON image volume before bariatric surgery. Liver tissues were obtained during bariatric surgery. The prevalence of NAFLD in the investigated cohort was as high as 94%. Histologic hepatic steatosis grades 0, 1, 2, and 3 were observed in 3 (6%), 25 (50%), 14 (28%), and 8 (16%) of 50 obese patients, respectively. The mean percentages of MRI-PDFF from the anterior and posterior right hepatic lobe and left lobe vs. isolate left hepatic lobe were 15.6% (standard deviation [SD], 9.28%) vs. 16.29% (SD, 9.25%). There was a strong correlation between the percentage of steatotic hepatocytes and MRI-PDFF in the left hepatic lobe (r = 0.82, p < 0.001) and the mean value (r = 0.78, p < 0.001). There was a strong correlation between MRI-derived subcutaneous adipose tissue volume and total body fat mass by dual-energy X-ray absorptiometry, especially at the L2-3 and L4 level (r = 0.85, p < 0.001). MRI-PDFF showed good performance in assessing hepatic steatosis and was an excellent noninvasive technique for monitoring hepatic steatosis in an obese population.

Detection of centroblast cells in H&E stained whole slide image based on object detection.

Introduction: Detection and counting of Centroblast cells (CB) in hematoxylin & eosin (H&E) stained whole slide image (WSI) is an important workflow in grading Lymphoma. Each high power field (HPF) patch of a WSI is inspected for the number of CB cells and compared with the World Health Organization (WHO) guideline that organizes lymphoma into 3 grades. Spotting and counting CBs is time-consuming and labor intensive. Moreover, there is often disagreement between different readers, and even a single reader may not be able to perform consistently due to many factors. Method: We propose an artificial intelligence system that can scan patches from a WSI and detect CBs automatically. The AI system works on the principle of object detection, where the CB is the single class of object of interest. We trained the AI model on 1,669 example instances of CBs that originate from WSI of 5 different patients. The data was split 80%/20% for training and validation respectively. Result: The best performance was from YOLOv5x6 model that used the preprocessed CB dataset achieved precision of 0.808, recall of 0.776, mAP at 0.5 IoU of 0.800 and overall mAP of 0.647. Discussion: The results show that centroblast cells can be detected in WSI with relatively high precision and recall.

Neuroendocrine carcinomas of the uterine cervix: A clinicopathological study.

BACKGROUND: Neuroendocrine carcinoma (NEC) is a rare entity of uterine cervical carcinoma. Most of them have a more aggressive course and worse prognosis than a common type squamous cell carcinoma. Therefore, precise diagnosis is very crucial. OBJECTIVE: To study clinicopathological correlation and immunohistochemistry of uterine cervical NEC MATERIAL AND METHOD: All primary uterine cervical carcinomas from a 51-month period were histopathologically reviewed. Suspicious NECs were retrieved and immunohistochemically studiedfor chromogranin, synaptophysin, non-specific esterase (NSE) and CD56. Clinical information including treatments and mean disease free survival time were obtainedfrom chart review RESULTS: Fourteen (3.5%) cases of NEC were identified from 389primary uterine cervical carcinomas between October 1, 2002 and December 31, 2006 and classified into small cell neuroendocrine carcinoma (SNEC, 8 cases), large cell neuroendocrine carcinoma (LNEC, 3 cases), mixed SNEC and adenocarcinoma (2 cases), and mixed SNEC anid squamous cell carcinoma (1 case). All NEC presented with abnormal vaginal bleeding. The median age was 44 years (34-75 years). Exophytic mass was noted in 11 patients (78.6%). Five patients (36%) had distant metastases. All cases were immunoreactive for at least two neuroendocrine markers. Nine cases (64.3%) were positive for chromogranin, 11 (78.6%) for synaptophysin, 12 (85. 7%) for NSE, and 11 (78.6%) for CD56. CD56 was positive in eight of 11 SNEC cases. The mean disease free interval and overall survival time were 17.5 and 23.9 months, respectively CONCLUSION: Neuroendocrine carcinoma of the cervix is rare and has poor prognosis. In addition to histopathology, panel ofimmunohistochemistry is mandatory in the diagnosis of neuroendocrine carcinoma. Varying results of immunohistochemistry may be found.

Performance of Cytomegalovirus Real-Time Polymerase Chain Reaction Assays of Fecal and Plasma Specimens for Diagnosing Cytomegalovirus Colitis.

INTRODUCTION: Cytomegalovirus (CMV) viral load detected by real-time polymerase chain reaction (PCR) in plasma or stool may facilitate detection of CMV colitis. METHODS: This prospective study enrolled 117 patients with clinically suspected CMV colitis. Patients presenting with gastrointestinal symptoms and having increased risk of CMV infection were eligible. All participants underwent colonoscopy with tissue biopsy. Five patients underwent colonoscopy twice because of clinical recurrence, resulting in a total of 122 colonoscopies. Stool CMV-PCR and plasma CMV-PCR were performed within 7 days before/after colonoscopy. Twenty asymptomatic volunteers also underwent the same protocol. RESULTS: Twenty-seven (23.1%) of 122 colonoscopies yielded positive for CMV colitis. The sensitivity and specificity was 70.4% and 91.6% for stool CMV-PCR and 66.7% and 94.7% for plasma CMV-PCR, respectively. The sensitivity of either positive plasma or positive stool CMV-PCR was 81.5%, which is significantly higher than that of plasma CMV-PCR alone ( P = 0.045). However, positive results from both tests yielded a specificity of 95.8%, which is significantly higher than that of stool CMV-PCR alone ( P = 0.045). There was a good and significant correlation between stool CMV-PCR and plasma CMV-PCR ( r = 0.71, P < 0.01), and both tests significantly correlated with the cytomegalic cell count ( r = 0.62, P < 0.01 for stool and r = 0.64, P < 0.01 for plasma). There were no positive stool or plasma CMV-PCR assays among volunteers. DISCUSSION: The results of this study strongly suggest that the combination of stool CMV-PCR and plasma CMV-PCR can be used to confidently rule in (both positive) or rule out (both negative) a diagnosis of CMV colitis.

Diffuse gallbladder wall thickening in autoimmune hepatitis: an unusual presentation.

A 63-year-old woman presented with jaundice and epigastric pain for 2 weeks. Physical examination revealed marked jaundice, and palpable gallbladder with right upper quadrant tenderness. Liver function test was remarkable for hepatocellular injury pattern. Antinuclear antibody and anti-smooth muscle antibody were positive with high titre and serum IgG was elevated more than upper normal range. Ultrasound and CT scan demonstrated mildly diffuse periportal oedema of liver parenchyma and markedly diffuse gallbladder wall thickening up to 2 cm. Liver histology showed focal interface hepatitis with prominent plasma cell infiltration and cluster formation, moderate lobular spotty necrosis and emperipolesis consistent with autoimmune hepatitis. The patient was treated with steroid and azathioprine. She had complete resolution of symptoms and normal biochemical laboratory results. Diffuse gallbladder thickening was seen in acute hepatitis from definite autoimmune hepatitis.

Cartilage oligomeric matrix protein as a marker of progressive liver fibrosis in biliary atresia.

This study aimed to determine whether mRNA and protein levels of cartilage oligomeric matrix protein (COMP), a glycoprotein responsible for modulating homeostasis of extracellular matrix, in the systemic and local liver environments were associated with clinical parameters of biliary atresia (BA) patients and might serve as a biomarker for BA severity. COMP protein levels in the circulation of 96 BA patients and 56 healthy controls and its mRNA and protein expressions in the liver of 20 BA patients and 5 non-BA patients were evaluated using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry, respectively. In the circulation of BA patients, COMP levels were significantly higher than those in healthy controls. Compared with early-stage BA patients, those with advanced-stage including jaundice, fibrosis, and hepatic dysfunction had significantly increased circulating COMP levels. Raised circulating COMP levels were found to be independently correlated with degree of liver fibrosis. Survival analysis showed that elevated circulating COMP levels were significantly associated with decreased survival of BA patients. Receiver-operating characteristic curve analysis unveiled a diagnostic value of circulating COMP as a non-invasive biomarker of BA (AUC = 0.99), with a sensitivity of 100.0% and a specificity of 98.2%. In the liver, both COMP mRNA and protein expressions of BA patients with fibrosis were significantly greater than those of BA patients without fibrosis and non-BA patients. Collectively, increased circulating COMP might reflect unfavorable outcome of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.

Duodenal mature teratoma causing partial intestinal obstruction: A first case report in an adult.

BACKGROUND: A teratoma is a germ cell tumor that is composed of tissue derived from two or three germ layers. Duodenal teratomas are extremely rare and have been exclusively reported in neonates and children. This is the third case of a teratoma primarily arising in the duodenum and the first case that occurred in an adult. CASE SUMMARY: A 31-year-old male presented with clinical partial gut obstruction (epigastric pain, nausea, and vomiting). The physical examination showed a palpable ill-defined mass on the left side of the abdomen. The computed tomography scan revealed a multiseptated cystic tumor at the retroperitoneal area. First, he underwent gastrojejunostomy to relieve the symptoms and was referred to a tertiary-care hospital. The second operation revealed a 10-cm solid-cystic mass originating from the third part of the duodenum and adhering to the abdominal aorta and pancreas. Segmental duodenectomy was performed. The pathological diagnosis was a mature cystic teratoma. The patient was asymptomatic at 5 mo after the operation. CONCLUSION: Duodenal teratomas are extremely rare but should be included in the differential diagnosis in patients who present with intestinal obstruction. Radiological imaging is helpful to reach the preoperative diagnosis. Multidisciplinary team planning is essential to avoid injury to the adjacent organ in duodenal operation.

Hepatic glypican-3 and alpha-smooth muscle actin overexpressions reflect severity of liver fibrosis and predict outcome after successful portoenterostomy in biliary atresia.

BACKGROUND: Glypican-3 plays a vital role in regulating embryonic morphogenesis of the liver. This study aimed to investigate associations of hepatic expressions of glypican-3 and alpha-smooth muscle actin with clinical parameters in biliary atresia. METHODS: Liver specimens were obtained from 20 biliary atresia infants and 7 non-biliary atresia controls. Relative mRNA expressions of glypican-3, alpha-smooth muscle actin, and signaling molecules of Wnt/ß-catenin were measured using real-time polymerase chain reaction. Protein expressions of glypican-3 and alpha-smooth muscle actin were examined using immunohistochemistry. Masson's trichrome staining was conducted to evaluate the stage of liver fibrosis. RESULTS: Up-regulation of glypican-3 mRNA expression was observed in biliary atresia livers, and its expression was positively associated with alpha-smooth muscle actin, ß-catenin, c-Myc, and cyclin D-1. Immunostaining scores of glypican-3 and alpha-smooth muscle actin were significantly increased in biliary atresia livers. Biliary atresia patients with poor outcomes had significantly greater glypican-3 expression than those with good outcomes, consistent with hepatic alpha-smooth muscle actin expression analysis. Hepatic glypican-3 expression was associated with age, albumin, aspartate transaminase, and alkaline phosphatase in biliary atresia patients, while hepatic alpha-smooth muscle actin expression was correlated with alkaline phosphatase in the patients. Moreover, glypican-3 and alpha-smooth muscle actin expressions were positively associated with fibrosis stage in biliary atresia livers. There was a positive relationship between glypican-3 and alpha-smooth muscle actin expression in biliary atresia livers. Combined high expressions of glypican-3 and alpha-smooth muscle actin were associated with poor survival. CONCLUSION: Hepatic overexpressions of glypican-3 and alpha-smooth muscle actin were associated with hepatic dysfunction and the degree of liver fibrosis in biliary atresia.

Targeting GLP-1 receptor trafficking to improve agonist efficacy.

Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-coupled receptors, the GLP-1R undergoes agonist-mediated endocytosis, but the functional and therapeutic consequences of modulating GLP-1R endocytic trafficking have not been clearly defined. Here, we investigate a series of biased GLP-1R agonists with variable propensities for GLP-1R internalization and recycling. Compared to a panel of FDA-approved GLP-1 mimetics, compounds that retain GLP-1R at the plasma membrane produce greater long-term insulin release, which is dependent on a reduction in ß-arrestin recruitment and faster agonist dissociation rates. Such molecules elicit glycemic benefits in mice without concomitant increases in signs of nausea, a common side effect of GLP-1 therapies. Our study identifies a set of agents with specific GLP-1R trafficking profiles and the potential for greater efficacy and tolerability as T2D treatments.

Short article: Stool cytomegalovirus polymerase chain reaction for the diagnosis of cytomegalovirus-related gastrointestinal disease.

OBJECTIVES: The diagnosis of cytomegalovirus-related gastrointestinal disease (CMV-GI disease) still requires histopathology, but biopsy is considered invasive. Stool CMV PCR has been reported in adults as an alternative method to diagnose this condition; hence, the results between studies are discrepant. Moreover, no pediatric studies on stool CMV real-time PCR in CMV-GI disease have been carried out. Here, we evaluate the value of stool CMV real-time PCR in detecting CMV-GI disease among immunocompromised children. METHODS: We enrolled immunocompromised patients aged younger than 20 years who presented with gastrointestinal symptoms at a teaching hospital during January 2015-March 2016. Stool samples were analyzed for CMV real-time PCR. All patients underwent esophagogastroduodenoscopy and colonoscopy with mucosal biopsy. RESULTS: We performed stool CMV real-time PCR in 31 patients, but two could not undergo endoscopy. Therefore, 29 patients were analyzed. Two additional stool samples showed inhibitors that interfere with the PCR testing and were precluded from the final analysis. Among 27 patients, we found CMV-GI disease in seven (26%) patients. The sensitivity, specificity, and accuracy of stool CMV real-time PCR were 71, 85, and 82%, respectively. We also found that all patients with CMV-GI disease had positive plasma CMV real-time PCR (>150 copies/ml). A significant association between stool and plasma CMV real-time PCR was also noted (P<0.001). CONCLUSION: Stool CMV real-time PCR may be used as a noninvasive tool in the diagnosis of CMV-GI disease. Plasma CMV real-time PCR shows a significant correlation with stool CMV real-time PCR and also represents high diagnostic values.

Henoch-Schönlein purpura from vasculitis to intestinal perforation: A case report and literature review.

Henoch-Schönlein purpura (HSP) is generally a self-limited vasculitis disease and has a good prognosis. We report a 4-year-old Thai boy who presented with palpable purpura, abdominal colicky pain, seizure, and eventually developed intestinal ischemia and perforation despite adequate treatment, including corticosteroid and intravenous immunoglobulin therapy. Imaging modalities, including ultrasonography and contrast-enhanced computed tomography, could not detect intestinal ischemia prior to perforation. In this patient, we also postulated that vasculitis-induced mucosal ischemia was a cause of the ulcer, leading to intestinal perforation, and high-dose corticosteroid could have been a contributing factor since the histopathology revealed depletion of lymphoid follicles. Intestinal perforation in HSP is rare, but life-threatening. Close monitoring and thorough clinical evaluation are essential to detect bowel ischemia before perforation, particularly in HSP patients who have hematochezia, persistent localized abdominal tenderness and guarding. In highly suspicious cases, exploratory laparotomy may be needed for the definite diagnosis and prevention of further complications.

Abnormal layering of muscularis propria as a cause of chronic intestinal pseudo-obstruction: A case report and literature review.

Visceral myopathy is one of the causes of chronic intestinal pseudo-obstruction. Most cases pathologically reveal degenerative changes of myocytes or muscularis propia atrophy and fibrosis. Abnormal layering of muscularis propria is extremely rare. We report a case of a 9-mo-old Thai male baby who presented with chronic intestinal pseudo-obstruction. Histologic findings showed abnormal layering of small intestinal muscularis propria with an additional oblique layer and aberrant muscularization in serosa. The patient also had a short small bowel without malrotation, brachydactyly, and absence of the 2(nd) to 4(th) middle phalanges of both hands. The patient was treated with cisapride and combined parenteral and enteral nutritional support. He had gradual clinical improvement and gained body weight. Subsequently, the parenteral nutrition was discontinued. The previously reported cases are reviewed and discussed.

TOP2A amplification and overexpression in hepatocellular carcinoma tissues.

Hepatocellular carcinoma (HCC) is the leading cause of cancer death in men worldwide owing to limited insights into pathogenesis and unsatisfactory efficacy of current therapies. HER2 and TOP2A genes are coamplified in breast and some other cancers. In this study, we investigated gene aberrations of HER2 and TOP2A and protein expressions of HER2, TOP2A, Ki-67, and p53 in tumor and matched nontumor tissues, as well as their associations with clinicopathological features. Gene aberrations were evaluated by FISH and protein expressions by IHC. Neither HER2 overexpression nor HER2 gene amplification was observed in both tumor tissues and matched nontumor tissues. By contrast, TOP2A overexpression was detected in 72.5% of tumor tissues but not detected in matched nontumor tissues. However, TOP2A gene amplification was not observed in both tumor and matched nontumor tissues. TOP2A overexpression was significantly associated with HCC tumor tissues (P < 0.001), hepatitis B surface antigen (HBsAg) in the serum (P = 0.004), and Ki-67 (P = 0.038) but not with age, tumor size, alpha-fetoprotein, TP53, and copy number of TOP2A gene and chromosome 17 centromere. In conclusion, TOP2A overexpression in HCC was not secondary to gene amplification. In addition, neither HER2 amplification nor overexpression could be used as prognostic and predictive marker in HCC.