Shear wave velocity is a useful marker for managing nonalcoholic steatohepatitis

AIM:To investigate whether a noninvasive measurement of tissue strain has a potential usefulness for management of nonalcoholic steatohepatitis(NASH).METHODS:In total 26 patients,23 NASHs and 3 normal controls were enrolled in this study.NASH was staged based on Brunt criterion.At a region of interest(ROI),a shear wave was evoked by implementing an acoustic radiation force impulse(ARFI),and the propagation velocity was quantif ied.RESULTS:Shear wave velocity(SWV) could be reproducibly quantified at all ROIs in all subjects except for 4 NASH cases,in which a reliable SWV value was not calculated at several ROIs.An average SWV of 1.34 ± 0.26 m/s in fibrous stage 0-1 was significantly slower than 2.20 ± 0.74 m/s and 2.90 ± 1.01 m/s in stages 3 and 4,respectively,but was not significantly different from 1.79 ± 0.78 m/s in stage 2.When a cutoff value was set at 1.47 m/s,receiver operating characteristic analysis showed significance to dissociate stages 3 and 4 from stage 0-1(P=0.0092) with sensitivity,specificity and area under curve of 100%,75% and 94.2%,respectively.In addition,the correlation between SWV and hyaluronic acid was significant(P<0.0001),while a tendency toward negative correlation was observed with serum albumin(P=0.053).CONCLUSION:The clinical implementation of ARFI provides noninvasive repeated evaluations of liver stiffness at an arbitrary position,which has the potential to shed new light on NASH management.

Natural regression of fibrosis in chronic hepatitis B

The fibrosis of liver cirrhosis was considered to be irreversible before the anti-viral drugs showed that it is reversible when they lead to continuous suppression of viral replication and inflammation. However, several reports previously showed that fibrosis of type B liver cirrhosis was almost completely absorbed after the natural remission of chronic inflammation. This phenomenon might not be limited to exceptional patients, but rather occur commonly, considering the dynamic clinical features of chronic hepatitis B(CHB), where inactive carrier stage normally follows aggravation of hepatitis and progression of fibrosis at the time of HBe Ag seroconversion. Thus, fibrosis levels of CHB as a hepatocellular carcinoma(HCC)-surveillance marker, particularly those of the inactive stage, could be underestimated, because some of them might have been(pre)cirrhotic in the past and recovered with the natural regression of fibrosis. We argue that cirrhosisinduced HCC mechanisms, rather than direct action of viral genome, may be more common than generally considered in CHB patients. This may have some impact on reconsidering the surveillance rationale for HCC in CHB, from where advanced HCCs tended to be missed. In addition, a molecular marker to assess the cancer-prone characteristics of the liver will definitely be needed to resolve the issue.

Impact of metastatic lymph node ratio in node-positive colorectal cancer

Colorectal cancer(CRC) is one of the most common malignant diseases in the world.Presently,the most widely used staging system for CRC is the tumor nodes metastasis classification system,which classifies patients into prognostic groups according to the depth of the primary tumor,presence of regional lymph node(LN) metastases,and evidence of distant metastatic spread.The number of LNs with confirmed metastasis is related to the severity of the disease,but this number depends on the number of LNs retrieved,which varies depending on patient age,tumor grade,surgical extent,and tumor site.Numerous studies and a recent structured review have demonstrated associated improvements in the survival of CRC patients with increasing numbers of LNs retrieved for examination.Hence,the impact of lymph node ratio(LNR),defined as the number of metastatic LNs divided by the number of LNs retrieved,has been investigated in various malignancies,including CRC.In this editorial,we review the literature demonstrating the clinicopathological significance of LNR in CRC pati-ents.Some reports have indicated the advantage of considering the LNR compared to the number of LNs retrieved and/or LN status.When the LNR is taken into consideration for survival analysis,the number of LNs retrieved and/or the LN status is not always found to be a prognostic factor.The cut-off points for LNRs were proposed in numerous studies.However,optimal thresholds for LNRs have not yet received consensus.It is still unclear whether the LNR has more prognostic validity than N stage.For all these reasons,the potential advantages of LNRs in the staging system should be investigated in large prospective data sets.

Oncogenic role of p21 in hepatocarcinogenesis suggests a new treatment strategy

A well-known tumor suppressor, p21, acts parado-xically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinogenesis. The molecular behavior of p21 depends on its subcellular localization. Nuclear p21 may inhibit cell proliferation and be proapoptotic, while cytoplasmic p21 may have oncogenic and anti-apoptotic functions. Because most typical tumor suppressive proteins also have different effects according to subcellular localization, elucidating the regulatory mechanisms underlying nucleo-cytoplasmic transport of these proteins would be significant and may lead to a new strategy for anti-hepatocellular carcinoma(HCC) therapy. Chromosome region maintenance 1(CRM1) is a major nuclear export receptor involved in transport of tumor suppressors from nucleus to cytoplasm. Expression of CRM1 is enhanced in a variety of malignancies and in vitro studies have shown the efficacy of specific inhibition of CRM1 against cancer cell lines. Interestingly, interferon may keep p21 in the nucleus; this is one of the mechanisms of its anti-hepatocarcinogenic function. Here we review the oncogenic property of p21, which depends on its subcellular localization, and discuss the rationale underlying a new strategy for HCC treatment and prevention.

Successful embolization assisted by covered stents for a pseudoaneurysm following pancreatic surgery

Delayed intra-abdominal hemorrhage after pancreatic surgery is a potentially lethal complication.Transarterial coil embolization and/or the placing of an endovascular stent are minimally invasive and effective procedures.An artery that is extensively eroded and rendered friable due to operative skeletonization or postoperative inflammation sometimes contributes to delayed intra-abdominal hemorrhage or rebleeding after coil embolization.This report presents a case of successful management of postoperative hemorrhage in a-74-year-old Japanese male.He experienced bleeding from a pseudoaneurysm of the brittle hepatic artery following total pancreatectomy.Initially the pseudoaneurysm was successfully treated with covered coronary stent-grafts,but rebleeding occurred 1 mo later due to the brittleness of the artery.Rebleeding was definitively managed by the complete packing of the stent by coil embolization.He remains stable at 18 mo following the f inal embolization.A stent graft can be used for protecting a brittle artery to avoid injury by coil embolization.

Single-incision laparoscopic cecectomy for low-grade appendiceal mucinous neoplasm after laparoscopic rectectomy

In this case report,we discuss single-incision laparoscopic cecectomy for low-grade appendiceal neoplasm after laparoscopic anterior resection for rectal cancer.The optimal surgical therapy for low-grade appendiceal neoplasm is controversial;currently,the options include appendectomy,cecectomy,right hemicolectomy,and open or laparoscopic surgery.Due to the risk of pseudomyxoma peritonei,complete resection without rupture is necessary.We have encountered 5 cases of lowgrade appendiceal neoplasm and all 5 patients had no lymph node metastasis.We chose the appendectomy or cecectomy without lymph node dissection if preoperative imaging studies did not suspect malignancy.In the present case,we performed cecectomy without lymph node dissection by single-incision laparoscopic surgery(SILS),which is reported to be a reduced port surgery associated with decreased invasiveness and patient stress compared with conventional laparoscopic surgery.We are confident that SILS is a feasible alternative to traditional surgical procedures for borderline tumors,such as low-grade appendiceal neoplasms.

Efficacy of subcutaneous penrose drains for surgical site infections in colorectal surgery

AIM: To investigate whether a subcutaneous penrose drain would decrease the superficial surgical site infection (s-SSI) rate in elective colorectal surgery. METHODS: This is a comparative study of the historical control type. Intervention consisted of the use of penrose drain in elective open colorectal surgical wounds. The outcome was an incidence of s-SSI. The patients were risk stratified according to the depth of subcutaneous tissue.RESULTS: There were 131 patients (40 patients with high s-SSI risk) in the prior period (from July 2008 to June 2009, when no penrose drains were inserted) and 151 patients (75 patients with high s-SSI risk) in the latter period (from June 2010 to November 2011, when penrose drains were inserted). The overall s-SSI rate was 6.1% and 5.3% during the two periods (P = 0.770), and the s-SSI rate in the high s-SSI risk group was 15.0% and 8.0% (P = 0.242).CONCLUSION: Although penrose drain was not observed to significantly reduce s-SSI, there tended to be a reduced risk of s-SSI in the high s-SSI risk group.

Solitary mediastinal lymph node recurrence after curative resection of colon cancer

We report two cases of solitary mediastinal lymph node recurrence after colon cancer resection. Both cases had para-aortic lymph node metastasis at the time of initial surgery and received adjuvant chemotherapy for 4 years in case 1 and 18 mo in case 2. The time to recurrence was more than 8 years in both cases. After resection of the recurrent tumor, the patient is doing well with no recurrence for 6 years in case 1 and 4 mo in case 2. Patients should be followed up after colon cancer surgery considering the possibility of solitary mediastinal lymph node recurrence if they had para-aortic node metastasis at the time of initial surgery.

Contributions of transgenic mouse studies on the research of hepatitis B virus and hepatitis C virus-induced hepatocarcinogenesis

Transgenic mouse technology has enabled the investigation of the pathogenic effects, including those on development, immunological reactions and carcinogenesis, of viral genes directly in living organism in a real-time manner. Although viral hepatocarcinogenesis comprises multiple sequences of pathological events, that is, chronic necroinflammation and the subsequent regeneration of hepatocytes that induces the accumulation of genetic alterations and hepatocellular carcinoma(HCC), the direct action of viral proteins also play significant roles. The pathogenesis of hepatitis B virus X and hepatitis C virus(HCV) core genes has been extensively studied by virtue of their functions as a transactivator and a steatosis inducer, respectively. In particular, the mechanism of steatosis in HCV infection and its possible association with HCC has been well studied using HCV core gene transgenic mouse models. Although transgenic mouse models have remarkable advantages, they are intrinsically accompanied by some drawbacks when used to study human diseases. Therefore, the results obtained from transgenic mouse studies should be carefully interpreted in the context of whether or not they are well associated with human pathogenesis.

Standardized technique for single-incision laparoscopicassisted stoma creation

To describe the procedure, efficacy, and utility of singleincision laparoscopic-assisted stoma creation(SILStoma) for transverse colostomy. Using single-incision laparoscopic surgery, we developed a standardized technique for SILStoma. Twelve consecutive patients underwent SILStoma for transverse colostomy at Osaka Medical Center for Cancer and Cardiovascular Diseases from April 2013 to March 2016. A single, intended stoma site was created with a 2.5-3.5 cm skin incision for primary access to the intra-abdominal space, and it functioned as the main port through which multi-trocars were placed. Clinical and operative factors and postoperative outcomes were evaluated. Patient demographics, including age, gender, body mass index, and surgical indications for intestinal diversion were evaluated. SILStoma was performed in nine cases without the requirement of additional ports. In the remaining three cases, 1-2 additional 5-mm ports were required for mobilization of the transverse colon and safe dissection of abdominal adhesions. No cases required conversion to open surgery. In all cases, SILStoma was completed at the initial stoma site marked preoperatively. No intraoperative or postoperative complications greater than Grade Ⅱ(the Clavien-Dindo classification) were reported in the complication survey. Surgical site infection at stoma sites was observed in four cases; however, surgical interventions were not required and all infectionswere cured completely. In all cases, the resumption of bowel movements was observed between postoperative days 1 and 2. SILStoma for transverse loop colostomy represents a feasible surgical procedure that allows the creation of a stoma at the preoperatively marked site without any additional large skin incisions.

Multicentric occurrence of hepatocellular carcinoma with nonalcoholic steatohepatitis

AIM:To reveal the manner of hepatocellular carcinoma (HCC) development in patients with nonalcoholic steatohepatitis(NASH) focusing on multicentric occurrence (MO) of HCC.METHODS:We compared clinicopathological characteristics between patients with and without MO of HCC arising from NASH background.The clinical features were implicated with reference to the literature available.RESULTS:MO of HCC was identified with histological proof in 4 out of 12 patients with NASH-related HCC(2 males and 2 females).One patient had synchronous MO;an advanced HCC,two well-differentiated HCCs and a dysplastic nodule,followed by the development of metachronous MO of HCC.The other three patients had multiple advanced HCCs accompanied by a well-differentiated HCC or a dysplastic nodule.Of these three patients,one had synchronous MO,one had metachronous MO and the other had both synchronous and metachronous MO.There were no obvious differences between the patients with or without MO in terms of liver function tests,tumor markers and anatomical extent of HCC.On the other hand,all four patients with MO of HCC were older than 70 years old and had the comorbidities of obesity,type 2 diabetes mellitus(T2DM),hypertension and cirrhosis.Although these conditions were not limited to MO of HCC,all the conditions were met in only one of eight patients without MO of HCC.Thus,concurrence of these conditions may be a predisposing situation to synchronous MO of HCC.In particular,old age,T2DM and cirrhosis were suggested to be prerequisite for MO because these factors were depicted in common among two other cases with MO of HCC under NASH in the literature.CONCLUSION:The putative predisposing factors and necessary preconditions for synchronous MO of HCC in NASH were suggested in this study.Further investigations are required to clarify the accurate prevalence and predictors of MO to establish better strategies for treatment and prevention leading to the prognostic improvement in NASH.