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.

Comparison of five staging systems in hepatocellular carcinoma treated with sorafenib: A single-center experience.

To the best of our knowledge, none of the prognostic staging systems for hepatocellular carcinoma (HCC) patients who underwent sorafenib therapy is universally adopted or preferred. In the present study, we aimed to compare prognostic ability among five prognostic systems, including the Japan Integrated Staging (JIS) system, the Barcelona Clinic Liver Cancer classification system, the tumor-node-metastasis classification system, the Cancer of the Liver Italian Program scoring system and the Chinese University Prognostic Index (CUPI) scoring system for HCC patients who received sorafenib therapy. A total of 143 HCC patients treated with sorafenib were analysed. We compared prognostic ability among the five prognostic systems using the likelihood ratio (LR) χ2 test, linear trend χ2 test and concordance index (c-index). Our cohort included 114 men and 29 women. The median patient age was 71 years (range, 45-89 years). A total of 102 patients were classified as Child-Pugh A and 41 as Child-Pugh B, whereas 31 patients (21.7%) had portal vein invasion and 63 (44.1%) extrahepatic metastases. The median survival time was 6.9 months. In the LR χ2 test, the CUPI scoring system had the highest value (35.804), followed by the JIS system (17.469). In the linear trend χ2 test, the CUPI scoring system had the highest value (17.523), followed by the JIS system (15.819). In addition, the JIS system had the highest value in the 6-month c-index (0.659) as well as in the 1-year c-index (0.674). However, the CUPI classification system had the lowest value in the 1-year c-index (0.590). In conclusion, the JIS system may be an appropriate staging system for HCC patients undergoing sorafenib therapy.

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.

Proposal of the performance status combined Japan Integrated Staging system in hepatocellular carcinoma complicated with cirrhosis.

The present study examined the prognostic ability of our proposed performance status combined Japan Integrated Staging (PS-JIS) system in hepatocellular carcinoma (HCC) patients with liver cirrhosis (LC) comparing with other four prognostic systems including original JIS system, the Barcelona Clinic Liver Cancer classification system, TNM classification system and the Cancer of the Liver Italian Program (CLIP) scoring system. A total of 1,170 HCC patients complicated with LC were analysed. The disease was staged for all analysed patients by means of the five staging systems. The cumulative overall survival (OS) rate was calculated by Kaplan-Meier method and tested by log-rank test. We also examined prognostic factors associated with OS using univariate and multivariate analyses and compared the prognostic ability in each prognostic system using concordance index (c-index) at 1-, 3- and 5-year time-points. Overall significance in each prognostic system was P<0.001. In the multivariate analyses, tumor number, Child-Pugh classification, PS, initial treatment modality and several laboratory parameters were significant independent predictors linked to OS. For all cases, in each time-point, the c-index of PS-JIS system was the highest among five staging systems (0.847, 0.816 and 0.808, respectively), indicating that PS-JIS system has the best predictability among these staging systems. According to subgroup analyses stratified by initial treatment modality, in patients treated with surgical resection (n=205), CLIP scoring system had the highest c-index at every time-point, whereas in patients treated with percutaneous ablative therapies (n=632) at 3- and 5-year time-point and in those with transcatheter arterial therapies (n=281) at every time-point, the c-index of PS-JIS system was the highest. In conclusion, the proposed PS-JIS score can be a useful prognostic system for HCC patients complicated with liver cirrhosis.

Hyponatremia in hepatocellular carcinoma complicating with cirrhosis.

BACKGROUND AND AIMS: We aimed to investigate the effect of serum sodium level on survival in hepatocellular carcinoma (HCC) patients complicating with liver cirrhosis (LC). METHODS: A total of 1170 HCC patients with LC were analysed. We classified these patients into three groups according to serum sodium level at HCC diagnosis: group A (n=96); serum sodium ≤135 mmol/L, group B (n=520); 135 mmol/L < serum sodium ≤140 mmol/L, group C (n=554); serum sodium >140 mmol/L. We compared the baseline characteristics and overall survival (OS) among these three groups. Furthermore, we examined the factors linked to OS using univariate and multivariate analyses. RESULTS: In our results, decreased baseline serum sodium level was significantly associated with Child-Pugh classification and HCC stage along with several laboratory parameters in groups A, B and C. The median follow-up period was 1.1 years in group A, 2.4 years in group B and 3.3 years in group C. The 1-, 3- and 5-year cumulative OS rates in groups A, B and C were 64.8%, 46.9% and 25.7%, respectively, in group A, 85.5%, 60.5% and 41.1%, respectively, in group B and 90.7%, 66.6% and 48.2%, respectively, in group C (P<0.001). The multivariate analyses showed that Child-Pugh classification (P<0.001), HCC stage (P<0.001), serum sodium (P<0.001), aspartate aminotransferase ≥57 IU/L (P=0.002), alkaline phosphatase ≥348 IU/L (P<0.001), alpha-fetoprotein ≥29.2 ng/mL (P=0.019) and des-γ-carboxy prothrombin ≥55 mAU/mL (P<0.001) were significant independent predictors linked to OS. CONCLUSION: Lower serum sodium concentration is a useful predictor in HCC patients complicating with LC.

Clinical implication of performance status in patients with hepatocellular carcinoma complicating with cirrhosis.

BACKGROUND AND AIMS: The aims of our study were to elucidate the relationship between baseline characteristics of hepatocellular carcinoma (HCC) patients complicating with liver cirrhosis (LC) and performance status (PS) and to investigate the impact of PS on survival in patients with HCC complicating with LC. METHODS: In a total of 1003 patients diagnosed with HCC complicating with LC, we divided into two groups of PS ≥1 (n=251) and PS 0 (n=752) as evaluated by using the Eastern Cooperative Oncology Group criteria at the time of HCC diagnosis. Baseline characteristics between these two groups were compared. We also performed univariate and multivariate analyses of factors contributing to overall survival (OS). RESULTS: The median follow-up period was 1.6 years in the PS ≥1 group and 3.1 years in the PS 0 group. The 1-, 3- and 5-year OS rates after each initial therapy for HCC were 90.3%, 67.4% and 49.8%, respectively, in the PS 0 group and 73.4%, 42.0% and 17.7%, respectively, in the PS ≥1 group (P<0.001). A worse PS was significantly associated with age, gender, Child-Pugh classification, HCC stage, Japan Integrated Staging score, initial treatment option for HCC, maximum tumor size, alanine aminotransferase value, hypoalbuminemia, hyperbilirubinemia, renal insufficiency, hyponatremia, prothrombin time prolongation, platelet count and tumor marker level. In multivariate analyses, poorer PS was an independent predictor linked to OS with a hazard ratio of 1.773 (P<0.001). CONCLUSIONS: PS was closely associated with status of HCC patients with LC and could be an important predictor for these populations.

Transcatheter arterial chemoembolization for intermediate-stage hepatocellular carcinoma: clinical outcome and safety in elderly patients.

AIM: The aim of our study was to compare clinical outcomes between elderly patients aged ≥75 years (elderly group, n=66) with intermediate hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE) and younger patients aged <75 years (control group, n=84) with intermediate HCC undergoing TACE. METHODS: Clinical outcomes, including overall survival (OS) and tumor response rate at initial therapy, were compared between these two groups. RESULTS: The median survival time and the 1- and 3-year cumulative OS rates were 2.90 years and 84.1% and 48.0%, respectively, in the elderly group and 2.44 years and 78.2% and 39.3%, respectively, in the control group (p=0.887). The objective response rate in the elderly group was 81.8% (54/66 patients), while that in the control group was 78.6% (66/84 patients) (p=0.227). CONCLUSION: Elderly patients with intermediate HCC undergoing TACE had a prognosis comparable with that of younger patients with intermediate HCC undergoing TACE.

Clinical efficacy of non-transplant therapies in patients with hepatocellular carcinoma with Child-Pugh C liver cirrhosis.

AIM: To compare clinical outcome in patients with Child-Pugh C hepatocellular carcinoma (HCC) treated with non-transplant therapies and those treated with best supportive care. PATIENTS AND METHODS: A total of 182 patients with HCC with Child-Pugh C cirrhosis were analyzed. Patients were classified into two groups: patients treated with non-transplant therapies (n=113, treated group) and untreated patients (n=69, untreated group). Furthermore, for reducing the bias in patient selection, a propensity score matching analysis was performed (55 pairs). RESULTS: The median survival time in the treated group was significantly longer than that in the untreated group (1.16 years vs. 0.21 years, p<0.001). After propensity score matching, the median survival time in the treated group remained significantly longer than that in the untreated group (0.95 years vs. 0.17 years, p=0.01). CONCLUSION: In patients with HCC with Child-Pugh C cirrhosis, those treated with non-transplant therapies might have longer survival than untreated patients.

Clinical significance of early interventional therapy of branched-chain amino acid granules in patients with hepatocellular carcinoma: propensity score matching analysis.

We examined whether supplementation of branched-chain amino acid (BCAA) granules in an early stage of underlying liver disease (pretreatment serum albumin levels ≥ 3.6 g/dl) can improve overall survival (OS) after therapy for hepatocellular carcinoma (HCC) using propensity score matching analysis. We compared OS between patients treated with BCAA granules and control group patients in two propensity score matched cohorts (cohort 1: pretreatment serum albumin levels ≥ 3.6 g/dl and <4.0 g/dl, 111 pairs; cohort 2: pretreatment serum albumin levels ≥ 4.0 g/dl, 61 pairs). We also performed subgroup analyses according to HCC stage. In cohort 1 patients, the OS rate in the BCAA group (median follow-up period, 2.9 years) tended to be higher compared to that in the control group (median follow-up period, 2.6 years) (1- and 3-year OS rates; 97.2 and 75.5% in the BCAA group and 87.2 and 64.5% in the control group, P=0.072), whereas in cohort 2 patients, the difference in the two groups did not reach significance in terms of OS [1- and 3-year OS rates; 83.2 and 60.7% in the BCAA group (median follow-up period, 2.3 years) and 91.8 and 66.0% in the control group (median follow-up period, 2.9 years), P=0.871]. In subgroup analyses, in cohort 1, in patients with HCC stage III or IV, the OS rate in the BCAA group (n=37) was significantly higher compared to that in the control group (n=34) (P=0.017). In other subgroup analyses, no significant difference in the two groups was found in terms of OS. In conclusion, early interventional therapies using BCAA granules may be effective in some selected HCC patients.

Effect of treatment with branched-chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma.

AIM: To examine the effect of branched-chain amino acid (BCAA) therapy for patients with unresectable hepatocellular carcinoma (HCC) treated with sorafenib. METHODS: Seventy-eight subjects with unresectable HCC with a serum level of albumin of 3.5 g/dL or less treated with sorafenib were evaluated. They were classified into two groups: those receiving BCAA granules (n = 34; BCAA group) or a regular diet (n = 44; control group). We compared overall survival and administration period of sorafenib, and analyzed absolute changes in serum levels of albumin during sorafenib therapy in 41 patients who continued sorafenib therapy for 1 month or more with a follow up of more than 3 months. RESULTS: Median survival time (MST) in BCAA and control groups was 350 and 143 days (P = 0.007), respectively. Median administration period of sorafenib in the two groups was 59 and 41 days (P = 0.018). In the 41 patients described above, at 1 month, there was no significant change in the serum level of albumin between the two groups, but at 3 months, the difference in the absolute change in the serum level of albumin in the two groups reached significance (P = 0.023). In these subgroup analyses, the administration period of sorafenib as well as the MST in the BCAA group were significantly longer than those in the control group (P = 0.020 and = 0.004). CONCLUSION: BCAA treatment during sorafenib therapy in HCC patients is useful for maintaining hepatic functional reserve, which may help to avoid early discontinuance of sorafenib therapy and improve survival.

Comparison of transcatheter arterial chemoembolization and transcatheter arterial chemotherapy infusion for patients with intermediate-stage hepatocellular carcinoma.

The aim of the present study was to compare clinical outcomes in patients with intermediate-stage hepatocellular carcinoma (HCC) who underwent the following treatments: transcatheter arterial chemoembolization (TACE) using an epirubicin-mitomycin-lipiodol (EML) emulsion at initial therapy (TACE group; n=145), and transcatheter chemotherapy infusion (TACI) using an EML emulsion at initial therapy (TACI group; n=81). Overall survival (OS) and treatment efficacy in the TACE and TACI groups were retrospectively compared. Prognostic factors associated with OS were examined using univariate and multivariate analyses. Treatment-related mortality was also calculated. The median observation periods were 1.8 years (range, 0.2-9.0 years) in the TACE group and 2.0 years (range, 0.2-8.7 years) in the TACI group. The median survival time and the 1-, 2-, 3- and 5-year cumulative OS rates were 2.68 years and 81.5, 63.4, 43.9 and 32.7%, respectively, in the TACE group, and 2.64 years and 85.0, 60.0, 43.2 and 26.0%, respectively, in the TACI group (P=0.691). The objective response rate was significantly higher in the TACE group compared to the TACI group (80.0 vs. 66.7%; P=0.009). Using multivariate analysis, the Child-Pugh classification (P=0.017), tumor number ≤5 (P=0.045) and des-γ-carboxy prothrombin level >100 mAU/ml (P=0.002) were found to be significant predictors linked to OS. In all subgroup analyses involving Child-Pugh classification, maximum tumor size and tumor distribution, the differences in the two groups did not reach statistical significance in terms of OS. Treatment mortality was 0% in the two groups. In conclusion, patients with intermediate-stage HCC had a comparable prognosis when treated with TACI or TACE.

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.

Percutaneous radiofrequency ablation therapy for recurrent hepatocellular carcinoma.

AIM: To compare the overall survival (OS) in patients without recurrent hepatocellular carcinoma (HCC) after initial radiofrequency ablation (RFA) and in those with recurrence, treated with repeat-RFA. PATIENTS AND METHODS: We compared OS between patients without recurrence (group A; n=150) and those with recurrence treated with repeat-RFA (group B; n=130). RESULTS: One-, 3- and 5-year OS after initial RFA was 92.6%, 84.1% and 81.0%, respectively, in group A, and 99.0%, 84.1% and 61.8% in group B (p=0.296). There was no significant difference in OS between group A patients and patients with a single recurrent HCC (p=0.834). On multivariate analysis, serum albumin >3.5 g/dl and first HCC recurrence, comprising of two or three nodules were significant predicting factors of poorer OS. CONCLUSION: Even if HCC recurs after initial RFA, survival comparable to that of patients without recurrence can be achieved in patients with a single recurrent tumor treated with repeat-RFA.

A case of HIV-associated lymphoproliferative disease that was successfully treated with highly active antiretroviral therapy.

We report a case of a 41-year-old male with human immunodeficiency virus (HIV)-associated lymphoproliferative disease (LPD) who was successfully treated with highly active antiretroviral therapy (HAART). He presented with epigastralgia, and an upper endoscopic examination revealed submucosal tumors and ulcerations in his stomach. Histopathologic examination of a biopsy specimen resulted in a diagnosis of diffuse large B-cell lymphoma. He also showed systemic lymphadenopathy; whereas, a concurrent inguinal lymph node biopsy produced a diagnosis of follicular hyperplasia. He was treated with CHOP chemotherapy but the response was poor. He demonstrated several immunological abnormalities, such as eosinophilia and bone marrow insufficiency, and was suspected to be in an immunocompromised state. He was examined for HIV infection and turned out to be positive. The gastric and inguinal lymph node specimens were re-evaluated and diagnoses of HIV-LPD and HIV lymphadenitis were made, respectively. He was treated with HAART and achieved complete remission and has remained tumor-free for 20 months. To the best of our knowledge, there is no previous report in which HIV-LPD was successfully treated with antiretroviral therapy alone. It is assumed that HAART resulted in the restoration of anti-tumor immunity in this case, which led to the eradication of LPD cells.

Simultaneous occurrence of inflammatory bowel disease and myelodysplastic syndrome due to chromosomal abnormalities in bone marrow cells.

BACKGROUND/AIMS: Although chromosomal abnormalities in bone marrow (BM) cells, such as trisomy 8, are risk factors for the development of inflammatory bowel diseases (IBD) as well as myelodysplastic syndrome (MDS), the mechanisms of how these cytogenetic abnormalities cause intestinal inflammation are poorly understood. METHODS AND RESULTS: A 55-year-old man with a 3-month history of watery diarrhea, fever and abdominal pain was admitted. Blood examinations revealed pancytopenia. Pathological analysis and endoscopic images of the entire colon led to the diagnosis of IBD of unclassified type. BM examination showed that the pancytopenia was due to MDS and that his BM cells had dual chromosomal abnormalities: 47, XY, +1, der(1;7)(q10;p10), +8. Immunological studies using peripheral blood monocytes from this patient revealed that the dual chromosomal abnormalities of BM cells led to the development of colitogenic monocytes producing a large amount of pro-inflammatory cytokines and showing resistance to apoptosis upon stimulation with microbial antigens. CONCLUSION: An abnormal karyotype of BM cells is not only responsible for the development of MDS, but also for IBD in this case.