A novel saliva-based miRNA profile to diagnose and predict oral cancer

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

Small intestine angioleiomyoma as a rare cause of perforation:A case report

BACKGROUND Angioleiomyoma is a rare and benign stromal tumor typically found in subcutaneous tissue.It rarely occurs in the gastrointestinal tract.Among the reported cases,the most common complication was gastrointestinal bleeding.Perforation has only been reported as a complication in the last few decades.CASE SUMMARY This case report detailed the discovery of intestinal angioleiomyoma in a 47-yearold male presenting with abdominal pain that had persisted for 3 d.After suspecting hollow organ perforation,surgical intervention involving intestinal resection and anastomosis was performed.CONCLUSION The report underscores the significance of early surgical intervention in effectively treating angioleiomyoma while emphasizing the pivotal role of timely and appropriate measures for favorable outcomes.

Predictors of survival in autoimmune liver disease overlap syndromes

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort study.Liver-related death or transplantation(liver-related mortality)was determined using a population-based data linkage system.Prognostic scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and AIH-PSC.LOS was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.CONCLUSION Survival in the rare,AILDOS is unclear.The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients.Further trials investigating predictors of survival in AILDOS are required.

Assessment and Visualization of Ki67 Heterogeneity in Breast Cancers through Digital Image Analysis

The Ki67 index (KI) is a standard clinical marker for tumor proliferation;however, its application is hindered by intratumoral heterogeneity. In this study, we used digital image analysis to comprehensively analyze Ki67 heterogeneity and distribution patterns in breast carcinoma. Using Smart Pathology software, we digitized and analyzed 42 excised breast carcinoma Ki67 slides. Boxplots, histograms, and heat maps were generated to illustrate the KI distribution. We found that 30% of cases (13/42) exhibited discrepancies between global and hotspot KI when using a 14% KI threshold for classification. Patients with higher global or hotspot KI values displayed greater heterogenicity. Ki67 distribution patterns were categorized as randomly distributed (52%, 22/42), peripheral (43%, 18/42), and centered (5%, 2/42). Our sampling simulator indicated analyzing more than 10 high-power fields was typically required to accurately estimate global KI, with sampling size being correlated with heterogeneity. In conclusion, using digital image analysis in whole-slide images allows for comprehensive Ki67 profile assessment, shedding light on heterogeneity and distribution patterns. This spatial information can facilitate KI surveys of breast cancer and other malignancies.

Comparative Analysis of Ki-67 Protein as a Proliferative Expression Index in Cutaneous Basal and Squamous Cell Carcinoma in Federal Medical Centre Umuahia, Nigeria

Background: Evaluating the tumor proliferative index helps predict clinical behavior and provides prognostic insights for cutaneous basal cell carcinoma (cBCC) and squamous cell carcinoma (cSCC). Objective: This study aimed to identify differences in the proliferative indices among variants of cBCC and cSCC diagnosed at a tertiary healthcare center. Method: Skin biopsies histologically diagnosed as cBCC and cSCC between 2012 and 2018 at the Federal Medical Centre (FMC) Umuahia, Abia State, Nigeria, were analyzed. Archival formalin-fixed, paraffin-embedded (FFPE) tissue blocks were retrieved along with clinical data, and were prepared on charged microscope slides and the immunohistochemical staining was carried out. The primary antibody used in this study was clone BioCare CRM325C (RM) and adenotonsillar tissue blocks/slides served as positive controls. Ki-67 immunohistochemistry was performed on fresh 4µm sections of the tumor specimens. Results: The application of Ki-67 immunoperoxidase on both BCC and SCC cohort, yielded an intense observable brownish nuclear stain in areas of dense proliferating tumour cells on both cutaneous tumours. The average Ki-67 index for all cSCC cases was 24.7%, with a range of 2.3% - 80%, while the mean for cBCC was 15.8%, ranging from 1.2% - 45.6%. Variants with high proliferative indices were observed in 11.9% of cBCC cases and 29.1% of cSCC cases. Among the low proliferative index category, cSCC accounted for 5.4%, while cBCC represented 14.3%. For mild proliferative indices, cSCC cases made up 7.3% and cBCC, 11.9%. The majority of cases showed moderate proliferative indices, with 61.9% for cBCC and 58.2% for cSCC. Overall, there was a significant difference in proliferative indices between cSCC, cBCC, and their variants. Conclusion: The study found a significantly higher rate of cell proliferation, measured by Ki-67 immunostaining, in cSCC and its variants compared to cBCC. However, certain variants of cBCC also exhibited high Ki-67 expression, indicating they can be as aggressive as some cSCC variants.

Patients with early recurrence of hepatocellular carcinoma have poor prognosis

BACKGROUND： Early recurrence （ER） after hepatic resection （HR） is a poor prognostic factor for patients with hepatocellular carcinoma （HCC）. This study aimed to identify the clinico- pathological features, outcomes, and risk factors for ER after HR for small HCC in order to clarify the reasons why ER is a worse recurrence pattern. METHODS： We retrospectively examined 130 patients who underwent HR for small HCC （___30 mm）. Recurrence was clas- sifted into ER （〈2 years） and late recurrence （LR） （_〉2 years）. The clinicopathological features, outcomes, and risk factors for ER were analyzed by multivariate analysis. RESULTS： ER was observed in 39 patients （30.0%）. The sur- vival rate of the ER group was significantly lower than that of the LR group （P〈0.005）, and ER was an independent prognos- tic factor for poor survival （P=0.0001）. The ER group had a significantly higher frequency （P=0.0039） and shorter interval （P=0.027） of development to carcinoma beyond the Milan criteria （DBMC） compared with the LR group, and ER was an independent risk factor for DBMC （P〈0.0001）. Multi-nodularity, non-simple nodular type, and microvascular invasion were independent predictors for ER （P=0.012, 0.010, and 0.019, respectively）.CONCLUSIONS： ER was a highly malignant recurrence pattern associated with DBMC and subsequent poor survival after HR for small HCC. Multi-nodularity, non-simple nodular type, and microvascular invasion predict ER, and taking these factors into consideration may be useful for the decision of the treatment strategy for small HCC after HR.

Cyclooxygenase-2 and epithelial growth factor receptor up-regulation during progression of Barrett's esophagus to adenocarcinoma

AIM： To investigate the expression of cyclooxygenase-2 （COX-2） and epithelial growth factor receptor （EGFR） throughout the progression of Barrett＇s esophagus （BE）. METHODS： COX-2 and EGFR protein expressions were detected by using immunohistochemical method. A detailed cytomorphological changes were determined. Areas of COX-2 and EGFR expression were quantified by using computer Imaging System. RESULTS： The expressions of both COX-2 and EGFR increased along with the progression from BE to esophagus adenocarcinoma （EAC）. A positive correlation was found between COX-2 expression and EGFR expression. CONCLUSION： COX-2 and EGFR may be cooperative in the stepwise progression from BE to EAC, thereby leading to carcinogenesis.

Profile of hepatocyte apoptosis and bile lakes before and after bile duct decompression in severe obstructive jaundice patients

BACKGROUND:Excessive hepatocyte apoptosis and bile lakes in severe obstructive jaundice might impair liver functions.Although decompression of the bile duct has been reported to improve liver functions in animal studies,the mechanism of obstruction differs from that in humans.This study aimed to determine the profiles of hepatocyte apoptosis and bile lakes following bile duct decompression in patients with severe obstructive jaundice in the clinical setting.METHODS:We conducted a 'before and after study' on severe obstructive jaundice patients as a model of inhibition of the excessive process by bile duct decompression.Specimens of liver biopsies were taken before and after decompression of the bile duct and then stained by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling(TUNEL) to identify hepatocyte apoptosis and by hematoxilin-eosin(HE) to identify bile lakes.All measurements were independently done by 2 observers.RESULTS:Twenty-one severe obstructive jaundice patients were included.In all patients,excessive hepatocyte apoptosis and bile lakes were apparent.After decompression,the hepatocyte apoptosis index decreased from 53.1(SD 105) to 11.7(SD 13.6)(P<0.05),and the bile lakes from 23.6(SD 14.8) to 10.9(SD 6.9)(P<0.05).CONCLUSION:Bile duct decompression improves hepatocyte apoptosis and bile lakes in cases of severe obstructive jaundice,similar to the findings in animal studies.

Emergent single-balloon enteroscopy for overt bleeding of small intestinal vascular malformation

A 28-year-old man presented with anemia symptoms and intermittent tarry stool passage for three days. No stigmata of hemorrhage were identified using esophagogastroduodenoscopy, ileocolonoscopy, and contrast-enhanced computed tomography. He then developed massive tarry stool passage with profound hypovolemic shock and hypoxic respiratory failure. Emergent angiography revealed active bleeder, probably from the jejunal branches of the superior mesenteric artery, but embolization was not performed due to possible subsequent extensive bowel ischemia. His airway was secured via endotracheal intubation with ventilator support, and emergent antegrade singleballoon enteroscopy was performed at 8 h after clinical overt bleeding occurrence; the procedure revealed a 2-cm pulsating subepithelial tumor with a protrudingblood plug at the distal jejunum. Laparoscopic segmental resection of the jejunum with end-to-end anastomosis was performed after emergent endoscopic tattooing localization. Pathological examination revealed a vascular malformation in the submucosa with an organizing thrombus. He was uneventfully discharged 5 d later. This case report highlights the benefit of early deep enteroscopy for the treatment of small intestinal bleeding.

Myoepithelial carcinoma of the stomach: A diagnostic pitfall

Myoepithelioma/myoepithelial carcinomas are not commonly found in soft tissues and are especially rare at visceral sites.This report describes a case of a rare low-grade myoepithelial carcinoma of the stomach.A61-year-old female patient presented with postprandial abdominal discomfort.Endoscopy revealed a 1.1 cm submucosal lesion.Local excision was performed after malignancy was confirmed by biopsy.The resection margin is free of tumor and she received no adjuvant therapy.The tumor was characterized by multinodular growth with biphasic epithelioid and spindle components.Infiltrative margin and nuclear pleomorphism are seen.Tumor cells were positive for both epithelial and myoepithelial markers.Evidence of epithelial differentiation was confirmed by electron microscopy.No EWSR1 rearrangement was detected.The final diagnosis was low-grade myoepithelial gastric carcinoma.The patient is currently well, and no evidence of recurrence or metastasis was found after ten-month of follow-up.Myoepithelial carcinoma should be considered in the differential diagnosis of a biphasic gastric tumor.

Histopathological profile of gastritis in adult patients seen at a referral hospital in Kenya

AIM： To conduct a detailed histological study of gastritis in adult patients attending an endoscopy clinic at a Kenyan teaching and referral hospital.METHODS： Biopsy specimens from consecutive patients were examined and graded according to the Updated Sydney System for H pylori infection, chronic inflammation, neutrophil activity, glandular atrophy and intestinal metaplasia. Also documented were gastric tissue eosinophil counts and presence of lymphoid follicles.RESULTS： The rate of the graded variables, in the antrum and corpus respectively, were as follows： H pylori infection （91%, 86%）, chronic inflammation （98%, 93%）, neutrophil activity （91%, 86%）, glandular atrophy （57%, 15%） and intestinal metaplasia （11%, 2%）. Lymphoid follicles were noted in 11% of cases. Duodenal and gastric ulcers were documented in 32% and 2% respectively. The mean eosinophil count was 5.9 ±0.74 eosinophils/ HPF and 9.58 ± 0.93 eosinophils/HPF in the corpus and antrum respectively. Significant association was found between the degree of H pylori colonisation with chronic inflammation, neutrophil activity and antral glandular atrophy. Biopsies from the antrum and corpus showed significant histopathological discordance for all the graded variables. H pylori negative cases were associated with recent antibiotic use.CONCLUSION： The study the chief cause of gastritis reaffirms that H pylori is in this environment. The majority of patients show a moderate to high degree of inflammation but a low degree of glandular atrophy and intestinal metaplasia. The study shows that interrelationships between the histological variables in this African population are similar to those found in other populations worldwide including non-African populations.

MicroRNA profile in neosquamous esophageal mucosa following ablation of Barrett's esophagus

To investigate the microRNA expression profile in esophageal neosquamous epithelium from patients who had undergone ablation of Barrett’s esophagus. METHODSHigh throughput screening using TaqMan® Array Human MicroRNA quantitative PCR was used to determine expression levels of 754 microRNAs in distal esophageal mucosa (1 cm above the gastro-esophageal junction) from 16 patients who had undergone ablation of non-dysplastic Barrett’s esophagus using argon plasma coagulation vs pretreatment mucosa, post-treatment proximal normal non-treated esophageal mucosa, and esophageal mucosal biopsies from 10 controls without Barrett’s esophagus. Biopsies of squamous mucosa were also taken from 5 cm above the pre-ablation squamo-columnar junction. Predicted mRNA target pathway analysis was used to investigate the functional involvement of differentially expressed microRNAs. RESULTSForty-four microRNAs were differentially expressed between control squamous mucosa vs post-ablation neosquamous mucosa. Nineteen microRNAs were differentially expressed between post-ablation neosquamous and post-ablation squamous mucosa obtained from the more proximal non-treated esophageal segment. Twelve microRNAs were differentially expressed in both neosquamous vs matched proximal squamous mucosa and neosquamous vs squamous mucosa from healthy patients. Nine microRNAs (miR-424-5p, miR-127-3p, miR-98-5p, miR-187-3p, miR-495-3p, miR-34c-5p, miR-223-5p, miR-539-5p, miR-376a-3p, miR-409-3p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These microRNAs were also more highly expressed in Barrett’s esophagus mucosa than matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these microRNAs may be involved in the regulation of cell survival signalling pathways. Three microRNAs (miR-187-3p, miR-135b-5p and miR-31-5p) were expressed at higher levels in post-ablation neosquamous mucosa than in matched proximal squamous and healthy squamous mucosa. These miRNAs were expressed at similar levels in pre-ablation Barrett’s esophagus mucosa, matched proximal squamous and squamous mucosa from controls. Target prediction and pathway analysis suggests that these microRNAs may be involved in regulating the expression of proteins that contribute to barrier function. CONCLUSIONNeosquamous mucosa arising after ablation of Barrett’s esophagus expresses microRNAs that may contribute to decreased barrier function and microRNAs that may be involved in the regulation of survival signaling pathways.

Gut-associated lymphoid tissue or so-called “dome” carcinoma of the colon: Review

AIM To present a comprehensive review of the etiology, clinical features, macroscopic and pathological findings, and clinical significance of Gut-associated lymphoid tissue or "dome" carcinoma of the colon.METHODS The English language medical literature on gut-or gastrointestinal-associated lymphoid tissue(GALT) or "dome" carcinoma of the colon was searched and appraised.RESULTS GALT/dome-type carcinomas of the colon are thought to arise from the M-cells of the lymphoglandular complex of the intestine. They are typically asymptomatic and have a characteristic endoscopic plaque-or "dome"-like appearance. Although the histology of GALT/dome-type carcinomas displays some variability, they are characterized by submucosal localization, a prominent lymphoid infiltrate with germinal center formation, tumor-infiltrating lymphocytes, absence of desmoplasia, and dilated glands lined by columnar epithelial cells with bland nuclear features and cytoplasmic eosinophilia. None of the patients reported in the literature with follow-up have developed metastatic disease or local recurrence.CONCLUSION Increased awareness amongst histopathologists of this variant of colorectal adenocarcinoma is likely to lead to the recognition of more cases.

A rare case of isolated castrate resistant bilateral testicular metastases in advanced prostate cancer

Testicular metastasis is rare with the prostate being the most common site of primary cancer.We report a case of a 72-year-old man with castration-resistant prostate cancer(CRPC)and known metastases to bone and lymph nodes,who developed bilateral painful swollen testes 3 years after the initial diagnosis of prostate cancer.He had first presented with lower urinary tract symptoms(LUTS)with suspicious findings on digital rectal examination of the prostate,and an elevated serum prostate specific antigen(PSA)level of 129 ng/mL.Transrectal prostate biopsy revealed Gleason 4þ5 adenocarcinoma.Radiological staging showed locally advanced prostate cancer with extensive metastases to bone and pelvic and retroperitoneal lymph nodes.He was given hormonal therapy for over 2 years until progression to CRPC.Six months later he developed painful bilateral testicular swellings,and serum markers for testicular germ cell cancer were normal.Bilateral orchiectomy was performed,showing metastatic prostate cancer(Gleason 4þ5)on histology.One month postoperatively his PSA level dropped to 0.1 ng/mL from a presurgery level of 6.24 ng/mL.

Amyloid-beta-dependent phosphorylation of collapsin response mediator protein-2 dissociates kinesin in Alzheimer＇s disease

Alzheimer’s disease（AD）is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles.Prior to the development of these characteristic pathological hallmarks of AD,anterograde axonal transport is impaired.However,the key proteins that initiate these intracellular impairments remain elusive.The collapsin response mediator protein-2（CRMP-2）plays an integral role in kinesin-1-dependent axonal transport and there is evidence that phosphorylation of CRMP-2releases kinesin-1.Here,we tested the hypothesis that amyloid-beta（Aβ）-dependent phosphorylation of CRMP-2 disrupts its association with the kinesin-1（an anterograde axonal motor transport protein）in AD.We found that brain sections and lysates from AD patients demonstrated elevated phosphorylation of CRMP-2 at the T555 site.Additionally,in the transgenic Tg2576 mouse model of familial AD（FAD）that exhibits Aβaccumulation in the brain with age,we found substantial co-localization of p T555CRMP-2and dystrophic neurites.In SH-SY5Y differentiated neuronal cultures,Aβ-dependent phosphorylation of CRMP-2 at the T555 site was also elevated and this reduced the CRMP-2 association with kinesin-1.The overexpression of an unphosphorylatable form of CRMP-2 in neurons promoted the re-establishment of CRMP-2-kinesin association and axon elongation.These data suggest that Aβ-dependent phosphorylation of CRMP-2 at the T555 site may directly impair anterograde axonal transport protein function,leading to neuronal defects.

Design and Molecular Docking Study of Antimycin A₃Analogues as Inhibitors of Anti-Apoptotic Bcl-2 of Breast Cancer

In this paper, we report the design and moleculardocking study of analogues of antimycin A3 as inhibitors of anti-apoptotic Bcl-2 of breast cancer. Twenty designed compounds and the original antimycin A3 were docked based on their interaction with breast tumor receptor binding target Bcl-2. The docking resulted in the five top-ranked compounds, namely, compounds 11, 14, 15, 16, and 20, which have a lower G binding energy, better affinity and stronger hydrogen bonding interactions to the active site of Bcl-2 than antimycin A3. Among those five top-ranked compounds, analogue compounds 11 and 14, which have an 18-membered tetralactone core and 18-membered tetraol core, respectively, exhibited the strongest hydrogen bond interaction, formed high stability conformation, and demonstrated the greatest inhibitory activity on the catalytic site of Bcl-2.

The Role of Dutasteride in Acute Prostatic Haematuria

Background: Dutasteride has been found to reduce chronic prostatic bleeding and when taken 2 - 6 weeks preoperatively reduces bleeding during transurethral prostate resection. The aim of this study is to determine if the drug will be effective in the control of acute gross prostatic haematuria. Patients and Method: 87 Consecutive patients with gross haematuria were enrolled. Clotting Profile, Cystoscopy and Intravenous Urography were done to exclude haematuria from medical, renal and bladder causes. Patients suspected to have prostatic haematuria were further evaluated using serum Prostate specific antigen (PSA) and Prostate scan. Those with elevated PSA ≥ 10 ng/ml and abnormal digital rectal examination (DRE) finding had prostate biopsy. The patients were randomly divided into 2 treatment groups. The control group had Normal saline irrigation and broad spectrum antibiotics while the second group received 0.5 mg oral dutasteride in addition. The time taken and volume of irrigation fluid used before haematuria stopped were noted. Statistical analysis was done using SPSS version 20.0. Result: 75 patients had haematuria of prostatic origin. 49 (65.3%) of these had benign prostatic hyperplasia (BPH) and 26 (34.7%) had cancer of prostate. 25(51%) of the 49 patients with BPH had Normal saline irrigation and antibiotics while 24 (49%) had oral dutasteride in addition. 14 (53.8%) of the prostate cancer patients had Normal saline irrigation and antibiotics while 12 (46.2%) had dutasteride in addition. Haematuria resolved in significantly shorter length of time using lesser volume of irrigation fluid in those treated with dutasteride than in those on control arm. Conclusion: Addition of 0.5 mg oral dutasteride daily leads to early resolution of acute prostatic haematuria.

Involvement of Krüppel-like factor 6 (KLF6) mutation in the development of nonpolypoid colorectal carcinoma

AIM： To examine Kruppel-like factor 6 （KLF6） mutations in nonpolypoid-type tumors and alterations of K-ras, p53, and B-raf in relation between mutation and morphologic type, particularly nonpolypoid-type colorectal carcinomas. METHODS： Fifty-five early nonpolypoid colorectal carcinomas were analyzed. Loss of heterozygosity （LOH） of KLF6 and p53 was determined by microsatellite assay. Mutations of KLF6, K-ras, and B-raf were examined by polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing. In LOH- positive and/or mutation-positive tumors, multiple （4-7） samples in each tumor were microdissected and examined for genetic alterations, p53 expression was evaluated by immunohistochemistry. RESULTS： LOH of KLF6 and p53 was found in 14 of 29 （48.3%） and 14 of 31 （45.2%） tumors, respectively. In tO of the 14 （71.4%） KLF6 LOH-positive tumors and 9 of the 14 （64.3%） p53 LOH-positive tumors, LOH was found in all of the microdissected samples. In 1 of the tO （10.0%） KLF6 LOH-positive tumors, a single missense mutation was identified. K-ras and B-raf mutations were found in 5 of 55 （9.1%） and 6 of 55 （10.9%） tumors, respectively. However, these mutations were detected only in subsets of microdissected tumor samples. CONCLUSION： These data suggest that KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not.

Improved Hepascore in hepatitis C predicts reversal in risk of adverse outcome

AIM To establish if serial Hepascore tests(referred to as delta Hepascore) in those with chronic hepatitis C(CHC) correlate with the increase and/or decrease in risk of liver related complications.METHODS Three hundred and forty-six CHC patients who had two Hepascore tests performed were studied. During 1944 patient years follow-up 28(8.1%) reached an endpoint. The Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis andsubsequent clinical outcomes in chronic liver disease.RESULTS Patients with a baseline Hepascore > 0.75 had a significantly increased rate of reaching a composite endpoint consisting of hepatocellular carcinoma, liver death, and/or decompensation(P < 0.001). In those with an initial Hepascore > 0.75, a subsequent improved Hepascore showed a significantly decreased risk for the composite endpoint(P = 0.004). There were no negative outcomes in those with a stable or improved delta Hepascore. The minimum time between tests that was found to give a statically significant result was in those greater than one year(P = 0.03).CONCLUSION In conclusion, Hepascore is an accurate predictor of liver related mortality and liver related morbidity in CHC patients. Of note, we have found that there is a decreased risk of mortality and morbidity in CHC patients when the patient has an improving delta Hepascore. Repeat Hepascore tests, when performed at a minimum one-year interval, may be of value in routine clinical practice to predict liver related clinical outcomes and to guide patient management.

Isolated IgG4-associated autoimmune hepatitis or the first manifestation of IgG4-related disease?

To the Editor:Immunoglobulin G4(IgG4)-associated autoimmune hepatitis(IgG4-AIH)is a novel and rare disease entity,characterized by sig-nificant infiltration of IgG4-expressing plasma cells in the liver.The classification of of IgG4-AIH as a subtype of AIH or an early manifestation of IgG4-related disease(IgG4-RD)remains controversial.Herein,we discuss an interesting clinical vignette of IgG4-AIH in a gentleman with no significant past medical history,who presented with undifferentiated symptoms and elevated aminotransferases.