Cost-effectiveness of self-expandable metallic stents as bridge to surgery for obstructive colorectal cancer.

AIM: Self-expandable metallic stent (SEMS) placement is an emergent decompression approach for patients with obstructive colorectal cancer, alongside drainage tube (DT) and emergency surgery (ES). Few reports have compared the health care cost of each treatment. We aimed to compare the efficacy of SEMS as a bridge to surgery (BTS), including health care costs during decompression and colorectal resection, with those of DT and ES. METHODS: This retrospective study enrolled patients treated for acute obstructed colorectal cancer at a single institution from January 2007 to December 2019. A total of 45 patients that underwent placement of a DT, emergency colostomy, or SEMS insertion followed by elective radical colectomy or rectectomy for obstructed colorectal cancer were included, and their data were analyzed. RESULTS: Among 45 patients with obstructive colorectal cancer, 29 (55.6%) patients underwent SEMS, 7 (15.6%) underwent DT, and 9 (20.0%) underwent ES as BTS. The time to oral intake from the decompression treatment in the SEMS group was significantly shorter than that of the DT and ES group (1 vs. 13 vs. 3 day, p < 0.001). Total hospitalization during the decompression and colorectal resection in the SEMS group was significantly shorter that in the DT and ES groups (23 vs. 34 vs. 44 day, p < 0.001). The total health care cost for the decompression and the colorectal resection of DT and SEMS treatment was significantly less inexpensive than ES treatment (180.8 vs. 206.7 vs. 250.3 × 104 yen, p = 0.030). CONCLUSIONS: SEMS insertion as a BTS might represent a cost-effective and safe approach compared to other treatments.

Impact of surgical treatment after sorafenib therapy for advanced hepatocellular carcinoma.

BACKGROUND: For advanced hepatocellular carcinoma (HCC), surgical treatment after sorafenib induction has rarely been reported. We examined the survival benefit of additional surgical treatment in sorafenib-treated patients. METHODS: Thirty-two advanced HCC patients were given sorafenib from July 2009 to July 2012, and we statistically analyzed the relevant predictive factors of the long-term survival. The institutional review board of Kumamoto University Hospital approved this study (Approval number 1038). RESULTS: The median duration of sorafenib administration was 56.5 days (range 5-945). The cumulative overall survival rate was 44.6, 33.4, 26.0 and 17.8% at 1, 2, 3 and 5 years, respectively. The median survival time was 11.2 months. A survival of more than 3 years after the initiation of sorafenib induction was observed in seven patients, five of whom were subjected to additional surgical intervention. Additional surgery was the most significant factor predicting a survival exceeding 3 years (P < 0.0001) and represents an independent prognostic factor [hazard ratio (HR) 0.07; P = 0.01], followed by the total dose of sorafenib. The surgical interventions comprised two hepatic resections ± radiofrequency ablation, two radiofrequency ablations and one lung resection. CONCLUSIONS: A long-term survival might be obtained for select HCC patients given adequate additional surgical treatment, even after sorafenib induction.

Thrombospondin-1 expression may be implicated in liver atrophic mechanism due to obstructed portal venous flow.

AIM: Liver is an amazing organ that can undergo regenerative and atrophic changes inversely, depending on blood flow conditions. Although the regenerative mechanism has been extensively studied, the atrophic mechanism remains to be elucidated. METHODS AND RESULTS: To assess the molecular mechanism of liver atrophy due to reduced portal blood flow, we analyzed the gene expressions between atrophic and hypertrophic livers induced by portal vein embolization in three human liver tissues using microarray analyses. Thrombospondin (TSP)-1 is an extracellular protein and a negative regulator of liver regeneration through its activation of the transforming growth factor-ß/Smad signaling pathway. TSP-1 was extracted as the most upregulated gene in atrophic liver compared to hypertrophic liver due to portal flow obstruction in human. Liver atrophic and hypertrophic changes were confirmed by HE and proliferating cell nuclear antigen staining and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling. In an in vivo model with portal ligation, TSP-1 and phosphorylated Smad2 expression were continuously induced at 6 h and thereafter in the portal ligated liver, whereas the induction was transient at 6 h in the portal non-ligated liver. Indeed, while cell proliferation represented by proliferating cell nuclear antigen expression at 48 h was induced in the portal ligated liver, the sinusoidal dilatation and hepatocyte cell death with terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling was detectable at 48 h in the portal ligated liver. CONCLUSIONS: Obstructed portal flow induces persistent TSP-1 expression and transforming growth factor-ß/Smad signal activation in atrophic liver. Thrombospondin-1 may be implicated in the liver atrophic change due to obstructed portal flow as a pro-atrophic factor.

LINE-1 methylation level and prognosis in pancreas cancer: pyrosequencing technology and literature review.

PURPOSE: Global DNA hypomethylation plays an important role in genomic instability and carcinogenesis. The long interspersed nucleotide element-1 (LINE-1) methylation level is a good surrogate marker of the global DNA methylation level. Previously, we demonstrated a strong relationship between LINE-1 hypomethylation and poor prognosis in certain cancers. However, the relationship between the LINE-1 methylation level and the clinical outcome of pancreatic cancer (PC) remains unclear. METHODS: We used a pyrosequencing assay to measure LINE-1 methylation levels in 126 samples of resected PC and evaluated the prognostic value of the LINE-1 methylation level. RESULTS: LINE-1 methylation levels were significantly lower in PC tissues than in matched noncancerous pancreatic tissues (p = 0.039, n = 36). The tumoral LINE-1 methylation range was 41.3-92.8 (n = 126, mean 77.7, median 78.5, standard deviation 5.7). The LINE-1 methylation level was unrelated to clinical and pathological features. Moreover, LINE-1 hypomethylation was not significantly associated with overall survival, cancer specific survival, or disease-free survival (log-rank p = 0.30, p = 0.18 and p = 0.50, respectively). CONCLUSION: The LINE-1 methylation level appears not to be associated with poor prognosis in PC. The effect of the LINE-1 methylation level on the survival of PC patients needs to be confirmed in a larger-cohort study.

Prognostic Impact of Visceral Fat Amount and Branched-Chain Amino Acids (BCAA) in Hepatocellular Carcinoma.

BACKGROUND: Dysregulation of lipid and amino acid metabolism in patients with liver diseases results in obesity-related carcinogenesis and decreased levels of branched-chain amino acids (BCAA), respectively. This study assessed the clinical and prognostic impact of visceral fat amount (VFA) and its association with amino acid metabolism in patients with hepatocellular carcinoma (HCC). METHODS: In this study, 215 patients who underwent hepatic resection for HCC were divided into two groups based on VFA criteria for metabolic abnormalities in Japan. Computed tomography was used to measure VFA at the third lumbar vertebra in the inferior direction. RESULTS: Of the 215 patients, 132 had high and 83 had low VFA. High VFA was significantly associated with older age and higher body mass index (BMI), subcutaneous fat amount, and BCAA, but not with liver function, nutrient status, or tumoral factors. VFA was positively correlated with BMI (P < 0.0001; r = 0.63) and BCAA levels (P < 0.0001; r = 0.29). Overall survival was significantly greater in the high than in the low VFA group (P = 0.002). Multivariate analyses showed that high VFA [hazard ratio (HR) 7.06; P = 0.024] and neutrophil/lymphocyte ratio (HR 3.47; P = 0.049) were significantly prognostic of overall survival, whereas subcutaneous fat amount, BMI, BCAA, serum albumin, and prognostic nutritional index were not. CONCLUSIONS: High VFA was associated with a high BCAA level, with high VFA prognostic of improved overall survival in Japanese patients with HCC.

[Short-term adjuvant hepatic arterial infusion chemotherapy after hepatic resection for hepatocellular carcinoma with macrovascular invasion].

BACKGROUND: Prognosis of patients with hepatocellular carcinoma (HCC) with macrovascular invasion is extremely poor even after hepatic resection. Herein, the efficacy of short-term adjuvant hepatic arterial infusion chemotherapy (HAI) for HCC with macrovascular invasion has been studied. PATIENTS AND METHODS: From 1997 to 2013, 39 patients with HCC (BVp3, Vv3, or B3) undergoing hepatic resection were enrolled(group A: adjuvant HAI, n=21, group B: hepatectomy alone, n=18). RESULTS: Clinical and demographic characteristics were similar in the 2 groups. Five-year disease-free survival (DFS) rates were 31.0% and 6.2% in group A and group B, respectively (p=0.008). In multivariate analysis for DFS, adjuvant HAI was the only independent prognostic factor (hazard ratio: 0.44, p=0.04). In group A, the intrahepatic recurrence rate was significantly lower (33% vs 72%, p=0.01) compared to group B, but rates of extrahepatic recurrence were similar in the 2 groups (19% vs 22%). The rate of overall survival was marginally higher in group A compared to group B (51% vs 19%, respectively, p= 0.06). CONCLUSION: Short-term adjuvant HAI after hepatic resection may significantly improve DFS for HCC patients with macrovascular invasion.

Frailty Predicts Severe Postoperative Complication after Elective Hepatic Resection.

BACKGROUND: Frail patients are likely to suffer from postoperative complication, but this assumption has not been well confirmed. OBJECTIVES: This study aims to clarify the importance of frailty in patients undergoing hepatectomy for predicting severe postoperative complications. METHOD: One hundred and forty-three patients aged >65 years undergoing hepatectomy between 2011 and 2016 were enrolled in this study. The relevance of frailty versus sarcopenia for postoperative outcome was assessed. We defined clinical frailty (CF) as a CF scale >4. Sarcopenia was defined by the total muscle area at the level of the third lumbar vertebra measured on computed tomography. RESULTS: There were 16 patients (11%) with CF and 80 patients (56%) with sarcopenia. CF was associated with high age (p < 0.0001), severe postoperative complications (Clavien-Dindo classification ≥3) (p = 0.0059), and postoperative in-hospital stay (p = 0.0013). On the other hand, sarcopenia was not associated with postoperative outcome. Logistic regression analysis revealed that only CF was an independent predictor of severe postoperative complication (risk ratio of 4.2; p = 0.017). The occurrence of organ/space surgical site infection was significantly higher in the frailty group than in the non-frailty group. CONCLUSION: CF, but not sarcopenia, is a robust predictor of severe postoperative complications for patients undergoing hepatectomy.

Evaluation of patients with hepatic portal venous gas who can be treated with conservative therapy.

Aim: Hepatic portal venous gas is an indication for emergency surgery and reportedly has a high mortality rate. However, these days, cases of hepatic portal venous gas associated with milder disease are increasing. In this report, we compared two groups to investigate whether there were any objective indicators for selecting conservative therapy. Methods: From July 2007 to August 2011, 19 patients with hepatic portal venous gas were evaluated at our hospital. The condition was diagnosed by computed tomography imaging. Vital signs, laboratory test results, and physical examination findings were compared. Results: The A group included 12 patients who could be treated with conservative therapy. The B group included 7 patients who could not be treated with conservative therapy. The combined mortality rate was 31.5% (6/19 patients). There was a significant difference in the pulse rate and shock index. In the A group, none of the patients had signs of peritoneal irritation. However, in the B group, physical examination revealed signs of peritoneal irritation in all patients. Conclusion: Conservative therapy may be possible in patients with hepatic portal venous gas, depending on the cause. Evaluation of vital signs and serial changes on physical examination are important.

Intra-aortic balloon pump-assisted major hepatectomy in a case with coronary disease.

Clinically, we often encounter cancer patients who also have cardiovascular disease such as coronary artery disease. We experienced a case of severe coronary artery disease and a large hepatocellular carcinoma in a 69-year-old man. To reduce the risk of a perioperative cardiovascular event during mesohepatectomy, an elective intra-aortic balloon pump (IABP) was used. After an uneventful recovery, the patient was discharged on day 15. While IABP is frequently introduced in cardiac surgery, there have been few reports of its use during liver surgery. Here, we present IABP-assisted major hepatectomy as an option in a patient with both cancer and coronary artery disease.

Liver abscess caused by multidrug-resistant Pseudomonas aeruginosa treated with colistin; a case report and review of the literature.

A 77-year-old man had undergone left-lobe liver resection and a choledochojejunostomy six years previously, and thereafter he suffered from a postoperative relapse of cholangitis. He was admitted to our hospital due to liver abscesses and bacteremia caused by multidrug-resistant Pseudomonas aeruginosa. Empirical treatment with piperacillin/tazobactam was started, and the patient initially recovered. However, he developed a second case of sepsis caused by piperacillin/tazobactam-resistant P. aeruginosa bacteremia originating from a new liver abscess. We changed the piperacillin/tazobactam to colistin and flomoxef and continued the two antibiotics for one month. During the antibiotic therapy, the patient successfully underwent bile duct stent placement.