Influence of lactulose on interventional therapy for HCC patients with hepatocirrhosis and hypersplenism

Objective: To investigate the influence of lactulose on immunity of hepatocellular carcinoma(HCC) patients with hepatocirrhosis and hypersplenism after double-interventional therapies. Methods: A total of 40 HCC patients with hepatocirrhosis and hypersplenism, hospitalized during January 2013 to June 2014, were enrolled and randomized into control group and observation group. Both groups received partial splenic embolization combined with transcatheter arterial chemoembolization. Besides, observation group orally took lactulose 30 m L/d. Four days before interventional therapies and at day 1, 3, 7 and 14 after therapies, fasting venous blood was collected to detect white blood cell count, red blood cell count(RBC), and platelet count(PLT). Four days before therapies and at day 7 and 14 after therapies, the levels of alanine aminotransferase, aspartate transaminase, total bilirubin, malondialdehyde, super-oxide dismutase(SOD), IFN-α, and IL-4 as well as the distribution of T cell subsets in peripheral blood were tested. Complications were observed after interventional therapies. Results: Before interventional therapies the levels of white blood cell count, PLT and RBC in both groups showed no difference, while after interventional therapies the levels of PLT and RBC in both groups showed an increasing tendency(P<0.05). At day 14 after interventional therapies, the level of blood cell as well as that of SOD, IFN-α and IL-4 in serum were significantly higher than that before therapies; meanwhile, the levels of alanine aminotransferase and total bilirubin of observation group after therapies were significantly lower than before and control group(P<0.05), the levels of CD4+/CD8+, SOD and IFN-α were all higher than before and control group(P<0.05). Conclusions: Oral administration of lactulose could adjust the imbalance of oxidation system/antioxidant system in HCC patients with hepatocirrhosis and hypersplenism after interventional therapies, and improve the antitumor immunity and prognosis.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Optimizing care for gastric cancer with overt bleeding:Is systemic therapy a valid option?

Gastric cancer(GC)and gastroesophageal junction cancer(GEJC)represent a significant burden globally,with complications such as overt bleeding(OB)further exacerbating patient outcomes.A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB.Using propensity score matching,the study balanced the comparison groups to investigate overall survival and treatment-related adverse events.The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB,highlighting the complexities of treatment decisions in these high-risk patients.

Human induced pluripotent stem cell-derived therapies for regeneration after central nervous system injury

In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.

Synchronous splenectomy and hepatectomy for patients with hepatocellular carcinoma and hypersplenism:A casecontrol study

AIM:To investigate whether the use of synchronoushepatectomy and splenectomy(HS)is more effective than hepatectomy alone(HA)for patients with hepatocellular carcinoma(HCC)and hypersplenism.METHODS:From January 2007 to March 2013,84consecutive patients with HCC and hypersplenism who underwent synchronous hepatectomy and splenectomy in our center were compared with 84 well-matched patients from a pool of 268 patients who underwent hepatectomy alone.The short-term and longterm outcomes of the two groups were analyzed and compared.RESULTS:The mean time to recurrence was 21.11±12.04 mo in the HS group and 11.23±8.73 mo in the HA group,and these values were significantly different(P=0.001).The 1-,3-,5-,and 7-year disease-free survival rates for the patients in the HS group and the HA group were 86.7%,70.9%,52.7%,and 45.9%and 88.1%,59.4%,43.3%,and 39.5%,respectively(P=0.008).Platelet and white blood cell counts in the HS group were significantly increased compared with the HA group one day,one week,one month and one year postoperatively(P<0.001).Splenectomy and micro-vascular invasion were significant independent prognostic factors for disease-free survival.Gender,tumor number,and recurrence were independent prognostic factors for overall survival.CONCLUSION:Synchronous hepatectomy and hepatectomy potentially improves disease-free survival rates and alleviates hypersplenism without increasing the surgical risks for patients with HCC and hypersplenism.

Effect of partial splenic embolization on the immune function of cirrhosis patients with hypersplenism

Objective:To discover the effect of partial splenic embolization on the immune function of cirrhotic patients with hypersplenism.Methods:Patients involved in the study were enrolled and divided into three groups,including control group,experimental group,and complication group.Numbers of CD3^+,CD4^+ and CD8^+ T cells and CD4^+CD25^+CDl27^(low/-) Treg cells in the peripheral blood of patients before surgery,1 month,6 months,1 year,and 2 years after surgery were analyzed by fluorescence active cell sorting(FACS).Contents of immunoglobulins(IgA,IgG and IgM) were analyzed by auto immunoassay analyzer.Results:In the peripheral blood of patients from experimental group,numbers of CD3^+,CD4^+ and CD8^+ T cells initially declined,but afterwards increased to normal level;in the peripheral blood of patients from complication group,CD3^+ and CD8^+ T cells showed the same trend,but the number of CD4^+ T cells was below normal level at all detection times.Furthermore,CD3^+,CD4^+ and CD8^+ T cells in the peripheral blood of patients from complication group were initially less than those in experimental group,and afterwards were comparable between two groups.In patients from both experimental group and complication group,the number of CD4^+CD25^+CDl27^(low/-)Treg cells increased 1 month and 6 months after surgery,and gradually restored to normal level.CD4^+CD25^+CDl27^(low/-)Treg cell counts in patients from complication group were initially more than those in patients from experimental group 1 month and 6 months after surgery,but then they were comparable.Furthermore,contents of immunoglobulins(IgA,IgG and IgM) were comparable in three groups at all detection times.Conclusion:Partial splenic embolization influenced the immune function of cirrhotic patients with hypersplenism in the short term but the immune function could afterwards gradually restore to normal.Our results implicated that measures that prevent infection and improve immune function were necessary in early stage after undergoing PSE in order to reduce complications.

Surgical treatment for hepatocellular carcinoma and secondary hypersplenism

BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease with high mortality and serious effect on the life quality of patients. Operation is still the most effective treatment. Currently, in China, patients with HCC are often complicated by hepatitis B related liver cirrhosis and secondary hypersplenism. This study was undertaken to evaluate the effect and indications of synchronous hepatectomy and splenectomy for HCC patients with hypersplenism. METHODS: The clinical records and treating processes of 24 patients with HCC and hypersplenism during the period of January 1991 to July 2004 were analyzed retrospectively. RESULTS: Sixteen patients underwent hepatectomy and splenectomy, including extensive devascularizasion around the cardia (9 patients). Seven patients were treated with microwave ablation and splenectomy plus extensive esophagogastric devascularization. One patient underwent hepatectomy combined with microwave ablation and splenectomy plus extensive esophagogastric devascularization. There were no deaths during the operation. During the first week after operation, the symptoms of hypersplenism disappeared and the platelet (Plt) and white blood cell (WBC) counts were significantly elevated (Plt: 247×109/L vs. 45.9×109/L, WBC: 13.0×109/L vs.3.3×109/L,P<0.01). CONCLUSIONS: Synchronous splenectomy can increase the safety of hepatectomy in selected patients with HCC and secondary hypersplenism by reducing bleeding complications. Splenectomy enhances patients' immunity against tumor in a long period as well.

Partial embolization as re-treatment of hypersplenism after unsuccessful splenic artery ligation

Ligation of splenic artery(LSA) is used for the treatment of liver cirrhosis with hypersplenism. However, hypersplenism is not significantly improved following LSA treatment in some cases, and there are few reports of retreatment of hypersplenism after LSA. We report the case of a47-year-old man with liver cirrhosis and hypersplenism who underwent LSA treatment, but did not significantly improve. Laboratory tests revealed severe leukocytopeniaand thrombocytopenia. Celiac computed tomography arteriogram and digital subtraction angiography revealed two compensatory arteries connected to the hilar splenic artery from the left gastro-epiploic artery and from the dorsal pancreatic artery. Partial splenic embolization(PSE) was performed through the compensatory arteries. As a result, the patient achieved partial splenic ischemic infarction, and white blood cell and platelet counts rose and remained in the normal range. PSE is an effective therapeutic modality for the retreatment of hypersplenism when other modalities have failed.

Management of hypersplenism in non-cirrhotic portal hypertension:a surgical series

BACKGROUND:Hypersplenism is commonly seen in patients with non-cirrhotic portal hypertension(NCPH).While a splenectomy alone can effectively relieve the hypersplenism,it does not address the underlying portal hypertension.The present study was undertaken to analyze the impact of shunt and non-shunt operations on the resolution of hypersplenism in patients with NCPH.The relationship of symptomatic hypersplenism,severe hypersplenism and number of peripheral cell line defects to the severity of portal hypertension and outcome was also assessed.METHODS:A retrospective analysis of NCPH patients with hypersplenism managed surgically between 1999 and 2009 at our center was done.Of 252 patients with NCPH,64(45 with extrahepatic portal vein obstruction and 19 with non-cirrhotic portal fibrosis) had hypersplenism and constituted the study group.Statistical analysis was done using GraphPad InStat.Categorical and continuous variables were compared using the chi-square test,ANOVA,and Student’s t test.The MannWhitney U test and Kruskal-Wallis test were used to compare non-parametric variables.RESULTS:The mean age of patients in the study group was 21.81±6.1 years.Hypersplenism was symptomatic in 70.3% with an incidence of spontaneous bleeding at 26.5%,recurrent anemia at 34.4%,and recurrent infection at 29.7%.The mean duration of surgery was 4.16±1.9 hours,intraoperative blood loss was 457±126(50-2000) mL,and postoperative hospital stay 5.5±1.9 days.Following surgery,normalization of hypersplenism occurred in all patients.On long-term followup,none of the patients developed hepatic encephalopathy and 4 had a variceal re-bleeding(2 after a splenectomy alone,1 each after an esophago-gastric devascularization and proximal splenorenal shunt).Patients with severe hypersplenism and those with defects in all three peripheral blood cell lineages were older,had a longer duration of symptoms,and a higher incidence of variceal bleeding and postoperative morbidity.In addition,patients with triple cell line defects had elevated portal pressure(P=0.001),portal biliopathy(P=0.02),portal gastropathy(P=0.005) and intraoperative blood loss(P=0.001).CONCLUSIONS:Hypersplenism is effectively relieved by both shunt and non-shunt operations.A proximal splenorenal shunt not only relieves hypersplenism but also effectively addresses the potential complications of underlying portal hypertension and can be safely performed with good long-term outcome.Patients with hypersplenism who have defects in all three blood cell lineages have significantly elevated portal pressures and are at increased risk of complications of variceal bleeding,portal biliopathy and gastropathy.

Laparoscopic versus Traditional Open Splenectomy for Hepatocellular Carcinoma with Hypersplenism

This study aimed to examine the efficacy of the laparoscopic vs. traditional open splenectomy for hepatocellular carcinoma（HCC） with hypersplenism. Between 2002 and 2013, 51 Chinese HCC patients with hypersplenism underwent either simultaneous laparoscopic splenectomy plus anticancer therapies（Lap-S＆A）（n=25） or traditional open splenectomy plus anti-cancer therapies（TOS＆A）（n=26）. The outcomes were reviewed during and after the operation. Anti-cancer therapies for HCC included laparoscopic hepatectomy（LH） and laparoscopic microwave ablation（LMA）. The results showed that there was no significant difference in the operating time between the two groups, but the blood loss and blood transfusion were less, pain intensity after surgery was weaker, the time to first bowel movement, time to the first flatus and postoperative hospital stay were shorter, and the postoperative complication rate and the readmission rate were lower in the Lap-S＆A group than in the TO-S＆A group. Two patients in the Lap-S＆A group and one patient in the TO-S＆A group died 30 days after surgery. However, no significant difference in the mortality rate was noted between the two groups. It was concluded that simultaneous Lap-S＆A holds the advantages of more extensive indications, lower complication incidence and less operative expenditure than conventional open approach and it is a feasible and safe approach for HCC with hypersplenism.

Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension

Since the first laparoscopic splenectomy(LS)was reported in 1991,LS has become the gold standard for the removal of normal to moderately enlarged spleens in benign conditions.Compared with open splenectomy,fewer postsurgical complications and better postoperative recovery have been observed,but LS is contraindicated for hypersplenism secondary to liver cirrhosis in many institutions owing to technical difficulties associated with splenomegaly,well-developed collateral circulation,and increased risk of bleeding.With the improvements of laparoscopic technique,the concept is changing.This article aims to give an overview of the latest development in laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension.Despite a lack of randomized controlled trial,the publications obtained have shown that with meticulous surgical techniques and advanced instruments,LS is a technically feasible,safe,and effective procedure for hypersplenism secondary to cirrhosis and portal hypertension and contributes to decreased blood loss,shorter hospital stay,and less impairment of liver function.It is recommended that the dilated short gastric vessels and other enlarged collateral circulation surrounding the spleen be divided with the LigaSure vessel sealing equipment,and the splenic artery and vein be transected en bloc with the application of the endovascular stapler.To support the clinical evidence,further randomized controlled trials about this topic are necessary.

Comparison of total splenic artery embolization and partial splenic embolization for hypersplenism

AIM:To evaluate whether total splenic artery embolization(TSAE) for patients with hypersplenism delivers better long-term outcomes than partial splenic embolization(PSE).METHODS:Sixty-one patients with hypersplenism eligible for TSAE(n = 27,group A) or PSE(n = 34,group B) were enrolled into the trial,which included clinical and computed tomography follow-up.Data on technical success,length of hospital stay,white blood cell(WBC) and platelet(PLT) counts,splenic volume and complications were collected at 2 wk,6 mo,and 1,2,3,4 years postoperatively.RESULTS:Both TSAE and PSE were technically successful in all patients.Complications were significantly fewer(P = 0.001),and hospital stay significantly shorter(P = 0.007),in group A than in group B.Postprocedure WBC and PLT counts in group A were significantly higher than those in group B from 6 mo to 4 years(P = 0.001),and post-procedure residual splenic volume in group A was significantly less than that observed in group B at 1,2,3 and 4 years post-procedure(P = 0.001).No significant differences were observed in red blood cell counts and liver function parameters between the two groups following the procedure.CONCLUSION:Our results indicate that TSAE for patients with hypersplenism not only delivers a better longterm outcome,but is also associated with lower complication rates and a shorter hospital stay than PSE.

Total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism

AIM:To study the safety and feasibility of total embolization of the main splenic artery as a supplemental treatment modality for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver cirrhosis.METHODS:Fifteen consecutive patients with hypersplenism due to cirrhosis were enrolled in this study from January 2006 to June 2010.All patients underwent total embolization of the main splenic artery.Clinical symptoms,white blood cell(WBC) and platelet(PLT) counts,splenic volume,and complications of the patients were recorded.The patients were followed up for 1 and 6 mo,and 1,2,3 years,respectively,after operation.RESULTS:Total embolization of the main splenic artery was technically successful in all patients.Minor complications occurred in 13 patients after the procedure,but no major complications were found.The WBC andPLT counts were significantly higher and the residual splenic volume was significantly lower 1 and 6 mo,and 1,2,3 years after the procedure than before the procedure(P < 0.01).Moreover,the residual splenic volume increased very slowly with the time after embolization.All patients were alive during the follow-up period.CONCLUSION:Total embolization of the main splenic artery is a safe and feasible procedure and may serve as a supplemental treatment modality for hypersplenism with thrombocytopenia or leukocytopenia accompanying liver cirrhosis.

Radiofrequency ablation for treatment of hypersplenism: A feasible therapeutic option

We present a case of a patient with hypersplenism secondary to portal hypertension due to hepato-splenic schistosomiasis, which was accompanied by severe and refractory thrombocytopenia. We performed spleen ablation and measured the total spleen and ablated volumes with contrast-enhanced computed tomography and volumetry. No major complications occurred, thrombocytopenia was resolved, and platelet levels remained stable, which allowed for early treatment of the patient's underlying disease. Previous work has shown that splenic radiofrequency ablation is an attractive alternative treatment for hypersplenism induced by liver cirrhosis. We aimed to contribute to the currently sparse literature evaluating the role of radiofrequency ablation(RFA) in the management of hypersplenism. We conclude that splenic RFA appears to be a viable and promising option for the treatment of hypersplenism.

Simultaneous partial splenectomy during liver transplantation for advanced cirrhosis patients combined with severe splenomegaly and hypersplenism

BACKGROUND The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation(LT).However,splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly.AIM To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism.METHODS Between October 2015 and February 2019,762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital.Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism.Among these patients,41 received partial splenectomy during LT(PSLT group),and 43 received only LT(LT group).Patient characteristics,intraoperative parameters,and postoperative outcomes were retrospectively analyzed and compared between the two groups.RESULTS The incidence of postoperative hypersplenism(2/41,4.8%)and recurrent ascites(1/41,2.4%)in the PSLT group was significantly lower than that in the LT group(22/43,51.2%;8/43,18.6%,respectively).Seventeen patients(17/43,39.5%)in the LT group required two-stage splenic embolization,and further splenectomy was required in 6 of them.The operation time and intraoperative blood loss in the PSLT group(8.6±1.3 h;640.8±347.3 mL)were relatively increased compared with the LT group(6.8±0.9 h;349.4±116.1 mL).The incidence of postoperative bleeding,pulmonary infection,thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group,respectively.CONCLUSION Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.

Treatment modalities for hypersplenism in liver transplant recipients with recurrent hepatitis C

Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft and patient survival. The combination therapy of interferon and ribavirin has been shown to be the most effective therapy for recurrent hepatitis C. However, pre-and post-transplant hypersplenism often precludes patients from receiving the antiviral therapy. Splenectomy and partial splenic embolization are the two invasive modalities that can correct the cytopenia associated with hypersplenism. In this report we review the two treatment options, their associated outcomes and complications.

Neoadjuvant therapy for pancreas cancer: Past lessons and future therapies

Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.

Value of portal hemodynamics and hypersplenism in cirrhosis staging

AIM: To determine the correlation between portal hemodynamics and spleen function among different grades of cirrhosis and verify its significance in cirrhosis staging.METHODS: The portal and splenic vein hemodynamics and spleen size were investigated by ultrasonography in consecutive 38 cirrhotic patients with cirrhosis (Child's grades A to C) and 20 normal controls. The differences were compared in portal vein diameter and flow velocity between patients with and without ascites and between patients with mild and severe esophageal varices. The correlation between peripheral blood cell counts and Child's grades was also determined.RESULTS: The portal flow velocity and volume were significantly lower in patients with Child's C (12.25±1.67 cm/s vs 788.59±234 mm/min, respectively) cirrhosis compared to controls (19.55±3.28 cm/s vs 1254.03±410 mm/min,respectively) and those with Child's A (18.5±3.02 cm/s vs1358.48±384 mm/min, respectively) and Child's B (16.0±3.89cm/s vs 1142.23±390 mm/min, respectively)cirrhosis.Patients with ascites had much lower portal flow velocity and volume (13.0±1.72 cm/s vs 1078±533 mm/min) than those without ascites (18.6±2.60 cm/s vs 1394±354 mm/min).There was no statistical difference between patients with mild and severe esophageal varices. The portal vein diameter was not significantly different among the above groups.There were significant differences in splenic vein diameter,flow velocity and white blood cell count, but not in spleen size, red blood cell and platelet counts among the various grades of cirrhosis. The spleen size was negatively correlated with red blood cell and platelet counts (r= -0.620and r = -0.8.34, respectively).CONCLUSION: An optimal system that includes parameters representing the portal hemodynamics and spleen function should be proposed for cirrhosis staging.

When combination therapy isn't working: Emerging therapies for the management of inflammatory bowel disease

Although antagonists of tumor necrosis factor have resulted in major therapeutic benefits in inflammatory bowel disease, the magnitude and durability of response are variable. Similar to previously available drugs such as 5-aminosalicylates and immunomodulators, the therapeutic effect is not universal leaving many people searching for options. The development of newer agents has benefited from advances in the understanding of the pathophysiology of the disease. Uncontrolled activation of the acquired immune system has an important role, and lymphocytes, cytokines, and adhesion molecules are broadly targeted for therapeutic intervention. There is increasing evidence of an important role of the innate immune system and the intestinal epithelium, and the therapeutic paradigm is also shifting from immunosuppression to the reinforcement of the intestinal barrier, and modification of the disease process. In this review, we explore the limitation of current therapy as well as mechanisms of actions of new drugs and the efficacy and adverse events from data from clinical trials.

Loco-regional therapies for patients with hepatocellular carcinoma awaiting liver transplantation: Selecting an optimal therapy

Hepatocellular carcinoma(HCC) is a common, increasingly prevalent malignancy. For all but the smallest lesions, surgical removal of cancer via resection or liver transplantation(LT) is considered the most feasible pathway to cure. Resection- even with favorable survival- is associated with a fairly high rate of recurrence, perhaps since most HCCs occur in the setting of cirrhosis. LT offers the advantage of removing not only the cancer but the diseased liver from which the cancer has arisen, and LT outperforms resection for survival with selected patients. Since time waiting for LT is time during which HCC can progress, locoregional therapy(LRT) is widely employed by transplant centers. The purpose of LRT is either to bridge patients to LT by preventing progression and waitlist dropout, or to downstage patients who slightly exceed standard eligibility criteria initially but can fall within it after treatment. Transarterial chemoembolization and radiofrequency ablation have been the most widely utilized LRTs to date, with favorable efficacy and safety as a bridge to LT(and for the former, as a downstaging modality). The list of potentially effective LRTs has expanded in recent years, and includes transarterial chemoembolization with drug-eluting beads, radioembolization and novel forms of extracorporal therapy. Herein we appraise the various LRT modalities for HCC, and their potential roles in specific clinical scenarios in patients awaiting LT.