Genomic analysis of an aggressive hepatic leiomyosarcoma case following treatment for hepatocellular carcinoma.

A 70-year-old man undergoing treatment for immunoglobulin G4-related disease developed a liver mass on computed tomography during routine imaging examination. The tumor was located in the hepatic S1/4 region, was 38 mm in size, and showed arterial enhancement on dynamic contrast-enhanced computed tomography. We performed a liver biopsy and diagnosed moderately differentiated hepatocellular carcinoma. The patient underwent proton beam therapy. The tumor remained unchanged but enlarged after 4 years. The patient was diagnosed with hepatocellular carcinoma recurrence and received hepatic arterial chemoembolization. However, 1 year later, the patient developed jaundice, and the liver tumor grew in size. Unfortunately, the patient passed away. Autopsy revealed that the tumor consisted of spindle-shaped cells exhibiting nuclear atypia and a fission pattern and tested positive for α-smooth muscle actin and vimentin. No hepatocellular carcinoma components were observed, and the patient was pathologically diagnosed with hepatic leiomyosarcoma. Next-generation sequencing revealed somatic mutations in CACNA2D4, CTNNB1, DOCK5, IPO8, MTMR1, PABPC5, SEMA6D, and ZFP36L1. Based on the genetic mutation, sarcomatoid hepatocarcinoma was the most likely pathogenesis in this case. This mutation is indicative of the transition from sarcomatoid hepatocarcinoma to hepatic leiomyosarcoma.

Efficacy of autologous platelet-rich plasma gel in patients with hard-to-heal diabetic foot ulcers: a multicentre study in Japan.

OBJECTIVE: To evaluate the healing outcome of a platelet-rich plasma (PRP) gel prepared using TKKT01 (a wound care device to prepare the PRP gel) in patients with hard-to-heal diabetic foot ulcers (DFUs) and who showed an inadequate response to ≥4 weeks of standard of care (SoC). METHOD: This open-label, single-arm, multicentre study was conducted in 15 centres in Japan. Eligible patients received PRP gel treatment twice a week for eight weeks, followed by a final evaluation after the completion of week 8 (day 57). The primary endpoint was the percentage of patients who achieved ≥50% reduction in wound radius at the final evaluation (achievement criterion, ≥60% of patients). Secondary endpoints included: wound area and volume reduction rates; time to possible wound closure by secondary intention; time to possible wound closure using a relatively simple procedure (e.g., skin graft and suture); and safety at the final evaluation. RESULTS: A total of 54 patients were included in the full analysis set, with 47 patients included in the per protocol set; the primary endpoint was met in 38/47 (80.9%) (95% confidence interval: 66.7-90.9%) patients who achieved ≥50% wound radius reduction at the final evaluation. High rates of wound area (72.8%) and volume (92.7%) reduction were observed at the final evaluation. The median time to possible wound closure by secondary intention and by use of a relatively simple procedure was 57 and 43 days, respectively. Complete wound closure at the final evaluation was achieved in 27 (57.4%) patients. No safety concerns were raised. CONCLUSION: In this study, the efficacy and safety of PRP gel treatment with TKKT01 in patients with hard-to-heal DFUs in Japan were confirmed by our findings. DECLARATION OF INTEREST: This study was funded by Rohto Pharmaceutical Co., Ltd., Japan. NO has been paid a consulting fee by Rohto Pharmaceutical Co., Ltd. KH is the Chief Medical Officer of Rohto Pharmaceutical. Co., Ltd. The other authors have no conflict of interest to declare.

A novel approach to diagnosing crystal-storing histiocytosis: utility of scanning electron microscopy for formalin-fixed paraffin-embedded tissue specimens.

Crystal-storing histiocytosis (CSH) is a rare disorder that shows infiltration of histiocytes with an aberrant cytoplasmic accumulation of crystalline structures and is often accompanied by lymphoproliferative-plasma cell disorders (LP-PCD) as background diseases. The diagnosis of CSH requires identification of crystalline structures that accumulate in the infiltrating histiocytes, which may be challenging by optical microscopy alone. In this case report, we describe an atypical course of systemic CSH with multifocal fibrosclerosis of an unknown background disease that was diagnosed by ultrastructural observation, including transmission electron microscopy (TEM) and scanning electron microscopy (SEM), in pathological autopsy. In addition, crystalline structures were successfully identified by scanning electron microscopic observations using formalin-fixed and paraffin-embedded (FFPE) tissue from biopsy specimens taken before death. Since CSH was identified by SEM in a tiny biopsy specimen, observation of histiocytic infiltrative lesions by SEM using FFPE tissue may lead to early detection of and initiation of treatment for CSH.

Further investigation of the rapid-onset and short-duration action of the G protein-biased µ-ligand oliceridine.

TRV130 (oliceridine), a G protein-biased ligand for µ-opioid receptor, has recently been synthesized. It is considered to have strong antinociceptive effects and only minor adverse effects. However, whether or not oliceridine actually exhibits an ideal pharmacological profile as an analgesic has not yet been fully clarified in animal studies. This study examined the pharmacological profile of oliceridine in cells and animals. Oliceridine (10 µM) did not produce any µ-opioid receptor internalization in cells even though it increased impedance, which reflects the activation of Gi protein using the CellKey™ system, and inhibited the formation of cAMP. In mice, oliceridine (0.3-10 mg/kg) produced a dose-dependent antinociceptive effect with a rapid-onset and short-duration action in the hot-plate test, as well as antihyperalgesia after sciatic nerve ligation without the development of antinociceptive tolerance using the thermal hyperalgesia test. On the other hand, oliceridine inhibited gastrointestinal transit. Furthermore, oliceridine produced rapid-onset hyperlocomotion at antinociceptive doses; sensitization developed in mice and an emetic effect was observed in ferrets. These results indicate that, although oliceridine may produce dopamine-related behaviors even through selective stimulation of the G-protein-biased µ-opioid receptor pathway, it still offers advantages for breakthrough pain without antinociceptive tolerance with adequate doses.

MicroRNA-196b is an independent prognostic biomarker in patients with pancreatic cancer.

Pancreatic cancer is a highly aggressive malignancy, with <50% patients surviving beyond 6 months after the diagnosis, and thus, there is an urgent need to explore new diagnostic and therapeutic approaches for this disease. Therefore, we conducted microRNA (miRNA) array analysis to detect miRNA molecules potentially associated with pancreatic cancer malignancy. To assess the identified miRNAs, we performed quantitative reverse transcription-PCR on 248 pancreatic ductal adenocarcinomas (UICC stage II). We also examined miRNA expression [microRNA-21 (miR-21) and microRNA-31 (miR-31)] and epigenetic alterations, including CpG island methylator phenotype (CIMP), potentially associated with the identified miRNAs. For functional analysis, we conducted proliferation and invasion assays using a pancreatic cancer cell line. miRNA array analysis revealed that microRNA-196b (miR-196b) was the most up-regulated miRNA in pancreatic cancer tissues compared with normal pancreatic duct cells. High miR-196b expression was associated with miR-21 (P = 0.0025) and miR-31 (P = 0.0001) expression. It was also related to poor prognosis in the multivariate analysis using overall survival (hazard ratio: 1.66; 95% confidence interval: 1.09-2.54; P = 0.019). Functional analysis demonstrated that miR-196b inhibitor decreased cell proliferation and that miR-196b mimic promoted cancer cell invasion. In conclusion, a significant association of high miR-196b expression with poor prognosis was observed in pancreatic cancer. Our data also revealed that miR-196b played an oncogenic role and that the transfection of the miR-196b inhibitor had an anti-tumour effect in the pancreatic cancer cell line. These results suggest that miR-196b is a promising diagnostic biomarker and therapeutic target in pancreatic cancer.

The effect of forced expression of mutated K-RAS gene on gastrointestinal cancer cell lines and the IGF-1R targeting therapy.

Mutation in K-RAS (K-RAS-MT) plays important roles in both cancer progression and resistance to anti-epidermal growth factor receptor (EGFR) therapy in gastrointestinal tumors. Insulin-like growth factor-1 receptor (IGF-1R) signaling is required for carcinogenicity and progression of many tumors as well. We have previously shown successful therapy for gastrointestinal cancer cell lines bearing a K-RAS mutation using an anti-IGF-1R monoclonal antibody. In this study, we sought to evaluate effects of forced K-RAS-MT expression on gastrointestinal cancer cell lines representing a possible second resistance mechanism for anti-EGFR therapy and IGF-1R-targeted therapy for these transfectants. We made stable transfectants of K-RAS-MT in two gastrointestinal cancer cell lines, colorectal RKO and pancreatic BxPC-3. We assessed the effect of forced expression of K-RAS-MT on proliferation, apoptosis, migration, and invasion in gastrointestinal cancer cells. Then we assessed anti-tumor effects of dominant negative IGF-1R (IGF-1R/dn) and an IGF-1R inhibitor, picropodophyllin, on the K-RAS-MT transfectants. Overexpression of K-RAS-MT in gastrointestinal cancer cell lines led to more aggressive phenotypes, with increased proliferation, decreased apoptosis, and increased motility and invasion. IGF-1R blockade suppressed cell growth, colony formation, migration, and invasion, and up-regulated chemotherapy-induced apoptosis of gastrointestinal cancer cells, even when K-RAS-MT was over-expressed. IGF-1R blockade inhibited the Akt pathway more than the extracellular signal-regulated kinase (ERK) pathway in the K-RAS-MT transfectants. IGF-1R/dn, moreover, inhibited the growth of murine xenografts expressing K-RAS-MT. Thus, K-RAS-MT might be important for progressive phonotype observed in gastrointestinal cancers. IGF-1R decoy is a candidate molecular therapeutic approach for gastrointestinal cancers even if K-RAS is mutated. © 2016 Wiley Periodicals, Inc.

Dynamics of L-Carnitine in Plasma and Urine in Patients Undergoing Cisplatin Chemotherapy.

BACKGROUND AND AIMS: Several studies have indicated that cisplatin (cis-diamminedichloroplatinum II; CDDP) causes urinary excretion of L-carnitine (LC). However, the underlying cofactors affecting the increased urinary excretion remain unclear. The present study was performed to evaluate the dynamics of LC in plasma and urine after CDDP chemotherapy and to examine the relations with clinical parameters, such as gender, body mass index (BMI), and renal function. METHODS: Twenty-two patients treated with CDDP therapy were selected. Blood and urine samples were taken from patients before starting CDDP treatment (day 0), on the next day (day 1), and on the seventh day (day 7). We measured plasma and urine concentrations of total, free, and acyl-LC, and examined the relationships with gender, age, treatment cycle, skeletal muscle mass, BMI, glomerular filtration rate, and change in creatinine concentration after CDDP administration. RESULTS: Both urinary and plasma concentrations of 3 types of LC increased markedly on day 1 and subsequently reverted to the pre-CDDP level on day 7. There was a positive correlation between the % changes in plasma and urine LC (correlation coefficient 0.59, p = 0.003) on day 1, but no significant relations were seen in other clinical parameters. CONCLUSIONS: CDDP transiently increased plasma LC levels. The mechanism seemed to involve recruitment for marked urinary loss of LC. However, these changes in plasma and urinary LC levels were not related to clinical factors, suggesting that the dynamics of LC were independent of preexisting physical parameters.

Mortality rates and walking ability transition after lower limb major amputation in hemodialysis patients.

OBJECTIVE: The number of hemodialysis patients with peripheral artery disease is increasing, and critical limb ischemia develops in some of these patients. The clinical outcomes in such patients after major amputation remain unclear. We therefore examined the mortality rates after major amputation in hemodialysis patients. METHODS: The study enrolled 108 hemodialysis patients undergoing their first major amputation at Community Health Care Organization Sendai Hospital between January 2005 and December 2014 and monitored them until June 2015. All-cause mortality and additional amputation-free survival were evaluated by Kaplan-Meier analysis. RESULTS: The most dominant primary disease of renal failure was diabetes mellitus (77%), and the duration of hemodialysis was 8.5 ± 6.8 years. During the median follow-up period of 11.5 months (20.3 ± 22.6 months), 80 patients (74%) died, and the survival rates were 83% at 30 days, 56% at 1 year, and 15% at 5 years. The median time to death was 19.9 months (95% confidence interval, 9.8-30.0 months), and the causes of death were cardiac (45%), sepsis (29%), cerebrovascular (4%), and others (22%). Thirty-one patients underwent additional amputation, and the additional amputation-free survival rates were 39% at 1 year and 9% at 5 years. The median time between the first and second amputations was 2.5 months (5.7 ± 7.6 months). Univariate analysis showed previous minor amputation (P = .04) and low hematocrit level (P = .04) were associated with the 30-day mortality rate, and age (P = .05) was associated with the 5-year mortality rate. On multivariate Cox proportional hazard analysis, only age was associated with mortality rate (hazard ratio, 1.02; 95% confidence interval, 0.99-1.02; P = .04). We also compared walking ability before and after major amputation among patients who survived >60 days. The rate changed from 34% to 12% for of ambulatory patients, from 45% to 48% for wheelchair use, and from 21% to 40% for bedridden patients. Ambulatory patients had a significantly better survival rate than the others (P = .02). CONCLUSIONS: The mortality rate after major amputation in hemodialysis patients was high, and major amputation had a huge negative effect on patients' walking ability.

Insulin-like growth factor-related components and the risk of liver cancer in a nested case-control study.

Insulin-like growth factor-1 (IGF1) is a potent mitogen. IGF-binding protein-3 (IGFBP3) binds and inhibits IGF1. High circulating IGF1 levels and low IGFBP3 levels are associated with increased risk of several cancers. We examined relationships between serum levels of these factors and hepatoma risk in a case-control study nested in a prospective cohort study (the Japan Collaborative Cohort Study (JACC Study)). A baseline survey was conducted from 1988 to 1990, and 39,242 subjects donated blood samples. Participants diagnosed with hepatoma by 1997 were considered cases for nested case-control studies. Ninety-one cases and 263 sex- and age-matched controls were analyzed. A conditional logistic model was used to estimate odds ratios (ORs) for the incidence of hepatoma associated with serum IGF1 and IGFBP3 levels. Neither IGF1 nor the molar ratio of IGF1/IGFBP3 was correlated with hepatoma risk. After adjustment for hepatitis viral infection, body mass index, smoking, and alcohol intake, a higher molar difference of (IGFBP3 - IGF1) was associated with a decreased hepatoma risk more than IGFBP3 alone (p for trend <0.001 and = 0.003, respectively). People in the highest quartile had a lower risk (OR = 0.098; 95 % confidence interval = 0.026-0.368). In subgroup analyses of males and females, the molar difference was associated with a decreased hepatoma risk (p for trend <0.05). In non-elderly individuals, the difference was inversely correlated with the incidence of hepatoma (p for trend <0.01). The molar difference of (IGFBP3 - IGF1) may be inversely associated with the incidence of hepatoma.

Development of κ Opioid Receptor Agonists by Focusing on Phenyl Substituents of 4-Dimethylamino-3-phenylpiperidine Derivatives: Structure-Activity Relationship Study of Matrine Type Alkaloids.

A series of new κ opioid receptor (KOR) agonists were developed from the lead compound 4-dimethylamino-1-pentanoylpiperidine (3), a matrine-type alkaloid. Derivatives of 3 were synthesized with a variety of phenyl substituents and evaluated for their antinociceptive effects. Additionally, their selectivity for an opioid receptor was investigated for cis-4c and d, and trans-4g, all of which had high activity exerted through the KOR.

Design and Synthesis of a Piperidinone Scaffold as an Analgesic through Kappa-Opioid Receptor: Structure-Activity Relationship Study of Matrine Alkaloids.

The matrine-type alkaloid 4-dimethylamino-1-pentanoylpiperidine (3a) has an antinociceptive effect through its impact on the κ-opioid receptor (KOR). Derivatives of 3a were synthesized by altering its amide and tertiary amine groups, and were evaluated for their antinociceptive effects. The results indicated that the distance between these groups on 3a was optimal for the antinociceptive effect. The effects obtained with compounds 8 and 9 indicated that the relative configuration of the 3- and 4-substituents influenced the effect mediated through the KOR.

A new classification of anterior talofibular ligament injuries based on ultrasonography findings.

BACKGROUND: Ultrasonography (US) has become a useful tool in the evaluation of thickness and continuity of damaged ligaments owing to the rapid advances in its performance and availability. Furthermore, US examination is economical and can be undertaken in a more timely manner than MRI, as it can be performed during the first patient visit. It is also likely to be more accurate than the traditional method of palpating ligaments to diagnose possible injury. The anterior talofibular ligament (ATFL) is most frequently injured of the lateral ankle ligaments and easy to depict on US. This study aimed to assess the treatment outcomes of lateral ankle ligament injuries using a new classification for ATFL injuries based on US findings. METHODS: A total of 140 acute lateral ankle ligament injuries in 132 patients (46 men, 86 women) treated non-operatively were evaluated retrospectively. The average age of the patients was 17.8 years (range, 7-57 years). Patients with a complaint of lateral ankle injury were examined using US, and the anterior talofibular ligament damage was classified into 5 types depending on the type of the injury. The treatment method was selected based on the ultrasonographic classification, and the clinical results were assessed by original evaluation and compared between treatment methods and classification types. RESULTS: A Good or Excellent treatment result was obtained in 133 out of 140 injuries (95.0%). Significant differences were observed in the distribution of treatment methods by injury type (P < 0.001), and the distribution of outcomes was significantly different from the uniform distribution (P < 0.001). Our findings demonstrate that the ultrasonographic classification proposed in this study can be used to determine the appropriate treatment resulting in good outcomes for all types of anterior talofibular ligament damage. CONCLUSION: Visualization of injured ligaments using US may introduce a novel approach of rating and treating ligament injuries.

Development of hypertension within 2 weeks of initiation of sorafenib for advanced hepatocellular carcinoma is a predictor of efficacy.

BACKGROUND: Sorafenib is an agent that inhibits vascular endothelial growth factor and is associated with onset or worsening of hypertension in some patients. We conducted a retrospective analysis of whether the development of hypertension during sorafenib treatment of advanced hepatocellular carcinoma could be a predictor of anti-cancer efficacy. METHODS: The study included 38 patients with advanced hepatocellular carcinoma who had received sorafenib for at least 1 month between January 2010 and December 2012. A retrospective analysis of the efficacy of sorafenib was conducted by dividing the patients into two groups-a hypertension group, presenting with grade 2 or higher hypertension according to the Common Terminology Criteria for Adverse Events (CTCTE) version 4.0; and a non-hypertension group, which included all other patients. This study evaluated the occurrence of hypertension within 2 weeks of initiation of therapy in order to avoid any treatment duration bias. Images were evaluated using the modified Response Evaluation Criteria in Solid Tumors. The response rate, time to progression, and overall survival were assessed. RESULTS: Twenty-two patients (58 %) developed grade 2 or higher hypertension within 2 weeks of initiation of therapy. The response rate was significantly higher in the hypertension group. Median time to progression was 153 days in the hypertension group versus 50.5 days in the non-hypertension group, which was significantly longer in the hypertension group. Moreover, median overall survival was 1,329 days in the hypertension group versus 302 days in the non-hypertension group, which was significantly longer in the hypertension group. CONCLUSIONS: Hypertension within 2 weeks of initiation of therapy may be a predictor of the anti-cancer efficacy of sorafenib when used for the treatment of advanced hepatocellular carcinoma.

[A Case of Long-Term Survival in a Patient with Colorectal Liver Metastasis Treated with Multidisciplinary Therapy].

A-71-year-old man underwent right hemicolectomy combined with partial resection of the small intestine and duodenum for an ascending colon carcinoma in July 2009. He presented with a liver metastasis adjacent to the inferior vena cava in November 2009. He received 6 courses of FOLFOX4, but the therapeutic effect was SD, so he underwent an extended posterior sectionectomy combined with partial S8 resection, inferior vena cava resection, and cholecystectomy. He developed remnant liver recurrence in February 2011 and another partial S8 resection was performed. He presented with remnant liver recurrence in October 2011, and radiofrequency ablation and systemic chemotherapy were performed, but were not effective. In June 2013, we performed an extended S8 segmentectomy combined with median hepatic vein and diaphragm resection. He is alive 2 years after the third hepatectomy without any recurrence. Although non-anatomical resection is often performed in repeat liver resections for colorectal liver metastases, sometimes detection of recurrent lesions in the same segment indicates Glisson invasion; therefore, anatomic resection may prolong long-term survival.

[Hepatocellular Carcinoma with Vp3 Tumor Thrombosis Treated with Multidisciplinary Treatment--Report of Two Cases].

Hepatic resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) at the bifurcation of the portal has the potential to cure the disease. Herein, we report 2 cases of HCC with Vp3 treated with a multidisciplinary approach that might include preoperative transcatheter arterial chemoembolization (TACE) or postoperative hepatic arterial infusion chemotherapy (HAIC). Case 1: A 73-year-old man was diagnosed with HCC with Vp3 located in segment 1 during follow up that was treated by performing a left hepatectomy with removal of the tumor thrombus. After surgery, the patient underwent HAIC, and he was alive without disease recurrence 2 years and 2 months after surgery. Case 2: A 77-year-old man with cirrhotic nonalcoholic steatohepatitis underwent liver resection followed by TACE. However, recurrent HCC with Vp3 was detected in segments 2 and 5, so we performed a repeat liver resection. The patient was alive without disease recurrence 1 year and 8 months after surgery without having received postoperative adjuvant chemotherapy. In select patients diagnosed with HCC with PVTT (Vp3/4), long-term survival can be obtained with multidisciplinary treatment such as surgery and preoperative TACE or postoperative HAIC.

Successful salvage chemotherapy with amrubicin for invasive thymoma associated with myasthenia gravis.

Anthracycline-based regimens with cisplatin have been commonly used for inoperable and relapsed thymoma. However, little information is available regarding the usefulness of salvage chemotherapy. Here, we describe a case of invasive thymoma associated with myasthenia gravis that showed a marked response to third-line chemotherapy, with single-agent amrubicin, a synthetic anthracycline analog and potent deoxyribonucleic acid topoisomerase II inhibitor. Amrubicin appears to have significant activity against invasive thymoma.

Forkhead box protein C2 contributes to invasion and metastasis of extrahepatic cholangiocarcinoma, resulting in a poor prognosis.

Extrahepatic cholangiocarcinoma (EHCC) is a cancer with a poor prognosis, and the postoperative survival of patients depends on the existence of invasion and metastasis. The epithelial-to-mesenchymal transition (EMT) is an important step in EHCC invasion and metastasis. Forkhead box protein C2 (FOXC2) is a transcription factor that has been reported to induce the EMT. Therefore we examined the correlation between FOXC2 expression and clinical pathological factors, and analysed the function of FOXC2. The expression of FOXC2 in 77 EHCC cases was investigated by immunohistochemical staining, and the relationship between FOXC2 expression and clinicopathological factor was assessed. Knockdown by small interfering RNA (siRNA) was performed to determine the roles of FOXC2 in EHCC cell line. FOXC2 expression correlated with lymph node metastasis (P = 0.0205). Patients in the high FOXC2 expression group had a poorer prognosis than the patients in the low FOXC2 expression group. Moreover, FOXC2 knockdown inhibited cell motility and invasion, and decreased the expression of EMT markers (N-cadherin, and matrix metalloproteinase (MMP) -2) and Angiopietin-2 (Ang-2). The EMT inducer FOXC2 contributes to a poor prognosis and cancer progression. FOXC2 may be a promising molecular target for regulating EHCC metastasis.

MR imaging of urinary bladder cancer for T-staging: a review and a pictorial essay of diffusion-weighted imaging.

Treatment decisions for bladder cancer patients are mainly based on the depth of bladder wall invasion by the tumor. In this article, we review the conventional MRI and exhibit a recently emerged diffusion-weighted imaging (DWI) of urinary bladder cancer for T-staging. We discuss limitations of conventional MRI, scanning protocols of DWI, normal pelvic findings on DWI, determination of T-stage using DWI, and pitfalls of DWI. DWI provides high contrast between bladder cancer and background tissue because the cancer shows markedly high SI. DWI has high sensitivity for detecting the stalk seen in stage Ta or T1. An inflammatory change or fibrosis surrounding the tumor mimics the invasion of bladder cancer on T2-weighted imaging or enhanced MRI and could lead to over-staging, but DWI could differentiate them clearly because these benign changes do not show high SI on DWI. DWI is also useful for detecting ureteral, urethral, and prostatic extension by means of the urethra. DWI provides more accurate information on the extent of bladder cancer and contributes to determination of the treatment strategy.

Synchronous colorectal liver metastasis in patients without node metastasis: possibility of localized liver metastasis.

BACKGROUND/AIMS: The liver is the most common distant site of metastasis from colorectal cancer and is often the only organ affected. We hypothesized that whether distant disease is localized in the liver or is a more systemic disease, may be important in the prognosis of patients with synchronous liver metastasis. The purpose of this study was to investigate the possibility of localized liver metastasis in cases with colorectal synchronous liver metastasis and without lymph node involvement. METHODOLOGY: Three hundred and twenty-five consecutive patients who underwent colorectal resection were identified for inclusion in this study, of which 24 cases with synchronous liver metastasis were detected. Of these, 11 who underwent curative simultaneous surgical resection of primary tumor and liver metastases were analyzed in this study. The clinical and pathological features of these cases were reviewed. RESULTS: Of the 11 patients with synchronous liver metastasis from colorectal cancer, 4 had disease recurrence, but none of those without regional node involvement had disease recurrence. In the multivariate analysis, only regional node metastases were significantly associated with disease recurrence. Recurrence-free interval by Kaplan-Meier curves differed significantly among patients with positive regional nodes. CONCLUSIONS: Our results imply that synchronous liver metastasis without regional lymph node metastasis is localized disease.

Usefulness of dual and fully automated measurements of cerebral blood flow during balloon occlusion test of the internal carotid artery.

BACKGROUND: This study was conducted to show the reliability of fully automated quantification of regional cerebral blood flow (rCBF) in balloon occlusion test (BOT) of the internal carotid artery (ICA). We also shows the usefulness of ratio of rCBF during BOT to rCBF at rest (BOT/rest ratio = rCBF during BOT/rCBF at rest) rather than asymmetry index (AI) during BOT (AI = occluded-side rCBF/contralateral rCBF). METHODS: In the last 2 years, we performed the BOT on 10 consecutive patients (4 with intracranial aneurysms and 6 with head and neck tumors). During the BOT, mean stump pressure (MSTP) of the ICA was monitored. We measured cerebral blood flow (CBF) with technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography at rest and during BOT. rCBF was determined using 3-dimensional stereotaxic region of interest template (3DSRT) which automatically divided CBF into 12 segments. We defined hypoperfusion segment as BOT/rest ratio <0.9 or AI <0.9. RESULTS: When the BOT/rest ratio was used as a hypoperfusion parameter, the number of hypoperfusion segments was significantly greater in patients with an MSTP ≤50 mm Hg than in patients with an MSTP >50 mm Hg. However, only AI during BOT did not reflect MSTP significantly. CONCLUSIONS: The evaluation of CBF changes in BOT using 3DSRT and the BOT/rest ratio were useful because of objective comparison.