Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management

Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.

Impact of the economic crisis and drug shortage on Lebanese cancer patients’care

BACKGROUND As a consequence of the economic crisis,the sociopolitical instability and the advent of the coronavirus disease-19 pandemic,nested challenges faced the Lebanese healthcare system.These have resulted in critical shortages of essential resources,including medications vital for oncologic patients.AIM To assess the ramifications of the ongoing economic crisis on oncology patient care focusing on our outpatient oncology department.METHODS A questionnaire was distributed during the month of February 2022 to oncology patients in Hôtel Dieu de France University Hospital in Beirut during their outpatient therapy.The primary objective was to assess the far-reaching impact of the economic crisis on patient care and the resulting psychological implications.RESULTS Among 182 interviewed patients,31.87%experienced treatment interruption mainly due to acute drug shortages.Despite 87.91%of the patients benefiting from third-party coverage,69.60%had to self-pay for their medications leading to 69.78%of patients perceiving that healthcare was more difficult to access after 2020.Psychologically,one-third of the patients exhibited symptoms of anxiety and/or depression,with 7 patients reporting suicidal ideations.Notably,37.93%of patients who interrupted cancer treatment reported a history of comorbidities,and 89.66%who altered their treatment cited financial difficulties.CONCLUSION Lebanese cancer patients face complex challenges spanning economic,healthcare,and psychological realms.Income inequalities exacerbated by the economic crisis hindered healthcare access.

Navigating the labyrinth of long non-coding RNAs in colorectal cancer:From chemoresistance to autophagy

Long non-coding RNAs(lncRNAs),with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity,have been found to impact colorectal cancer(CRC)through various biological processes.LncRNA expression can regulate autophagy,which plays dual roles in the initiation and progression of cancers,including CRC.Abnormal expression of lncRNAs is associated with the emergence of chemoresistance.Moreover,it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance.Two recent studies titled“Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506”and“Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription”revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC,respectively.In this editorial,we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.

Prevalence of malignant neoplasms in celiac disease patients-a nationwide United States population-based study

BACKGROUND Celiac disease(CeD)is an autoimmune disorder triggered by the immune response to gluten in genetically predisposed individuals.Recent research has unveiled a heightened risk of developing specific malignant neoplasms(MN)and various malignancies,including gastrointestinal,lymphomas,skin,and others,in individuals with CeD.AIM To investigate the prevalence of MN in hospitalized CeD patients in the United States.METHODS Using data from the National Inpatient Sample spanning two decades,from January 2000 to December 2019,we identified 529842 CeD patients,of which 78128(14.75%)had MN.Propensity score matching,based on age,sex,race,and calendar year,was employed to compare CeD patients with the general non-CeD population at a 1:1 ratio.RESULTS Positive associations were observed for several malignancies,including small intestine,lymphoma,nonmelanoma skin,liver,melanoma skin,pancreas myelodysplastic syndrome,biliary,stomach,and other neuroendocrine tumors(excluding small and large intestine malignant carcinoid),leukemia,uterus,and testis.Conversely,CeD patients exhibited a reduced risk of respiratory and secondary malignancies.Moreover,certain malignancies showed null associations with CeD,including head and neck,nervous system,esophagus,colorectal,anus,breast,malignant carcinoids,bone and connective tissues,myeloma,cervix,and ovary cancers.CONCLUSION Our study is unique in highlighting the detailed results of positive,negative,or null associations between different hematologic and solid malignancies and CeD.Furthermore,it offers insights into evolving trends in CeD hospital outcomes,shedding light on advancements in its management over the past two decades.These findings contribute valuable information to the understanding of CeD’s impact on health and healthcare utilization.

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CONCLUSION LncRNA HAND2-AS1 promotes TIMP2 expression by targeting miR-873-5p to inhibit HepG2 cell growth and delay HCC progression.

The challenge of molecular selection in liver-limited metastatic colorectal cancer for surgical resection: a systematic review and meta-analysis in the context of current and future approaches

Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this procedure.This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC(i.e.,RAS,BRAF,SMAD4,PIK3CA)as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection.Methods:A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM,stratified according to RAS,BRAF,PIK3CA,and SMAD4 mutational status.Hazard ratios(HRs)from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined.The search was conducted in numerous databases,including MEDLINE(PubMed),Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL)(EBSCO host),and WHO Global Index Medicus,through March 18th,2022.Meta-analyses,editorials,letters to the editor,case reports,studies on other primary cancers,studies with primary metastatic sites other than the liver,studies lacking specific oncological outcome variables or genetic data,non-English language studies,and studies omitting residual disease data from liver metastasectomy were excluded.The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented.Results:RAS mutation status was negatively associated with overall survival(OS)(HR,1.68;95%CI,1.54–1.84)and recurrence free survival(RFS)(HR,1.46;95%CI,1.33–1.61).A negative association was also found for BRAF regarding OS(HR,2.64;95%CI,2.15–3.24)and RFS(HR,1.89;95%CI,1.32–2.73)and SMAD4 regarding OS(HR,1.93;95%CI,1.56–2.38)and RFS(HR,1.95;95%CI,1.31–2.91).For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted.Conclusion:RAS,BRAF,and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer.No conclusion can be drawn for PIK3CA due to the limited literature availability.These data support the integration of RAS,BRAF,and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis.Nevertheless,we have to consider several limitations,the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival(DFS)or RFS;the inclusion of patients with minimal residual disease and unconsidered potential confounding factors,such as variability in resectability definitions,chemotherapy use,and a potential interaction between biological markers and pre-and post-resection pharmacological treatments.

Retrospective study evaluating association of colorectal tumors and hepatitis C virus

BACKGROUND Chronic hepatitis C virus(HCV)has been associated with hepatic and extrahe-patic malignancies.Limited studies have shown an association between colorectal adenomas and HCV populations.AIM To study the prevalence of colorectal adenomas in patients with HCV compared to the general population and to evaluate if it is an independent risk factor for colorectal adenomas.METHODS Patients were divided into HCV and non-HCV based on their HCV RNA titers.Patients with alcoholic liver disease,hepatitis B infection,and inflammatory bowel disease were excluded.Continuous variables were analyzed using the Mann-Whitney U test,and categorical variables usingχ^(2) with P<0.05 were considered statistically significant.The significant covariates(independent variables)were matched in both groups by propensity score matching,followed by multivariate regression analysis.RESULTS Of the 415 patients screened,109 HCV patients and 97 non-HCV patients with colonoscopy results were included in the study.HCV patients were older,had a smoking history,had less frequent aspirin use,and had a lower body mass index(BMI)(P<0.05).The HCV cohort had a significantly increased number of patients with adenomas(adenoma detection rate of 53.2%vs 34%.P=0.006).We performed a propensity-matched multivariate analysis where HCV infection was significantly associated with colorectal adenoma(OR:2.070,P=0.019).CONCLUSION Our study shows a significantly higher rate of adenomas in HCV patients compared to the general population.Prospective studies would help determine if the increase in adenoma detection lowers the risk for colorectal cancer.

Etiology of Pancytopenia in Tabriz Shahid Ghazi Hospital:A Cross-sectional Study in Iran

Objective:Pancytopenia is characterized by a reduction in all three types of blood cells:erythrocytes,leukocytes,and platelets.Pancytopenia is caused by a wide range of diseases,leading to diagnostic conundrums.These causes can range from drug reactions to life-threatening diseases such as aplastic anemia and leukemia.This study aims to investigate the causes of pancytopenia,specifically focusing on age and gender differences among patients.Methods:This cross-sectional study includes patients of all ages diagnosed with pancytopenia,as indicated by a CBC/H1 showing a WBC count less than 4,000/μL,platelet count less than 150,000/μL,and hemoglobin levels below 12 g/dL in women and less than 13 g/dL in men.The study only included patients with pancytopenia who underwent bone marrow examination and were not subjected to chemotherapy or radiation therapy.Results:A total of 133 patients with pancytopenia were included in the study.The average age was 47.35±17.62 years old,with 66%of the participants being male and 34%being female.Acute leukemia,specifically acute myeloid leukemia(AML)and acute lymphoid leukemia(ALL),was identified as the primary cause of pancytopenia,accounting for 31.5%of cases.Megaloblastic anemia was the second most common cause,accounting for 30%of cases,followed by aplastic anemia at 7.5%.Conclusion:Pancytopenia,a condition marked by the decrease in both erythrocytes and leukocytes as well as thrombocytes,can arise from a myriad of causes.The main findings of this study revealed that megaloblastic anemia,acute myeloid leukemia(AML),and acute lymphoid leukemia(ALL)were the most common causes.Significantly,a considerable proportion of cases of pancytopenia can be attributed to acute leukemia.Hence,expeditious and accurate diagnosis is imperative and has the potential to save lives in such cases.

Primary prevention and treatment of venous thromboembolic events in patients with gastrointestinal cancers- Review

Venous thromboembolism event(VTE) is a common and morbid complication in cancer patients. Patients with gastrointestinal cancers often suffer from symptomatic or incidental splanchnic vein thrombosis, impaired liver function and/or thrombocytopenia. These characteristics require a thorough risk/benefit evaluation for individual patients. Considering the risk factors for the development of VTE and bleeding events in addition to recent study results may be helpful for correct initiation of primary pharmacological prevention and treatment of cancer-associated thrombosis(CAT), preferably with low molecular weight heparins(LMWH). Whereas thromboprophylaxis is most often recommended in hospitalized surgical and non-surgical patients with malignancy, there is less agreement as to its duration. With regard to ambulatory cancer patients, the lack of robust data results in low grade recommendations against routine use of anticoagulant drugs. Anticoagulation with LMWH for the first months is the evidence-based treatment for acute CAT, but duration of secondary prevention and the drug of choice are unclear. Based on published guidelines and literature, this review will focus on prevention and treatment strategies of VTE in patients with gastrointestinal cancers.

ROLE OF B LYMPHOCYTE AND ITS SUBPOPULATIONS IN PATHOGENESIS OF IMMUNORELATED PANCYTOPENIA

Objective To measure the quantities and apoptosis-related protein levels of B lymphocyte in the patients with immunorelated pancytopenia （IRP） and explore the action of B lymphocyte in the pathogenic mechanism of IRP. Methods Quantifies of whole B lymphocytes and CD5^＋ B lymphocytes as well as the expressions of Fas and Bcl-2 in B lymphocytes in 35 patients with untreated IRP, 15 IRP patients in complete remission （CR）, and 10 normal controls were assayed by flow cytometry. The percentages of B lymphocyte and CD5^＋ B lymphocyte were significantly higher in untreated IRP patients than in CR IRP patients and normal controls （ P 〈 0. 05 ）, and there was no significant difference between the latter two groups （ P 〉 0. 05 ）. There was no significant difference of Fas expression in B lymphocyte among three groups （ P 〉 0. 05）. The expression of Bcl-2 in B lymphocyte was significantly higher in untreated patients than in CR patients or normal controls （ P 〈 0. 01 ）, and significantly higher in CR patients than in normal controls （ P 〈 0. 01 ）. The apoptosis. related index was significantly lower in untreated patients than in CR patients or normal controls （ P 〈 0. 05 ）, and signif. icantly lower in CR patients than in normal controls （ P 〈 0. 05 ）. The percentage of B lymphocyte was positively correlated with post-treated response time （ r = 0. 53, P 〈 0. 01 ）. Conclusion The production of auto-antibodies in IRP patients probably has some relationship with the abnormal quantifies of B lymphocyte and its subpopulations as well as with the inhibition of B lymphocyte apoptosis.

Long-term follow-up after complete ablation of Barrett's esophagus with argon plasma coagulation

AIM: To report the long-term outcome of patients after complete ablation of non-neoplastic Barrett's esophagus (BE) with respect to BE relapse and development of intraepithelial neoplasia or esophageal adenocarcinoma. METHODS: In 70 patients with historically proven non neoplastic BE, complete BE ablation was achieved by argon plasma coagulation (APC) and high-dose proton pump inhibitor therapy (120 mg omeprazole daily). Sixty-six patients (94.4%) underwent further surveillance endoscopy. At each surveillance endoscopy four-quadrant biopsies were taken from the neo-squamous epithelium at 2 cm intervals depending on the pre-treatment length of BE mucosa beginning at the neo-Z-line, and from any endoscopically suspicious lesion. RESULTS: The median follow-up of 66 patients was 51 mo (range 9-85 mo) giving a total of 280.5 patient years. A mean of 6 biopsies were taken during surveillance endoscopies. In 13 patients (19.7%) tongues or islands suspicious for BE were found during endoscopy. In 8 of these patients (12.1%) non-neoplastic BE relapse was confirmed histologically giving a histological relapse rate of 3% per year. In none of the patients, intraepithelial neoplasia nor an esophageal adenocarcinoma was detected. Logistic regression analysis identified endoscopic detection of islands or tongues as the only positive predictor of BE relapse (P= 0.0004). CONCLUSION: The long-term relapse rate of non neoplastic BE following complete ablation with high-power APC is low (3% per year).

Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease

Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated.Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials.However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation:(1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases(IBD).The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and(2) Species specific differences in the functionality of MSCs derived from mice versus humans.MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation.Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials.In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD.We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.

HNF-4α determines hepatic differentiation of human mesenchymal stem cells from bone marrow

AIM: To investigate the differentiation status and key factors to facilitate hepatic differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs). METHODS: Human MSCs derived from bone marrow were induced into hepatocyte-like cells following a previously published protocol. The differentiation status of the hepatocyte-like cells was compared with various human hepatoma cell lines. Overexpression of hepatocyte nuclear factor (HNF)-4α was mediated by adenovirus infection of these hepatocyte-like cells. The expression of interesting genes was then examined by either re-verse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods. RESULTS: Our results demonstrated that the differentiation status of hepatocyte-like cells induced from human MSCs was relatively similar to poorly differentiated human hepatoma cell lines. Interestingly, the HNF-4 isoform in induced MSCs and poorly differentiated human hepatoma cell lines was identified as HNF4γ instead of HNF-4α. Overexpression of HNF-4α in induced MSCs significantly enhanced the expression level of hepatic-specific genes, liver-enriched transcription factors, and cytochrome P450 (P450) genes. CONCLUSION: Overexpression of HNF-4α improves the hepatic differentiation of human MSCs from bone marrow and is a simple way of providing better cell sources for clinical applications.

Expression and clinical value of programmed cell death-ligand 1(PD-L1)in diffuse large B cell lymphoma:a retrospective study

Background: The programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1) pathway inhibits the activation of T cells and plays a crucial role in the negative regulation of cellular and humoral immune responses.Diffuse large B-cell lymphoma(DLBCL) is the most common lymphoid malignancy in adults. In the present study, we aimed to detect the expression of PD-L1 in DLBCL and to analyze its relationship with prognosis.Methods: We reviewed medical records of 204 newly diagnosed DLBCL patients in Sun Yat-sen University Cancer Center between October 2005 and August 2012. The expression of PD-L1 in tumor tissues from these 204 patients was detected using immunohistochemical(IHC) assay. The expression of anaplastic lymphoma kinase(ALK), CD5,CD30, and C-Myc in tumor specimens from 109 patients was detected using IHC, and Epstein-Barr virus(EBV)-encoded RNAs(EBERs) were detected using fluorescence in situ hybridization. The Spearman method was used for correlation analysis. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis.Results: Of the 204 patients, 100(49.0%) were PD-L1-positive in tumor cells and 44(21.6%) were PD-L1-positive in tumor microenvironment. PD-L1 expression in tumor cells and tumor microenvironment were more common in the non-germinal center B-cell-like(GCB) subtype than in the GCB subtype(P = 0.02 and P= 0.04). Patients with PD-L1 expression in tumor microenvironment were more likely to be resistant to first-line chemotherapy when compared with the patients without PD-L1 expression in tumor microenvironment(P = 0.03). PD-L1 expression in tumor microenvironment was negatively correlated with C-Myc expression(r =-0.20, P = 0.04). No correlations were detected between PD-L1 expression and the expression of ALK, CD5, and CD30 as well as EBERs. The 5-year overall survival(OS)rates were 50.0% and 67.3% in patients with and without PD-L1 expression in tumor cells(P = 0.02). PD-L1 expression in tumor cells was an independent risk predictor for OS(P < 0.01).Conclusions: PD-L1 expression is more common in the non-GCB subtype than in the GCB subtype. PD-L1 expression in tumor microenvironment has a negative correlation with C-Myc. PD-L1 positivity predicts short survival in DLBCL patients. For patients with PD-L1 expression, more strategy such as anti-PD-L1 antibody treatment should be recommended.

Endoscopic features and prognoses of mantle cell lymphoma with gastrointestinal involvement

AIM: To evaluate the endoscopic manifestations and prognoses of gastrointestinal (GI) mantle cell lymphoma (MCL). METHODS: A database search at the Department of Pathology of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences revealed 57 MCL patients with GI involvement. Clinical records were available for 35 of the 57 patients from 21 institutions, and those 35 patients were enrolled in this study. We summarized the gross types of endoscopic features, event-free survival (EFS), and overall survival (OS) of those patients.RESULTS: Of the 35 patients, GI involvement in the esophagus, stomach, and duodenum was found in 2 (5.7%), 26 (74.3%), and 12 (34.3%) patients, respectively. Twenty-one of the 35 patients underwent colonoscopy; among them, GI involvement in the ileum, cecum, colon, and rectum was found in 10 (47.6%), 3 (14.3%), 12 (57.1%), and 10 (47.6%), respectively. Various lesions, such as superficial, protruded, fold thickening, or ulcerative, were found in the stomach, whereas multiple lymphomatous polyposis (MLP) was dominant from the duodenum to the rectum. Twelve patients were treated with a hyper-CVAD/MA regimen, and they had better OS (3-year rate, 88.3% vs 46.4%, P < 0.01) and better EFS (3-year rate, 66.7% vs 33.8%, P < 0.05) than the remaining 23 patients who were not treated with this regimen. CONCLUSION: MLP was a representative form of intestinal involvement, whereas a variety of lesions were found in the stomach. The hyper-CVAD/MA regimen may improve survival in these patients.

Therapeutic implications of colon cancer stem cells

Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.

Diagnosis and treatment of hepatocellular carcinoma: An update

Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium "washout" in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and locoregional therapies(alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion's stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib.

Non-platinum-based chemotherapy for treatment of advanced gastric cancer:5-fluorouracil,taxanes,and irinotecan

Despite numerous advances in treatment options,advanced gastric cancer(AGC)remains a major public health issue and the leading cause of cancer-related deaths.Cisplatin is one of the most effective broadspectrum anticancer drugs for AGC and a doublet combination regimen of either cisplatin-based or 5-fluorouracil(5FU)-based chemotherapy is generally used for treatment of patients with AGC.However,there is still no consensus on the best regimen for treating AGC.Recently,various new chemotherapeutic agents,including oral 5FU,taxanes,and irinotecan,have been identified as improving the outcomes for AGC when used as a single agent or in combination with nonplatinum chemotherapy.Nonetheless,it is still unclear whether non-platinum-based chemotherapy is a viable treatment option for patients with AGC.Accordingly,this review focuses on the efficacy and tolerability of non-platinum-based chemotherapy for patients with AGC.

Addition of simvastatin to carvedilol non responders: A new pharmacological therapy for treatment of portal hypertension

AIMTo determine whether addition of simvastatin could be an important pharmacological rescue therapy for carvedilol non-responders. METHODSOne hundred and two consecutive patients of cirrhosis of liver with significant portal hypertension were included. Hepatic venous pressure gradient (HVPG) was measured at the base line and after proper optimization of dose; chronic response was assessed at 3 mo. Carvedilol non-responders were given simvastatin 20 mg per day (increased to 40 mg per day at day 15). Carvedilol plus simvastatin was continued for 1 mo and hemodynamic response was again measured at 1 mo. RESULTSA total of 102 patients with mean age of 58.3 ± 6.6 years were included. Mean baseline HVPG was 16.75 ± 2.12 mmHg and after optimization of dose and reassessment of HVPG at 3 mo, mean reduction of HVPG from baseline was 5.5 ± 1.7 mmHg and 2.8 ± 1.6 mmHg among responders and non-responders respectively (P CONCLUSIONAddition of simvastatin to carvedilol non-responders may prove to be an excellent rescue therapy in patients with portal hypertension.

Krüppel-like factors 4 and 5:the yin and yang regulators of cellular proliferation

Krüppel-like factors (KLFs) are evolutionarily conserved zinc finger-containing transcription factors with diverseregulatory functions in cell growth, proliferation, differentiation, and embryogenesis. KLF4 and KLF5 are two closelyrelated members of the KLF family that have a similar tissue distribution in embryos and adults. However, the two KLFsoften exhibit opposite effects on regulation of gene transcription, despite binding to similar, if not identical, cis-actingDNA sequences. In addition, KLF4 and 5 exert contrasting effects on cell proliferation in many instances; while KLF4is an inhibitor of cell growth, KLF5 stimulates proliferation. Here we review the biological properties and biochemicalmechanisms of action of the two KLFs in the context of growth regulation.