Endoscopic treatment of Bouveret syndrome with a combination of electrohydraulic lithotripsy and balloon expansion: A case report.

Bouveret syndrome is a rare type of ileus caused by the impaction of gallstones passing through a cholecystoenteric fistula in the duodenum. Endoscopic treatment with minimally invasive procedures is preferable for patients with this syndrome, typically for elderly individuals with a high surgical risk. Conventional endoscopic techniques often fail to remove impacted stones that are generally large and occasionally solid. We report the case of an 88-year-old bedridden woman with severe dementia who presented with difficulty in breathing. The patient was diagnosed with aspiration pneumonia. In addition, computed tomography showed a cholecystoduodenal fistula and a gallstone 37 mm in diameter that impacted the duodenal bulb. Bouveret syndrome was diagnosed on the basis of the computed tomography findings. The impacted stone was too large and hard to split with standard endoscopic lithotripsy using grasping forceps, mechanical lithotripter, polypectomy snare, basket catheter, and electrohydraulic lithotripsy (EHL). However, EHL with a dual-channel therapeutic endoscope was achieved to drill a narrow hole approximately 20 mm deep into the stone, in four sessions. The stone was subsequently split by inflating the balloon, which was inserted into the hole, to 10 mm in diameter at 3 atm. All the split stones were spontaneously excreted during defecation after a few days. If the gallstone is too hard to fragment by endoscopic EHL alone, a combination of EHL and balloon expansion might be a useful alternative.

Longitudinal increase in albumin-bilirubin score is associated with non-malignancy-related mortality and quality of life in patients with liver cirrhosis.

Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients' prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients' quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin-bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.

Intestinal duplication diagnosed preoperatively with double-balloon enteroscopy: an extremely rare case report and literature review.

Gastrointestinal duplications are congenital malformations that are usually observed in pediatric patients. Diagnosis in adulthood is quite rare, and preoperative diagnosis of gastrointestinal duplication is difficult, particularly in the small intestine. We encountered an extremely rare adult case of duplication of the jejunum, which showed a stomach-like form diagnosed using double-balloon enteroscopy (DBE). The patient was an 18-year-old male who had been experiencing upper abdominal pain and vomiting repeatedly without any triggers for 3 years. Various examinations were performed, but no cause of symptoms was found. DBE revealed a narrow opening of the lumen at the upper jejunum, and the lumen was covered with mucosal folds similar to those of the stomach. Enteroclysis via DBE showed a tubular structure on the mesenteric side of the jejunum. We diagnosed a jejunal tubular duplication with ectopic gastric mucosa and underwent partial small bowel resection. The patient's abdominal symptoms resolved. From this, DBE can be a useful tool for diagnosing intestinal duplication in adults. We believe that this case and literature review will facilitate the accurate and prompt diagnosis of small intestinal duplication.

Long-term survival of 11 years with multidisciplinary therapy for hepatocellular carcinoma metastasis to the ovary and peritoneum: a case report.

We herein report a rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd-Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread.

Rapid decline in visceral adipose tissue over 1 month is associated with poor prognosis in patients with unresectable pancreatic cancer.

BACKGROUND: Involuntary weight loss related to cachexia is common in patients with advanced cancer, but the association between body composition changes and survival is still unclear in pancreatic cancer. METHODS: We retrospectively reviewed the clinical outcomes of 55 patients with advanced pancreatic cancer undergoing palliative therapy or best supportive care (BSC). The skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR) were calculated based on the cross-sectional area on two sets of computed tomography images obtained at cancer diagnosis and 1 month later before treatment. The prognostic value of body composition indexes at diagnosis and the changes in those indexes over 1 month was then evaluated. RESULTS: In total, 45 patients (81.8%) received chemotherapy, chemoradiation, or radiation therapy, whereas the remaining patients underwent BSC. There were 27 patients (49.1%) who had low SMI at cancer diagnosis. Univariate analysis showed no significant associations between the baseline body composition indexes including SMI, VATI, SATI, and VSR and survival. Meanwhile, male sex (HR, 2.79; 95% CI, 1.16-6.71, p = 0.022) and higher decrease in VATI over 1 month (HR, 2.41; 95% CI, 1.13-5.13, p = 0.023) were identified as independent risk factors for mortality in multivariate analysis. CONCLUSION: Rapid decline in VAT over 1 month is closely associated with poorer survival in unresectable advanced pancreatic cancer. A short-term assessment of body composition changes may be a rational approach to predict prognosis in these patients.

Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice.

We describe a novel therapeutic approach for cirrhosis using mesenchymal stem cells (MSCs) and colony-stimulating factor-1-induced bone marrow-derived macrophages (id-BMMs) and analyze the mechanisms underlying fibrosis improvement and regeneration. Mouse MSCs and id-BMMs were cultured from mouse bone marrow and their interactions analyzed in vitro. MSCs, id-BMMs, and a combination therapy using MSCs and id-BMMs were administered to mice with CCl4 -induced cirrhosis. Fibrosis regression, liver regeneration, and liver-migrating host cells were evaluated. Administered cell behavior was also tracked by intravital imaging. In coculture, MSCs induced switching of id-BMMs toward the M2 phenotype with high phagocytic activity. In vivo, the combination therapy reduced liver fibrosis (associated with increased matrix metalloproteinases expression), increased hepatocyte proliferation (associated with increased hepatocyte growth factor, vascular endothelial growth factor, and oncostatin M in the liver), and reduced blood levels of liver enzymes, more effectively than MSCs or id-BMMs monotherapy. Intravital imaging showed that after combination cell administration, a large number of id-BMMs, which phagocytosed hepatocyte debris and were retained in the liver for more than 7 days, along with a few MSCs, the majority of which were trapped in the lung, migrated to the fibrotic area in the liver. Host macrophages and neutrophils infiltrated after combination therapy and contributed to liver fibrosis regression and promoted regeneration along with administered cells. Indirect effector MSCs and direct effector id-BMMs synergistically improved cirrhosis along with host cells in mice. These studies pave the way for new treatments for cirrhosis. Stem Cells Translational Medicine 2019;8:271&284.

Prognostic value of subcutaneous adipose tissue volume in hepatocellular carcinoma treated with transcatheter intra-arterial therapy.

BACKGROUND: Prognosis of patients with hepatocellular carcinoma (HCC) who undergo transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, is affected by many clinical factors including liver function and tumor progression. However, the effect of body composition such as skeletal muscle and visceral and subcutaneous adipose tissues (VAT and SAT, respectively) on the prognosis of these patients remains unclear. We investigated the prognostic value of body composition in HCC patients treated with transcatheter intra-arterial therapies. PATIENTS AND METHODS: This study retrospectively evaluated 100 HCC patients treated with transcatheter intra-arterial therapies between 2005 and 2015. Areas of skeletal muscle, VAT, and SAT were measured on computed tomography images at third lumbar vertebra level and normalized by the height squared to calculate the skeletal muscle index, VAT index, and SAT index (SATI). The visceral to subcutaneous adipose tissue area ratio was also calculated. Overall survival (OS) was compared between high- and low-index groups for each body composition. Furthermore, prognostic significance was assessed by univariate and multivariate analyses using Cox proportional hazards models. RESULTS: Among the body composition indexes, only SATI could significantly differentiate OS (p=0.012). Multivariate analysis showed that SATI (low- vs. high-SATI: HR, 2.065; 95% CI, 1.187-3.593; p=0.010), serum albumin (<3.5 vs. ≥3.5 g/dL; HR, 2.007; 95% CI, 1.037-3.886; p=0.039), serum alpha-fetoprotein (<20 vs. ≥20 ng/mL; HR, 0.311; 95% CI, 0.179-0.540; p<0.001), and Modified Response Evaluation Criteria in Solid Tumors assessment (complete response+partial response+stable disease vs. progressive disease; HR, 0.392; 95% CI, 0.221-0.696; p=0.001) were indicated as independent prognostic factors for OS. CONCLUSION: High SAT volume is associated with better survival outcomes in HCC patients treated with transcatheter intra-arterial therapies. Elucidation of the mechanisms regulating SAT volume may offer a new therapeutic strategy for these patients.

Rapidly declining skeletal muscle mass predicts poor prognosis of hepatocellular carcinoma treated with transcatheter intra-arterial therapies.

BACKGROUND: The impact of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) who receive transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, remains unclear. We investigated the prognostic value of skeletal muscle loss (SML) stratified by cutoffs for sarcopenia and rate of change in skeletal muscle mass over 6 months. METHODS: We retrospectively evaluated 102 patients with HCC treated with transcatheter intra-arterial therapies between 2005 and 2015. Computed tomography images of the third lumbar vertebra (L3) were analyzed to obtain the skeletal muscle area normalized for the height squared, defined as the skeletal muscle index at L3 (L3 SMI), before and 6 months after treatment. Low or high SMI was defined using cutoff values of 42 cm2/m2 in men and 38 cm2/m2 in women. The rate of change in skeletal muscle mass (ΔL3 SMI) over 6 months was calculated. Overall survival (OS) was compared in groups classified by baseline L3 SMI and ΔL3 SMI; prognostic significance was assessed with univariate and multivariate analyses, using Cox proportional hazards models. RESULTS: OS did not differ significantly between groups with low (n = 31) and high (n = 71) SMI at baseline (P = 0.172), but OS was significantly poorer in patients with SML (n = 41), defined as ΔL3 SMI < - 4.6% over 6 months than in those without SML (n = 61, P = 0.018). On multivariate analysis, SML (hazard ratio [HR], 1.675; 95% confidence interval [CI], 1.031-2.721; P = 0.037), serum alpha-fetoprotein ≥20 ng/mL (HR, 2.550; 95% CI, 1.440-4.515; P = 0.001), and maximum tumor diameter ≥ 30 mm (HR, 1.925; 95% CI, 1.166-3.179; P = 0.010) were independent predictors of poor OS. Baseline L3 SMI was not significantly associated with OS (HR, 1.405; 95% CI, 0.861-2.293; P = 0.174). CONCLUSIONS: ΔL3 SMI was an independent prognostic factor in patients with HCC treated with transcatheter intra-arterial therapies. Further study is required to reveal whether prevention of skeletal muscle depletion might be a new therapeutic strategy to contribute to improved clinical outcomes in patients with HCC.

Clinical outcome of hepatocellular carcinoma can be predicted by the expression of hepatic progenitor cell markers and serum tumour markers.

The high heterogeneity of hepatocellular carcinomas (HCCs) complicates stratification of HCC patients for treatment. Therefore, it is necessary to establish a comprehensive panel of HCC biomarkers related to tumour behaviour and cancer prognosis. Resected HCCs from 251 patients were stained for hepatic progenitor cell (HPC) markers epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), delta-like 1 homolog (DLK1), and cytokeratin 19 (CK19). Staining patterns were analysed for their prognostic association with relapse-free survival and overall survival. α-Fetoprotein (AFP), lectin-reactive α-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin (DCP) were assessed as indicators of HPC protein expression. Expression pattern of HPC markers correlated with tumour malignancy indicated by high AFP/AFP-L3 serum levels, more frequent vascular invasion, and poorer tumour differentiation. EpCAM expression, DCP ≥300 mAU/ml, age ≥60, and Child-Pugh score grade B or C were independent prognostic factors of poor outcome and were used in a new scoring system for HCC prognosis after operation. Expression of two or more HPC markers was a significant predictor of poor HCC outcome and serum levels of AFP/AFP-L3 correlated with the expression of HPC proteins. Our study paved the way for further elucidation of the association among HPC markers, serum tumour markers, and HCC clinical outcome for precision medicine.

Effective prevention of sorafenib-induced hand-foot syndrome by dried-bonito broth.

BACKGROUND: Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand-foot syndrome (HFS) is the most common, occurring in 30%-50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. MATERIALS AND METHODS: To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. RESULTS: A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow (p = 0.009) and significantly decreased occurrence of HFS (p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period (p = 0.035). CONCLUSION: The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow.

Bleeding from a Small-Intestinal Ulcer Associated with Chronic Hepatitis C.

BACKGROUND Hepatitis C virus infection is probably the most common chronic viral infection and affects an estimated 180 million people worldwide. Extrahepatic manifestations are well recognized among patients with chronic HCV infection. CASE REPORT We report a case of melena occurring in a 69-year-old Japanese man who had been diagnosed with CHC and who was treated with antiviral therapy. CONCLUSIONS Finally, he was diagnosed with multiple small intestine ulcers in a short time. We herein report the case of HCV with rapidly developing small intestine ulcers.

Management decision based on lymphovascular involvement leads to favorable outcomes after endoscopic treatment of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (MM) and submucosa up to 200 µm (SM1) has a risk of metastasis. The aims of this study were to investigate the long-term outcome of endoscopic submucosal dissection (ESD) for MM/SM1 ESCC and to assess the management after ESD in our hospital. METHODS: This was a retrospective cohort study conducted at a single institution. Patients with MM or SM1 ESCC who were treated with ESD were included. Additional prophylactic therapy was added if lymphovascular involvement (LVI) was noted in the ESD specimens. RESULTS: A total of 102 patients were analyzed. The median length of follow-up was 71.5 months (range 9 - 144 months) and the median number of CTs was 6 (range 0 - 24). LVI was found in 21 patients (20.6 %), and 12 patients underwent additional prophylactic therapy. The 5-year overall survival, disease-specific survival, and tumor-free survival rates were 84.1 %, 97.5 %, and 82.1 %, respectively. A total of 26 patients died, but only 2 of them died from ESCC. The cumulative metastasis rate was 11.8 %, and LVI was a significant predictor of metastasis (hazard ratio 5.42, 95 % confidence interval 1.39 - 21.18; P = 0.02). There were no differences between patients with MM ESCC and those with SM1 ESCC. CONCLUSIONS: The long-term outcome after ESD for MM/SM1 ESCC was favorable with additional prophylactic therapy and strict adherence to follow-up. These results indicate that our management decision based on LVI is a valid approach and that ESD can be offered as a therapeutic option to MM/SM1 ESCCs.

Effect of double platinum agents, combination of miriplatin-transarterial oily chemoembolization and cisplatin-hepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases.

Hepatocellular carcinoma (HCC) is one of the most common cancers and the third highest cause of cancer-associated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization (TOCE), and hepatic arterial infusion chemotherapy (HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

Spontaneous regression of hepatocellular carcinoma: A mini-review.

Spontaneous tumor regression is an extremely rare phenomenon in the oncology field. However, there are several case reports resulted in the regression of hepatocellular carcinoma (HCC) and the accumulation of clinical information and analyses of the mechanism can contribute to the development of a novel therapy. For this purpose, we have carefully reviewed 23 cases of spontaneously regressed HCC published in recent 5 years and our case. The information regarding the tumor size, tumor marker, treatments, etc., have been summarized. The mechanism of spontaneous regression has been discussed to date and presumed to be due to many factors, including hypoxia and immunological reactions. In this careful review of the 24 cases based on the clinical information, hypoxia, systemic inflammation, and both upon spontaneous regression were seen in 3, 8, and 4 cases, respectively among the 15 cases for which the information regarding the proposed mechanisms are available. Recent development of immunotherapeutic approaches in oncology shows promising results, therefore, accumulation of additional cases and analysis of mechanisms underlying the spontaneous regression of HCC are essential and could lead to the development of a new generation of immunotherapies including antibodies directed against immune reactions.

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial.

BACKGROUND: Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy. METHODS: Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded. RESULTS: The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = -0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE). CONCLUSIONS: The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve. TRIAL REGISTRATION: This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry ( http://www.umin.ac.jp/ctr/index.htm , UMIN000004691).

Increase of Soluble Programmed Cell Death Ligand 1 in Patients with Chronic Hepatitis C.

Objectives: To determine whether the soluble programmed cell death ligand 1 (sPD-L1) levels in patients with chronic hepatitis C (CHC) are associated with the clinical features of the disease and the efficacy of treatment, including interferon (IFN)-α. Methods: We investigated the sPD-L1 levels in the sera of 80 genotype 1b Japanese patients with CHC who underwent 12 weeks of telaprevir (TVR)- or simeprevir (SMV)-based triple therapy followed by 12 weeks of dual therapy with pegylated IFN-α plus ribavirin. Serum was also obtained from 22 patients with chronic hepatitis B (CHB) and from 10 healthy donors (HC). The sPD-L1 levels were measured using an ELISA kit. In addition, we examined the PD-L1 expression on the cell surface of immortalized hepatocytes (HPT1) after incubation with cytokines, including IFN-γ. Results: The pretreatment serum sPD-L1 levels were significantly increased in patients with CHC (median 109.3 pg/ml, range 23.1-402.3) compared with patients with CHB (69.2 pg/ml, 15.5-144.8; P <0.001) and HC (100.3 pg/ml, 40.1-166.6; P = 0.039). No significant differences in the sustained virological response (SVR) rates were found between the TVR- (85.0%, n=40) and SMV-treated (80.0%, n=40) groups, and the pretreatment levels of serum sPD-L1 were not significantly different between patients who achieved SVR (105.0 pg/ml, 23.1-402.3) and non-SVR patients (133.5 pg/ml, 39.9-187.2; P = 0.391). The pretreatment level of sPD-L1 was positively correlated with the alanine aminotransferase and alpha-fetoprotein levels (R2 = 0.082, P = 0.016, and R2 = 0.149, P = 0.002, respectively). Although immortalized hepatocytes do not express PD-L1, we confirmed that PD-L1 expression was induced after stimulation with IFN-γ. Conclusions: In this study, we first found that sPD-L1 was increased in patients with CHC. Our results indicate that the level of serum sPD-L1 might be associated with the progression of CHC and the generation of hepatocellular carcinoma.

Lusutrombopag increases hematocytes in a compensated liver cirrhosis patient.

A 56-year-old Japanese man with liver cirrhosis (LC) due to hepatitis C virus was admitted to our hospital for radiofrequency ablation of residual tumor following lusutrombopag administration. Laboratory tests revealed thrombocytopenia and leukopenia. The patient's LC was managed, and he was classified as Child-Pugh A. After admission, lusutrombopag was administered for 7 days. The platelet count increased to over 50,000/mm3 after 7-14 days and returned to previous levels 50 days after administration. Leukocyte and erythrocyte counts also increased in response to the treatment and stayed elevated for over 120 days. Lusutrombopag acts selectively on human thrombopoietin (TPO) receptors and activates signaling pathways that promote the proliferation and differentiation of bone marrow progenitor cells into megakaryocytes, consequently increasing the blood platelet count. However, the patient treated with lusutrombopag in our case study showed increased blood leukocyte and erythrocyte counts as well. Given that TPO receptors are reportedly expressed in not only megakaryocyte progenitor cells but also hematopoietic progenitors, lusutrombopag may potentially improve pancytopenia caused by LC and can be used for the recovery of blood counts before other treatments.

Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment.

Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately <1 y of survival from the time of diagnosis. A molecularly targeted drug, sorafenib, have been used to treat extrahepatic lesions and shown the prolonged survival time. However, the therapeutic benefit for the brain metastasis remains unclear, since it causes intratumor bleeding leading to the severe brain damage. No guidelines for the brain metastasis of HCC have been developed to date due to the shortage of the experiences and evidences. Therefore, the development of standard therapy for brain metastasis following the early diagnosis is essential by accumulating the information of clinical courses and evidences. For this purpose, we reviewed cases of HCC brain metastasis reported to date and analyzed additional 8 cases from our hospital, reviewing 592 advanced HCC cases to estimate the possible metastatic lesions in the brain. With careful review of cases and literature, we suggest that the cases with lung metastasis with increase tendency of tumor markers within recent 3-6 months have higher risks of brain metastasis. Therefore, they should be carefully followed by imaging modalities. In addition, the loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.

[Effective Prevention of Hand-Foot Syndrome by the Consumption of Dried Bonito Broth].

To examine whether the consumption of dried bonito both is effective for the prevention of hand-foot syndrome(HFS), concentrated bonito broth was administered to 10 patients with HCC who were treated with sorafenib. Among the 10 patients, seven showed an increase in peripheral blood flow, as observed on Doppler ultrasonography. Only one patient showed Grade 1 HFS on day 14 after the initiation of sorafenib (10%); this incidence rate of HFS was significantly lower than that obtained in our previous studies and reported data. These results suggest that consumption of dried bonito broth contributes to the prevention of HFS by maintaining peripheral blood flow.