Underwater endoscopic mucosal resection: a new endoscopic method for resection of rectal neuroendocrine tumor grade 1 (carcinoid) ≤ 10 mm in diameter.

Background and study aims Rectal neuroendocrine tumors grade 1 (NET G1; carcinoid) ≤ 10 mm in diameter often extend into the submucosa, making their complete histological resection difficult using endoscopic techniques. Endoscopic submucosal resection with a ligation device (ESMR-L) and endoscopic submucosal dissection (ESD) are commonly used to overcome these difficulties. We also previously reported that underwater endoscopic mucosal resection (UEMR) could facilitate resection of rectal NET G1. This study aimed to evaluate the safety and efficacy of UEMR for removing rectal NET G1 ≤ 10 mm in diameter. 6 consecutive patients with rectal NET G1 ≤ 10 mm in diameter underwent UEMR at our hospital. The rate of en bloc resection was 100 %, and the rate of R0 resection was 83 %. The median procedure time was 8 min (range 5 - 12 min). No perforations or delayed bleeding occurred in this study. In conclusion, UEMR allows the safe and reliable resection of rectal NET G1 ≤ 10 mm in diameter with comparable results to ESMR-L or ESD, including high en bloc and R0 resection rates with no increase in significant adverse events. A multicenter trial is required to confirm the validity of the present results.

Cold snare polypectomy reduced delayed postpolypectomy bleeding compared with conventional hot polypectomy: a propensity score-matching analysis.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) for small colorectal polyps has lower incidence of adverse events, especially delayed postpolypectomy bleeding (DPPB). However, few data are available on comparisons of the incidence of DPPB of CSP and hot polypectomy (HP). The aim of this study was to evaluate the incidence of DPPB after CSP and compare it with that of HP. A propensity score model was used as a secondary analysis. PATIENTS AND METHODS: This was a retrospective cohort study conducted in a single municipal hospital. We identified 539 patients with colorectal polyps from 2 mm to 11 mm in size who underwent CSP (804 polyps in 330 patients) or HP (530 polyps in 209 patients) between July 2013 and June 2015. RESULTS: There were no cases of DPPB in the CSP group. Conversely, DPPB occurred in 4 patients (1.9 %) after HP, resulting in a significant difference between the CSP and HP groups (0.008 % vs 0 %, P  = 0.02). Propensity score-matching analysis created 402 matched pairs, yielding a significantly higher DPPB rate in the HP group than CSP group (0.02 % vs 0 %, P  = 0.04). However, significantly more patients in the CSP group had unclear horizontal margins that precluded assessment (83 vs 38 cases, P  < 0.001). The retrieval failure rate was significantly higher in the CSP group than in the HP group (3 % vs 0.7 %, P  = 0.01). CONCLUSIONS: DPPB was less frequent with CSP than HP, as selected by the propensity score-matching model. Our findings indicate that CSP is recommended polypectomy in daily clinical setting. However, special care should be taken during polyp retrieval and horizontal margin assessment, and these issues could be taken into account in follow-up after CSP.

Gastric atrophy and xanthelasma are markers for predicting the development of early gastric cancer.

BACKGROUND: The significance of gastric xanthelasma in relation to gastric cancer still remains unclear. We investigated whether gastric xanthelasma would be a useful marker for predicting the development of early gastric cancer. METHODS: A total of 1823 patients who underwent a medical health checkup were enrolled. We examined the relationship between gastric xanthelasma and various clinical features, and in an endoscopic follow-up study investigated whether the presence of gastric xanthelasma was predictive of the development of early gastric cancer. RESULTS: In the initial endoscopic examination, gastric xanthelasma was detected in 107 (5.9 %) of the 1823 patients. The presence of gastric xanthelasma was significantly associated with age ≥65 years, male gender, open-type atrophy, and the presence of diabetes mellitus (DM) (p < 0.0001, p < 0.0001, p < 0.0001, and p < 0.0001, respectively). During the endoscopic follow-up period, early gastric cancer was found in 29 (1.6 %) of the 1823 patients. Gastric cancer occurred in 15 (14.0 %) of 107 patients with gastric xanthelasma, whereas it occurred in 14 (0.8 %) of 1716 patients without (p < 0.0001). Multivariate analysis revealed that open-type atrophy and gastric xanthelasma were independently related to the development of gastric cancer (odds ratio 7.19 [2.50-20.83]; p = 0.0003 and 5.85 [2.67-12.82]; p < 0.0001, respectively). The presence of gastric xanthelasma was significantly predictive of gastric cancer development even in the selected high-risk groups with open-type atrophy or DM (p < 0.0001 or p < 0.0001, respectively). CONCLUSIONS: Gastric xanthelasma is a useful marker for predicting the development of gastric cancer.

Clinical characteristics of collagenous colitis with linear ulcerations.

BACKGROUND: The relationship between the thickness of subepithelial collagen bands (CB) and the development of linear ulcerations (LU) in collagenous colitis (CC) remains unclear. The aim of the present study was to compare the clinical and pathological features, including the thickness of CB, in CC patients with and without LU. PATIENTS AND METHODS: Twenty-five patients with CC diagnosed by pathological examination of biopsy specimens were analyzed. Eleven patients with LU (LU group) and 14 patients without LU (non-LU group) were compared. RESULTS: Ten patients in the LU group and seven in the non-LU group were taking lansoprazole (P = 0.038). Seven patients in the LU group and one in the non-LU group were taking non-steroidal anti-inflammatory drugs (NSAIDs) (P = 0.004). All LU were locatedin the transverse or left colon. Patients in the LU group were older than those in the non-LU group (P = 0.015). CB were significantly thicker in the LU group than in the non-LU group (mean ± SD, 40 ± 21 µm vs 20 ± 11 µm, P = 0.004). Multivariate analysis showed that NSAIDs use (odds ratio, 19.236; 95% confidence interval, 1.341-275.869) and CB thickness (odds ratio, 0.893; 95% confidence interval, 0.804-0.999) were independently associated with the development of LU. CONCLUSION: Use of lansoprazole and NSAIDs, thick CB, and advanced age are associated with the development of LU in CC patients.

The effect of long-term supplementation with branched-chain amino acid granules in patients with hepatitis C virus-related hepatocellular carcinoma after radiofrequency thermal ablation.

GOALS: To elucidate whether long-term supplementation with branched-chain amino acid (BCAA) granules improves overall survival (OS) and recurrence-free survival (RFS) after radiofrequency thermal ablation (RFA) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of ≤3.5 g/dL. BACKGROUND: Whether BCAA treatment after curative RFA for patients with HCV-related HCC improves OS and RFS remains unclear. STUDY: We compared the OS rate and the RFS rate between the BCAA group (n=115) and the control group (n=141). We also examined factors contributing to OS and RFS. RESULTS: The 1 and 3 years OS rates after RFA were 94.0% and 70.0%, respectively, in the BCAA group, and 94.0% and 49.8%, respectively, in the control group (P=0.001). The corresponding RFS rates 1 and 3 years after RFA were 61.8% and 28.0%, respectively, in the BCAA group, and 52.0% and 12.0%, respectively, in the control group (P=0.013). In the multivariate analysis, in terms of OS, BCAA treatment, and serum albumin level of ≥3.4 g/dL, and in terms of RFS, age 70 years or older, BCAA treatment, and a serum albumin level of ≥3.4 g/dL were significant independent factors, respectively. CONCLUSIONS: BCAA treatment may improve OS and RFS after RFA in patients with HCV-related HCC≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of 3.5 g/dL.

Impact of pretreatment serum cholinesterase level in unresectable advanced hepatocellular carcinoma patients treated with sorafenib.

The value of serum cholinesterase (ChE) level as a predictive marker in sorafenib therapy for advanced hepatocellular carcinoma (HCC) has not yet been investigated. The present retrospective study therefore analyzed the impact of the serum ChE level in 93 patients with advanced HCC treated with sorafenib. Patients were categorized into two groups: group A with pretreatment serum ChE ≥140 IU/l (n=46) and group B with pretreatment serum ChE <140 IU/l (n=47). The correlation between clinicopathological findings, including serum ChE level, and overall survival (OS) and liver damage during sorafenib therapy was investigated. The median OS of the patients was 275 days, while OS was markedly higher in group A compared to group B (P=0.002). In 70 Child-Pugh A patients, serum ChE level was a significant prognostic predictor in multivariate analysis [P=0.019, hazard ratio (HR) =2.612; 95% confidence interval (CI), 1.174-5.810]. During sorafenib treatment, 22 patients developed liver dysfunction of grade 3 or higher. Only two group A patients (4.3%) developed liver dysfunction, compared to 20 group B patients (42.6%) (P<0.001). Multivariate analysis demonstrated that the pretreatment serum ChE level was the strongest predictor of liver damage (P=0.002, HR=0.061, 95% CI: 0.010-0.373), indicating serum ChE <140 IU/l to be the only independent predictor associated with severe liver function damage during sorafenib treatment in 70 patients with grade A Child-Pugh (P= 0.016; HR= 0.122; 95% CI, 0.022-0.676). In conclusion, lower serum ChE level is a significant predictor of poor prognosis and severe liver damage in HCC patients treated with sorafenib. Advanced HCC patients with lower serum ChE levels, including those with a Child-Pugh A pretreatment liver function score, should be given sorafenib therapy with caution.

Percutaneous radiofrequency ablation for hepatocellular carcinoma: clinical outcome and safety in elderly patients.

BACKGROUND AND AIMS: We aimed to compare clinical outcomes and safety of radiofrequency ablation (RFA) in single hepatocellular carcinoma (HCC) patients aged > 75 years (elderly group) versus patients aged < 75 years (control group). PATIENTS AND METHODS: There were 130 patients in the elderly group and 238 in the control group. Clinical outcomes including overall survival (OS), recurrence free survival (RFS) and local tumor progression (LTP), and safety were analysed for these two groups after initial RFA. RESULTS: The mean (+/- standard deviation [SD]) tumor diameter in the elderly and the control groups was 2.13 +/- 0.86 cm and 1.92 +/- 0.63 cm, respectively; the mean (+/- SD) observation period was 2.5 +/- 1.8 years and 3.2 +/- 2.0 years, respectively. The 1 and 3 year OS rates were 90.0 and 64.1%, respectively, in the elderly group and 97.6 and 83.7%, respectively, in the control group (P=0.001); the corresponding RFS rates were 66.9 and 21.3%, respectively, in the elderly group and 80.5 and 40.0%, respectively, in the control group (P=0.001). The 1 and 3 year LTP rates were 15.0 and 43.0%, respectively, in the elderly group and 8.3 and 26.3%, respectively, in the control group (P=0.002). In terms of duration of hospitalization (P=0.807) and serious adverse events related RFA (P=0.670), there was no significant difference between these two groups. CONCLUSION: The clinical outcomes in the elderly group were poorer than those in the control group, although RFA in the elderly patients was a safe procedure.

Comparison of the efficacy of transcatheter arterial chemoembolization and sorafenib for advanced hepatocellular carcinoma.

The aim of the present study was to compare overall survival between stage IVA or stage IVB hepatocellular carcinoma (HCC) patients who received transcatheter arterial chemoembolization (TACE) and those who were treated with sorafenib. This retrospective comparative study included 55 patients with stage IVA or IVB HCC in whom TACE was performed as an initial treatment (the TACE group) and 56 patients with stage IVA or IVB HCC to whom sorafenib was administered (the sorafenib group). We compared the overall survival between these two groups. In the TACE group, there were 46 stage IVA HCC patients and 9 stage IVB HCC patients. In the sorafenib group, there were 26 stage IVA HCC patients and 30 stage IVB HCC patients. Median overall survival times were 6.6 months in the TACE group and 9.2 months in the sorafenib group. The 1- and 2-year overall survival rates were 34.4 and 14.2%, respectively, in the TACE group and 34.0 and 6.7%, respectively, in the sorafenib group. In terms of overall survival, there was no significant difference between the two groups (P=0.814). In subgroup analyses, according to HCC stage [stage IVA (P=0.266) or stage IVB (P=0.183)] and Child-Pugh classification [Child-Pugh A (P=0.915) or Child-Pugh B (P=0.676)], there were also no significant differences between the two groups. In conclusion, our study results suggest that TACE could serve as a first-line treatment for stage IV HCC patients as well as sorafenib therapy.

Transcatheter arterial infusion chemotherapy prior to radiofrequency thermal ablation for single hepatocellular carcinoma reduces the risk of intrahepatic distant recurrence.

The aim of the present study was to elucidate the effectiveness of transcatheter arterial infusion chemotherapy (TAI) of the whole liver using an epirubicin-mitomycin-lipiodol emulsion, prior to radiofrequency thermal ablation (RFA), in preventing intrahepatic distant recurrence (IDR) from single hepatocellular carcinoma (HCC). Of the 269 consecutive patients who underwent RFA in our institute for single HCC, a total of 182 patients were analyzed in the present study. The primary endpoint was comparison of the post-RFA IDR-free survival rates in patients treated using TAI with an epirubicin-mitomycin-lipiodol emulsion via the proper hepatic artery (TAI-EML) prior to RFA, and patients that received lipiodol infusion-alone prior to RFA. The secondary endpoints were local tumor progression (LTP) and overall survival (OS). Lipiodol infusion-alone prior to RFA was performed in 88 patients and TAI-EML prior to RFA in 94 patients. The mean tumor size was 2.06 cm (range, 0.9-3.2 cm) in the TAI group and 1.97 cm (range, 0.9-3.3 cm) in the lipiodol-alone group, respectively. The cumulative IDR-free survival rates at 1, 2 and 3 years were 74.0, 50.8 and 34.9%, respectively, in the lipiodol-alone group, and 90.8, 74.8 and 70.0%, respectively, in the TAI group (P<0.001). In terms of the OS, there was a significant difference between these two groups (P=0.048), although there was no significant difference in terms of the LTP (P=0.145). We concluded that TAI-EML prior to RFA appears to be useful in reducing post-RFA IDR and may contribute to improved survival rates.

Branched-chain amino acid treatment before transcatheter arterial chemoembolization for hepatocellular carcinoma.

AIM: To examine the significance of branched-chain amino acid (BCAA) treatment before transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). METHODS: This study included 99 patients who underwent TACE therapy for HCC at our hospital and were followed up without treatment for at least 6 mo between January 2004 and January 2010. They were divided into 2 groups: those receiving BCAA granules (n = 40) or regular diet (n = 59, control). Data obtained were retrospectively analyzed (prior to TACE, and 1 wk, 1, 3, and 6 mo after TACE) in terms of nutritional condition and clinical laboratory parameters (serum albumin level and Child-Pugh score), both of which are determinants of hepatic functional reserve. RESULTS: The BCAA group comprised 27 males and 13 females with a mean age of 69.9 ± 8.8 years. The patients of the BCAA group were classified as follows: Child-Pugh A/B/C in 22/15/3 patients, and Stage II/III/IVA HCC in 12/23/5 patients, respectively. The control group comprised 32 males and 27 females with a mean age of 73.2 ± 10.1 years. In the control group, 9 patients had chronic hepatitis, Child-Pugh A/B/C in 39/10/1 patients, and StageI/II/III/IVA HCC in 1/11/35/12 patients, respectively. Overall, both serum albumin level and Child-Pugh score improved significantly in the BCAA group as compared with the control 3 and 6 mo after TACE (P < 0.05). Further analysis was performed by the following categorization: (1) child-Pugh classification; (2) liver cirrhosis subgroup with a serum albumin level > 3.5 g/dL; and (3) epirubicin dose. A similar trend indicating a significant improvement of all variables in the BCAA group was noted (P < 0.05). CONCLUSION: Treatment with BCAA granules in patients who have undergone TACE for HCC is considered useful to maintain their hepatic functional reserve.

Decrease in alpha-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study.

BACKGROUND: Increasing evidence suggests the efficacy of interferon therapy for hepatitis C in reducing the risk of hepatocellular carcinoma (HCC). The aim of this study was to identify predictive markers for the risk of HCC incidence in chronic hepatitis C patients receiving interferon therapy. METHODS: A total of 382 patients were treated with standard interferon or pegylated interferon in combination with ribavirin for chronic hepatitis C in a single center and evaluated for variables predictive of HCC incidence. RESULTS: Incidence rates of HCC after interferon therapy were 6.6% at 5 years and 13.4% at 8 years. Non-sustained virological response (non-SVR) to antiviral therapy was an independent predictor for incidence of HCC in the total study population. Among 197 non-SVR patients, independent predictive factors were an average alpha-fetoprotein (AFP) integration value ≥10 ng/mL and male gender. Even in patients whose AFP levels before interferon therapy were ≥10 ng/mL, reduction of average AFP integration value to <10 ng/mL by treatment was strongly associated with a reduced incidence of HCC. This was significant compared to patients with average AFP integration values of ≥10 ng/mL (P = 0.009). CONCLUSIONS: Achieving sustained virological response (SVR) by interferon therapy reduces the incidence of HCC in hepatitis C patients treated with interferon. Among non-SVR patients, a decrease in the AFP integration value by interferon therapy closely correlates with reduced risk of HCC incidence after treatment.

Comparison of percutaneous radiofrequency thermal ablation and surgical resection for small hepatocellular carcinoma.

BACKGROUND: The purpose of this investigation was to compare the outcome of percutaneous radiofrequency thermal ablation therapy (PRFA) with surgical resection (SR) in the treatment of single and small hepatocellular carcinoma (HCC). METHODS: We conducted a retrospective cohort study on 231 treatment naive patients with a single HCC ≤ 3 cm who had received either curative PRFA (162 patients) or curative SR (69 patients). All patients were regularly followed up after treatment at our department with blood and radiologic tests. RESULTS: The 1-, 3- and 5-year overall survival rates after PRFA and SR were 95.4%, 79.6% and 63.1%, respectively in the PRFA group and 100%, 81.4% and 74.6%, respectively in the SR group. The corresponding recurrence free survival rates at 1, 3 and 5 years after PRFA and SR were 82.0%, 38.3% and 18.0%, respectively in the PRFA group and 86.0%, 47.2% and 26.0%, respectively in the SR group. In terms of overall survival and recurrence free survival, there were no significant differences between these two groups. In comparison of PRFA group patients with liver cirrhosis (LC) (n = 127) and SR group patients with LC (n = 50) and in comparison of PRFA group patients without LC (n = 35) and SR group patients without LC (n = 19), there were also no significant differences between two groups in terms of overall survival and recurrence free survival. In the multivariate analysis of the risk factors contributing to overall survival, serum albumin level was the sole significant factor. In the multivariate analysis of the risk factors contributing to recurrence free survival, presence of LC was the sole significant factor. The rate of serious adverse events in the SR group was significantly higher than that in the PRFA group (P = 0.023). Hospitalization length in the SR group was significantly longer than in the PRFA group (P = 0.013). CONCLUSIONS: PRFA is as effective as SR in the treatment of single and small HCC, and is less invasive than SR. Therefore, PRFA could be a first choice for the treatment of single and small HCC.

Complete response of advanced hepatocellular carcinoma with multiple lung metastases treated with sorafenib: a case report.

Sorafenib, an oral multikinase inhibitor, has demonstrated clinical efficacy in patients with advanced hepatocellular carcinoma (HCC). However, in the SHARP trial (Sorafenib HCC Assessment Randomized Protocol trial) and the Asia-Pacific trial (conducted in the Asia-Pacific region), no cases of complete response (CR) were reported. Thereafter, only a relatively small number of CR cases were reported worldwide for sorafenib therapy. We herein report a case of CR in a patient treated with sorafenib for 4 months. The patient had advanced HCC with multiple lung metastases, and there has been no recurrence after 8 months following cessation of administration. To our knowledge, this is the first time a female treated with sorafenib alone for HCC has had a CR.