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The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is still poor, and the 5-year survival rate in patients undergoing radical surgery (R0) is less than one-third. Since the prognosis depends mainly on tumor factors, so early diagnosis is necessary. To extend the survival time of these patients with a poor prognosis, cases of long-term survival were examined based on the results of our experiences and the literature. It was found that the hepatitis virus was highly involved in the carcinogenesis of ICC, and patients who were infected with hepatitis virus had rather good survival. J. Med. Invest. 68 : 15-21, February, 2021.

BACKGROUND The foci of distant metastasis from extramammary Paget’s disease (EMPD) are the lung, liver, truncal bones, vertebrae, and brain. However, skull metastases have not been reported. OBSERVATIONS The authors treated a patient with calvarial and skull base metastases from EMPD who had undergone wide local resection of EMPD 8 years before, and they report his clinical course. LESSONS Because EMPD with distant metastasis is fatal, it should be recognized that EMPD can metastasize to the skull even when it seemed to be in remission for several years.

Background : The aim of this study was to investigate quality of life (QOL) and night-time sleep disturbance in colon cancer patients with middle risk chemotherapy for proper antiemetic therapy. Methods : The study enrolled 139 patients with colorectal cancer. All patients received oxaliplatin or irinotecan-based chemotherapy. Patients completed a questionnaire about chemotherapy-induced nausea and vomiting and sleep disturbance. Sleep disturbance was checked, and the relationship between sleep disturbance and nausea was analyzed. Results : The prevalence of nausea was 48.9% (68 / 139). The degree of the nausea was slight / moderate / severe in 51 / 11 / 6 patients, and 12 patients had vomiting. Appetite showed no change / slightly decreased / half / one-fourth / none in 51 / 34 / 33 / 6 / 7 patients. There were significant differences in the mental component summary (MCS) score and the role-social component score (RCS). (MCS : nausea(+) vs nausea(-) 46.4 ± 1.1 vs 54.1 ± 1.1 p 0.01 RCS : nausea(+) vs nausea(-) 33.1 ± 2.1 vs 41.6 ± 2.1 p 0.01). Using the MCS with a cut-off score of 50, patients were divided into two groups, and nausea was significantly correlated with a low MCS score. Furthermore, patients were divided into two groups using a Pittsburgh Sleep Quality Index cut-off score of 6, and sleep disturbance was correlated with old age and second-line chemotherapy. Conclusions : Nausea affects QOL and night-time sleep of colon cancer patients with middle risk chemotherapy. J. Med. Invest. 67 : 338-342, August, 2020.

Purpose Carotid artery stenting (CAS) is a valuable alternative to carotid endarterectomy, especially in high-risk patients. However, the reported incidences of perioperative stroke and death remain higher than for carotid endarterectomy, even when using embolic protection devices (EPDs) during CAS. Our purpose was to evaluate 30-day major adverse events after CAS when selecting the most appropriate EPD. Methods We reviewed the clinical outcomes of 61 patients with 64 lesions who underwent CAS with EPDs. Patients who underwent CAS associated with thrombectomy and who had a preoperative modified Rankin scale score >3 were excluded from the analysis. The EPD was selected based on symptoms, carotid wall magnetic resonance imaging and lesion length, and we analyzed combined 30-day complication rates (transient ischemic attack, minor stroke, major stroke or death). Results Forty-nine patients were men and 12 were women. The median age was 72 years (range: 59–89 years) and 44 lesions were asymptomatic. A filter-type EPD was selected in 23 procedures, distal-balloon protection in 14 procedures and proximal-occlusive protection in 27 procedures. Two patients (3.1%) experienced a transient ischemic attack and one patient (1.6%) had a minor stroke within 30 days of the procedure. No patients experienced procedure-related morbidities (modified Rankin score >2) or death. Conclusions The perioperative stoke rate was low when we selected a proximal-occlusive-type EPD in high-risk patients with vulnerable carotid artery disease. Our algorithm for EPD selection was an effective tool in the perioperative management of carotid artery stenosis.

We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 + oxaliplatin + bevacizumab). This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m2/day on days 1–5, 8–12, 15–19, and 22–26) and infusions of oxaliplatin (50 mg/m2 on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 + oxaliplatin + bevacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate.

Background Solitary fibrous tumor (SFT) is a prototypical mesenchymal neoplasm that induces non-islet cell tumor hypoglycemia (NICTH) due to overproduction of insulin-like growth factor 2 (IGF2). We here report the case of a malignant SFT associated with a hypoglycemia attack. Case presentation An 81-year-old man with a large subphrenic mass presented with hypoglycemia and loss of consciousness. His serum insulin and IGF1 levels were relatively low, suggesting an excessively high serum IGF2 levels. Preoperative Western blotting of serum confirmed the overproduction of high-molecular-weight IGF2. After total tumor resection, the patient recovered from hypoglycemia without the need for further treatment. Histological examination revealed proliferation of spindle cells and frequent nuclear mitoses with STAT6 and CD34 immunoreactivity, which led to the diagnosis of malignant SFT. IGF2 was strongly upregulated in the tumor upon immunohistochemistry, consistent with the report of NICTH. In addition, the tumor expressed IGF2 receptor (IGF2R) but not IGF1R. Conclusions The present results indicate that the tumor co-expressed IGF2 and IGF2R. IGF2R has not previously been recognized as a tyrosine kinase receptor participating in cell signal transduction. Thus, further case series are required to determine whether IGF2R overexpression reflects the action of an unknown autocrine/paracrine system involving IGF2 for cell proliferation or for the scavenging and degradation of IGF2.

Heat shock proteins (HSPs) are rapidly synthesized into cells in response to various types of physical or chemical insults and induce potent resistance to the stressors. A stress-inducible HSP70 is not expressed in normal conditions, but once HSP70 is excessively induced under various environmental stresses, HSP70-expressing cells can survive even under lethal conditions. In this review, we focused on the potential role of HSPs particularly HSP70 in liver surgery. A non-toxic HSP70 inducer, geranylgeranylacetone (GGA), has been introduced to exert a potent cytoprotective action against liver injury after ischemia/reperfusion, massive hepatectomy and liver transplantation in animal experiments. We have tried to explain possible therapeutic benefits of GGA in liver surgery. However, any dependable clinical application has not been done. One of the reasons is that any randomized clinical trial has not being carried out in clinical cases. Therefore, we have advocated the national scale randomized clinical trial for dependable clinical application of GGA.

Purpose: Endovascular therapy for emergent large vessel occlusion has been established as the standard approach for acute ischaemic stroke. However, the effectiveness and safety of endovascular therapy in the very elderly population has not been proved. Objective: To determine the safety and effectiveness of endovascular therapy in octogenarians and nonagenarians. Methods: We retrospectively reviewed all patients who underwent endovascular therapy at two stroke centres between April 2012 and July 2018. Functional outcome was assessed using the modified Rankin scale at 90 days after stroke or at discharge. A favourable outcome was defined as a modified Rankin scale score of 0–2 or not worsening of the modified Rankin scale score before stroke. Outcome was compared between younger patients (aged 46–79 years, n = 40) and octogenarians and nonagenarians (aged 80–97 years, n = 19). Results: Octogenarian and nonagenarian patients had pre-stroke functional deficit (modified Rankin scale score >1) more frequently than younger patients (57.9% vs. 20.0%, respectively, P = 0.0059). No difference was observed between very elderly and younger patients in the rate of successful reperfusion (89.5% vs. 67.5%, respectively, P = 0.11), favourable functional outcome (47.4% vs. 45.0%, respectively, P = 1.00) and mortality (21.1% vs. 27.5%, respectively, P = 1.00). On multiple regression analysis, successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were independent predictors of favourable outcome ( P = 0.0003, 0.015 and 0.028, respectively). Conclusions: Successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were clinical predictors of favourable outcome. However, we did not observe an age-dependent effect of clinical outcome after endovascular therapy.

BACKGROUND AND AIM Various randomized clinical studies have suggested that short- and long-term outcomes of laparoscopic surgery (LAP) for colorectal cancer are comparable with those of open surgery (OP). However, these studies were performed in high-volume hospitals. The aim of the present study was to compare the outcomes of LAP versus OP for colorectal cancer in rural hospitals. METHODS This was a multicenter retrospective propensity score-matched case-control study of patients who underwent colorectal surgery from January 2004 to April 2009 in 10 hospitals in Japan. All patients underwent curative surgery for pathologically diagnosed stage II or III colorectal cancer. The primary end point was 5-year overall survival (OS). The secondary end points were disease-free survival (DFS) and postoperative complications. RESULTS In total, 319 patients who underwent LAP and 1020 patients who underwent OP were balanced to 261 pairs. There was no significant difference in the OS and DFS between two groups. The operation time was significantly shorter for OP than for LAP. Blood loss was significantly lower in LAP than in OP. There was no difference in intraoperative morbidity between the two groups. The postoperative morbidity was significantly lower in LAP than in OP. The hospital stay was significantly shorter in LAP than in OP. There was no significant difference in 90-day postoperative mortality. CONCLUSIONS Laparoscopic surgery may be a feasible option for colorectal cancer in rural hospitals.

Patient: Male, 57-year-old Final Diagnosis: Leptomeningeal carcinomatosis Symptoms: Headache • visual acuity loss Medication: — Clinical Procedure: Venous sinus stenting Specialty: Oncology Objective: Unusual or unexpected effect of treatment Background: Cerebral venous sinus obstruction associated with leptomeningeal carcinomatosis is an extremely rare complication of advanced non-small-cell lung cancer. There is little information available on the efficacy of therapeutic options because of its rarity and extremely poor prognosis. Case Report: A 57-year-old man presented with severe headache, vomiting, and visual loss for 1 month. Head magnetic resonance venography (MRV) showed occlusion of the left transverse sinus. Gd-enhanced MRI showed no abnormal enhancement. Lumbar puncture intracranial pressure was higher than 40 cmH2O. Positive cerebrospinal fluid tumor cytology confirmed the diagnosis of leptomeningeal carcinomatosis (LC). The headache was relieved by repeated lumbar punctures, and ventriculo-peritoneal shunt was performed. Cerebral angiography showed severe stenosis of the left transverse sinus without thrombosis, and significant delay of cerebral circulation. The transverse sinus stenosis was judged to be contributing to raised intracranial pressure, and the patient underwent left transverse sinus stent placement. After the procedure, his visual acuity improved, the visual field was enlarged, and his headache could be controlled by medication. Follow-up Gd-enhanced MRI showed dural enhancement and spinal dissemination. Because molecular biology of the surgical specimen showed epidermal growth factor receptor (EGFR)-activating mutations, he was treated with osimertinib for 2 months. He survived for 8 months following the diagnosis of LC and left transverse sinus stenosis. Conclusions: Venous sinus stenting can offer an effective palliative interventional option for symptom relief of severe headache and visual symptoms, even in the end stage of malignancy.

Objective To determine the safety and effectiveness of emboli protection during carotid artery stenting (CAS). Methods The clinical outcomes of 59 patients who underwent CAS with emboli protection devices were reviewed. Patients who underwent CAS associated with thrombectomy and who had preoperative mRS >3 were excluded from the study. 46 patients were male, and 13 were female. The median age was 72.5 years (range 59–89), and 44 lesions were asymptomatic. Emboli protection device was selected based on the presence of symptom, carotid wall MRI, and lesion length. The combined 30 day complication rates (transient ischemic attack, minor stroke, major stroke, or death) were analyzed. Results Filter-type emboli protection device was selected in 23 procedures, distal balloon protection in 16 procedures, and proximal occlusive protection in 21 procedures. Our patients (6.8%) experienced a transient ischemic attack, and one patient (1.7%) had a minor stroke within 30 days of the procedure. No patients experienced procedure-related morbidities (mRS >2) or deaths. Conclusions Our data suggest that algorithmic selection of emboli protection based on the presence of symptom, carotid wall MRI, and lesion length can be effective in the prevention of major ischemic adverse events. Disclosures Y. Kawabata: None. N. Nakajima: None. H. Miyake: None. S. Fukuda: None. T. Tsukahara: None.

Phase-contrast magnetic resonance angiography (PC-MRA) is useful for the quantitative measurement of blood flow volume (BFV) in the internal cerebral arteries (ICAs) and basilar artery (BA). A 45-year-old man was diagnosed with a non-hemorrhagic high-flow arteriovenous malformation (AVM) in the right temporal lobe. PC-MRA examinations of the bilateral ICAs and BA were conducted before treatment, at five days and at one and three months after the operation. The patient underwent preceding endovascular embolization of the deep part of the nidus and feeders. There were numerous feeders from the superior MCA trunk, which directly passed through the nidus to the normal brain. Therefore, the nidus was completely removed while maintaining the flow of the main superior MCA trunk in a passing artery. The BFV of the right ICA before AVM treatment was extremely high (mean: 675.7, systolic: 896.1, diastolic: 518.5 mL/min). Five days after the nidus resection, the BFV of the right ICA was decreased by almost half of that before treatment, and it was decreased even more at one month after the operation. The BFVs of the left ICA and BA were slightly increased before the operation and returned to normal values after the operation. The diastolic total BFV was immediately decreased after the operation, but the systolic total BFV was not sufficiently decreased at five days after the operation. Therefore, the difference between these systolic and diastolic total BFVs was higher at five days after the operation than before the operation. The systolic and diastolic total BFVs were decreased to normal levels one month after the operation. PC-MRA is a convenient and useful tool for quantifying BFVs in AVMs and can help plan the treatments. More research is needed to establish a definite role for PC-MRA in the quantification of flow changes in the treatment of high-flow AVMs.

Background The recurrence rate of chronic subdural hematoma (CSDH) after trepanation is relatively high and involves various factors. We encountered an extremely rare case in which metastasis of an extracranial malignant tumor to the hematoma capsule was thought to be causing short-term repeated recurrences of CSDH. Case Description The patient was a 74-year-old man who had undergone bur hole evacuation of left CSDH 7 months earlier and had been receiving chemotherapy for stage IV gastric cancer for the preceding 6 months. He presented with symptoms of right hemiparesis and was diagnosed with left CSDH. Bur hole evacuation was performed twice, but the hematoma enlarged again both times within a short period. A third bur hole evacuation was performed after middle meningeal artery embolization, but the hematoma again enlarged shortly thereafter. Hematoma enlargement was finally suppressed by extracting the hematoma capsule under craniotomy. In histopathologic examinations, hematoxylin-eosin staining showed poorly differentiated adenocarcinoma primarily along the luminal side of the hematoma capsule and immunohistochemical staining showed results identical to findings from the existing gastric cancer. Pathologic results confirmed metastasis of the gastric cancer to the hematoma capsule, and this was considered to be the cause of short-term repeated recurrence of CSDH. Conclusions To the best of our knowledge, this is the first report of metastasis to a hematoma capsule originating from an extracranial malignant tumor. The clinical course in the present case suggests metastasis of extracranial malignant tumor to the CSDH capsule as an extremely rare cause of recurrence.

Purpose Simple rating scale for calcification in the cervical arteries and the aortic arch on multi-detector computed tomography angiography (MDCTA) was evaluated its reliability and validity. Additionally, we investigated where is the most representative location for evaluating the calcification risk of carotid bifurcation stenosis and atherosclerotic infarction in the overall cervical arteries covering from the aortic arch to the carotid bifurcation. Method The aortic arch and cervical arteries among 518 patients (292 men, 226 women) were evaluated the extent of calcification using a 4-point grading scale for MDCTA. Reliability, validity and the concomitant risk with vascular stenosis and atherosclerotic infarction were assessed. Results Calcification was most frequently observed in the aortic arch itself, the orifices from the aortic arch, and the carotid bifurcation. Compared with the bilateral carotid bifurcations, the aortic arch itself had a stronger inter-observer agreement for the calcification score (Fleiss’ kappa coefficients; 0.77), but weaker associations with stenosis and atherosclerotic infarction. Calcification at the orifices of the aortic arch branches had a stronger inter-observer agreement (0.74) and enough associations with carotid bifurcation stenosis and intracranial stenosis. In addition, the extensive calcification at the orifices from the aortic arch was significantly associated with atherosclerotic infarction, similar to the calcification at the bilateral carotid bifurcations. Conclusions The orifices of the aortic arch branches were the novel representative location of the aortic arch and overall cervical arteries for evaluating the calcification extent. Thus, calcification at the aortic arch should be evaluated with focus on the orifices of 3 main branches.

Summary Background & aims A late evening snack (LES) is recommended for improving starvation state in cirrhotic patients. The non-protein respiratory quotient (npRQ) is an important index for evaluating the indications and effectiveness of LES. Indirect calorimetry is used to determine npRQ, but it is expensive and not available in many hospitals. The aim was to find blood biochemical markers reflecting npRQ. Methods A total of 183 cirrhotic patients (M/F = 149/34) were enrolled. For each patient, fasting state npRQ was determined by indirect calorimetry. The relationships between npRQ and indices such as age, body mass index, platelet count, etiology, and levels of aspartate aminotransferase, alanine aminotransferase, total bilirubin, albumin, blood glucose, and non-esterified fatty acid (NEFA) were statistically analyzed. Results There was a significant negative correlation between the measured npRQ and serum NEFA levels, and the NEFA level was the strongest predictor of npRQ. Multiple regression analysis identified that the NEFA and Hepatitis B virus were predictors of npRQ. Conclusion These data suggest that fasting serum NEFA level is the most relevant biomarker to determine npRQ if indirect calorimetry is unavailable. Thus, serum NEFA levels may be useful to determine the indications and effectiveness of LES therapy in cirrhotic patients.

A 67-year-old woman suffered from severe aortic stenosis and atrial fibrillation, and underwent aortic valve replacement with a St. Jude Medical Regent 23-mm valve and pulmonary vein isolation using an AtriCure Isolator Synergy.At 6 days after the operation, she experienced sudden onset of atrial fibrillation, left side paralysis, and dysarthria. Right internal carotid artery embolism was diagnosed via magnetic resonance imaging, and we promptly performed neuroendovascular therapy with a Solitaire FR. Neuroendovascular treatment succeeded, and her neurological function was restored to near-normal. Her post-treatment course was uneventful, and she is currently well without neurological dysfunction.

Introduction Histone deacetylase (HDAC) plays an important role in chromatin remodeling and gene expression, and in regulating cell cycle progression and differentiation. Furthermore, hypoxic conditions in the malignant tumor enhance HDAC function and increased HDAC activity is closely involved in worse malignant behavior through hypoxia inducible factor (HIF) activation. The aim of this study was to elucidate the correlation between HDAC expression and tumor malignant behavior including HIF-1α expression in intrahepatic cholangiocarcinoma (IHCC). Methods Thirty-five patients with IHCC who underwent hepatic resection were evaluated. HDAC1 and HIF-1α expressions were determined immunohistochemically, and the patients were divided into 2 groups: the HDAC1 positive group ( n = 21) and the HDAC1 negative group ( n = 14). Clinicopathologic variables including HIF-1α expression were compared between the 2 groups. Results HDAC1 expression correlated significantly with higher stage carcinoma, lymph node metastasis, and vascular invasion. The prognosis in the HDAC1 positive group was poorer than in the HDAC1 negative group (5-year survival: 78% vs 8%, P = .001). Furthermore, disease free survival rate in the HDAC1 positive group had significantly worse than that in the HDAC1 negative group ( P = .0003). In the multivariate analysis, HDAC1 positive expression was identified as the only independent prognostic factor for disease free survival (Hazard Ratio: 7.194, P = .0018). Furthermore, there was a significant correlation between HDAC1 expression and HIF-1α expression ( P = .007). Conclusion These findings suggested that HDAC1 positive expression was a potential new prognostic indicator of IHCC, and a possible promising molecular target through the regulation of HIF-1α.

Aim: The aim of this study was to investigate the characteristics of super-elderly hepatocellular carcinoma (HCC) patients aged 80 years or more who underwent hepatectomy and to clarify whether elderly patients with HCC benefit from hepatectomy. Methods: Between March 1992 and December 2008, 278 patients who underwent curative hepatectomy for HCC were investigated. Super-elderly patients were defined as those aged 80 years or more. Clinicopathological data and outcomes after hepatectomy were compared between super-elderly and non-super-elderly groups. Results: Preoperative parameters, such as biochemical examinations, and liver function tests in the non-super-elderly group were comparable with those of the super-elderly group (n = 11). Exceptionally, albumin level in the super-elderly group was lower than that in the non-super-elderly group (P = 0.03). Surgical data and the prevalence of postoperative complications did not differ significantly between the two groups. No mortality was observed in the super-elderly and non-super-elderly group. Conclusions: Hepatectomy for HCC was a feasible option even in super elderly patients aged 80 years or older with accurate selection.

Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are important enzymes in the metabolism of 5-fluorouracil and possible predictive markers. We conducted this study to clarify if TS and DPD gene expressions are a prognostic indicator for intrahepatic cholangiocarcinoma (IHCC).The subjects of this study were 21 patients with IHCC who had undergone surgical resection. Intratumoral TS and DPD mRNA expressions were examined using the Danenberg tumor profile method and classified into two groups according to the median value of each. We then compared the clinicopathological variables, including prognosis, between the high and low expression groups.Low DPD expression was correlated with macroscopic type, namely, mass-forming + infiltrative (P = 0.08). Postoperative survival rates in the low DPD expression group were significantly lower than those in the high DPD expression group. Multivariate analysis revealed macroscopic type to be an independent prognostic factor, whereas TS mRNA expression did not correlate with any clinicopathological variables, including prognosis.Low DPD mRNA expression was related to macroscopic type and associated with poor prognosis. DPD mRNA expression in tumor cells is suggested to be an important regulator of malignant behavior in IHCC.

To investigate the prognostic factors of peripheral-type intrahepatic cholangiocarcinoma (PP-IHCC) and evaluate the surgical outcomes according to surgical strategy alterations. Twenty-two patients were divided into two groups according to the surgical strategy: an extended surgery group (Ex group: n = 10), composed of those who underwent hepatic lobectomy combined with lymph node (LN) dissection and bile duct resection; and a customized surgery group (Cx group: n = 12), composed of those who underwent hepatectomy and bile duct resection according to tumor spread. LN dissection was not performed in patients without LN metastasis. Multivariate analysis revealed that R2 resection, LN metastasis, and intrahepatic metastasis were independent prognostic factors. LN dissection was significantly infrequent in the Cx group. Survival after curative resection was similar in the two groups (3-year survival: 42.9 vs. 57.1%). Liver metastasis was the most frequent primary recurrence, occurring in more than 80% of patients from both groups. Curative surgery might improve the prognosis of patients with PP-IHCC, but routine LN dissection is not recommended, particularly for patients without LN metastasis. Surgery alone, including LN dissection, cannot control this type of tumor, and additional treatment should be given.

We describe a new technique of ultrasound (US)-guided microwave coagulation (MC) of the Glissonean pedicle, performed before transection to control the inflow and select the resection area. This report introduces our procedure and evaluates the outcomes of patients treated using this technique.The Glissonean pedicles feeding the segment or cone unit were coagulated by US-guided MC, after which transection was performed. We used this US-guided MC technique to perform anatomical resections in 12 patients with hepatocellular carcinoma (MC group). We compared the outcomes of this group with those of a historical group of 10 patients who underwent conventional hepatectomy (control group). The two groups were well matched for age, tumor size, location, and type of hepatectomy.The mean operative times were similar, but the mean blood loss was significantly lower the in MC group than in the control group. Recurrence developed in four patients from the MC group, but local recurrence was not observed. Bile leakage occurred in one patient from the MC group, but the incidences of postoperative complications did not differ between the groups.Our procedure allows anatomical resection to be performed safely and easily, and helps prevent intrahepatic metastasis via portal flow during the transection.

The purpose of this study was to clarify the clinical predictors of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH).102 patients with ruptured cerebral aneurysms were treated (77 by clipping and 25 by coiling). 40 patients were male and 62 were female. Median age was 59 years (range 31-88). The modified Rankin Scale was used to assess functional outcomes 3 months after treatment or at discharge. The associations between potential clinical risk factors and DCI after SAH were assessed using the χ(2) test.52 patients (51.0%) had a good outcome and 13 patients (12.7%) died despite treatment. DCI was observed in 26 patients and hydrocephalus was observed in 37 patients. There were marginal differences in clinical outcomes between the treatment groups (p=0.053), mainly because functional outcomes were significantly superior in the coiling group (p=0.04) in patients with severe SAH. DCI was seen less frequently in the coiling group than in the clipping group (4.0% vs 32.4%, p=0.001). The presence of hydrocephalus was significantly associated with the occurrence of DCI (p0.001). Multivariate logistic regression analysis also showed that the treatment modality and the presence of hydrocephalus were independent risk factors for DCI.DCI was less frequently observed in the coiling group, and clinical outcomes were also superior in the coiling group, especially for patients with severe SAH. The results showed a significant correlation between DCI and hydrocephalus.

症例は65歳，女性．腹痛，食思不振，貧血を認め，当院紹介となった．腹部画像検査で，下腹部の巨大な腫瘤と肝内に1cm大の腫瘤を認めた．回腸腫瘍，肝転移疑いの術前診断のもと手術を行った．術中所見として多発肝転移を認め，回盲部切除術，肝転移生検，肝転移巣のラジオ波焼灼術を施行した．摘出された腫瘍は最大径16cmであり，組織学的には胞巣状，索状に増殖する未分化な腫瘍細胞を認め，免疫組織学的診断で内分泌細胞癌と判断した．また一部に高分化腺癌を認め，以上より腺内分泌細胞癌の診断に至った．小腸内分泌細胞癌の本邦報告例は自験例を含めて16例であり，経過から非常に予後不良な癌と示唆された．本疾患の有効な治療法は確立されておらず，今後の症例の集積が必要である．

Acute liver failure after massive hepatectomy remains a challenging problem. In this study, using a microarray designed to monitor the side effects of drugs, we examined changes in gene expression in the remnant liver during the 24 h after hepatectomy and the effects of a nontoxic heat shock protein (HSP) 70 inducer, geranylgeranylacetone (GGA), after 90% hepatectomy in rats. A single oral administration of 100 mg/kg GGA significantly suppressed the release of aminotransferases and improved survival compared with vehicle administration. The hepatectomy upregulated 74 genes and downregulated 95. Interestingly, ten cytokine genes were upregulated, while no cytokine-related gene was downregulated. Among the ten cytokine genes, a potent chemoattractant for neutrophils, GRO1, was most rapidly and markedly upregulated after 90% hepatectomy. GGA effectively suppressed the up-regulation of GRO1 messenger ribonucleic acid, and this was validated by Northern hybridization. Microarray and immunoblot analyses showed that, in addition to HSP70 and HSP27, GGA preferentially induced an endoplasmic reticulum chaperone, BIP. Considering hemodynamic and metabolic overloading as a primary cause of acute lever failure, the ER stress response enhanced by GGA may also play an important role in the prevention of overload-induced liver damage.

Various randomized clinical studies have suggested that short- and long-term outcomes of laparoscopic surgery (LAP) for colorectal cancer are comparable with those of open surgery (OP). However, these studies were performed in high-volume hospitals. The aim of the present study was to compare the outcomes of LAP versus OP for colorectal cancer in rural hospitals.This was a multicenter retrospective propensity score-matched case-control study of patients who underwent colorectal surgery from January 2004 to April 2009 in 10 hospitals in Japan. All patients underwent curative surgery for pathologically diagnosed stage II or III colorectal cancer. The primary end point was 5-year overall survival (OS). The secondary end points were disease-free survival (DFS) and postoperative complications.In total, 319 patients who underwent LAP and 1020 patients who underwent OP were balanced to 261 pairs. There was no significant difference in the OS and DFS between two groups. The operation time was significantly shorter for OP than for LAP. Blood loss was significantly lower in LAP than in OP. There was no difference in intraoperative morbidity between the two groups. The postoperative morbidity was significantly lower in LAP than in OP. The hospital stay was significantly shorter in LAP than in OP. There was no significant difference in 90-day postoperative mortality.Laparoscopic surgery may be a feasible option for colorectal cancer in rural hospitals.

Background This study aimed to investigate regulatory mechanisms of hepatocyte proliferation by comparing liver regeneration of the remnant lobe after 70% partial hepatectomy (PH) and portal vein branch ligation (PBL) in rat. Methods Expressions of activins βA, βC, and βE and their receptors were investigated after PH and PBL. The proliferating cell nuclear antigen (PCNA) labeling index was used to monitor hepatocyte proliferation. Results The PCNA labeling index in the regenerative lobe of PBL rats reached a peak at 48 h, a delay of 24 h compared with the remnant lobe in PH rats. In the postoperative early stage, the expression of activin βA, βC, and βE mRNAs was stronger in PBL than PH. At 72 h the expression of activin receptor type IIA mRNA reached a peak in PH but was significantly lower in PBL. Conclusions Hepatocyte proliferation, and the regulated expression of activins and their receptors, differs during liver regeneration after PH and PBL in the rat. Thus, regulation of activin signaling through receptors is one of the factors determining liver regeneration after PH and PBL.

A superoxide-producing enzyme, NADPH oxidase 1 (Nox1), dominantly expressed in the colon, is implicated in the pathogenesis of colon cancer. Immunohistochemistry showed that Nox1 was constitutively expressed in surface mucous cells. Adenomas and well differentiated adenocarcinomas up-regulated Nox1 expression. Ki-67-negative, well differentiated tumor cells contained abundant Nox1, whereas Ki-67-positive, proliferating cells did not express it. This differentiation-dependent expression in normal as well as tumor tissues suggests distinct roles of Nox1 besides mitogenic function. Nuclear factor (NF)-kappaB was predominantly activated in adenoma and adenocarcinoma cells expressing abundant Nox1, suggesting that Nox1 may stimulate NF-kappaB-dependent antiapoptotic pathways in colon tumors.

We report a patient with duodenal varices oozing blood who had undergone low anterior resection of the rectum and resection of the liver tumor because of multiple liver metastasis from rectal cancer 80 months previously. Although endoscopic variceal ligation (EVL) was carried out for the ruptured duodenal varices, their bleeding persisted and hepatic encephalopathy also appeared. Finally, balloon occluded retrograde transvenous obliteration (BRTO) with percutaneous transhepatic obliteration (PTO) was carried out for the duodenal varices. Percutaneous transhepatic portography revealed detailed hemodynamics. Following PTO, the duodenal varices were stagnated by BRTO, and no complications were recognized. No re-bleeding episode has been observed since the treatment. In addition, the hepatic encephalopathy was also improved.

Background : The prognosis of liver transplantation for liver cancer is determined by recurrence in the liver graft. In this study, the effects of immunosuppressors, FK506 and cyclosporine A (CsA) on the migration of liver cancer cells were investigated. Methods : The effects of FK506 at concentrations of 1-100 ng/mL and CsA at 1-1000ng/mL on the growth of poorly and well differentiated human hepatocellular carcinoma cell lines, HLE and HuH-7, respectively, were examined. After treatment of these cells with FK506 and CsA, the growth of these cells, their cytotoxicities and invasion assay on the Matrigel basement membrane invasion chamber were evaluated. In addition, the effects of FK506 and CsA on the changes in the production of a soluble intercellular adhesion molecule-1 (sICAM-1) of these cells were measured. Results : FK506 and CsA at concentrations of 1-10 ng/mL inhibited the growth of both HLE and HuH-7 and those immunosuppressors at concentrations over 100 ng/mL exhibited cytotoxicity on these cells. FK506 at concentration of 1ng/mL significantly inhibited the invasion of poorly differentiated HLE, but not well differentiated HuH-7, after treatment for 2-5 days in culture (p

To investigate the lymph network change in pancreatic duct obstruction in pigs as a model of pancreatic cancer invading pancreatic duct, six domestic pigs weighing 17-40 kg underwent surgery as protocol. Two of them were controls, and the others underwent ligation of the pancreatic duct as a model of ductal obstruction. A CH 40 and lipiodol mixture was injected in their pancreas at 7 or 21 Days after first operation. Radiographic examination had been also performed. Five or 14 days later, they were examined radiographically, and sacrificed for histological examination. Ligation of the pancreatic duct caused experimental pancreatitis. Dilatation of the pancreatic duct and dilatation of the lymph canal in the interlobular space of pancreas was demonstrated in the ligation group. CH 40 and lipiodol showed discrepancies in the distribution. There were not distinct differences between the two groups in a route of CH 40 traveling. Only fluoroscopic examination revealed an image of lipiodol enlargement to the caudal site in the ligated group. The congestive lymph system may have impaired flow like reflux.

In the special occasion that the physiological lymphatic flow is obstructed, gallbladder carcinoma (GBC) may spread into the liver via lymphatic route. Therefore, this study was conducted to find out the direct lymphatic route draining into the liver from the gallbladder using pigs with ligated cystic ducts. After injecting the carbon particle suspension (CH40) or the contrast medium (Lipiodol) into the subserosal layer of the gallbladder, the lymphatic route into the liver was examined both macroscopically and histologically. In controls, CH40 or Lipiodol drained along the cystic duct toward the hepatoduodenal ligament. After occlusion of cystic duct, CH40 was interrupted at the ligated point, and then spread into the liver nearby the gallbladder bed, running off to the liver hilus, toward the hepatoduodenal ligament. This route was confirmed by the Lipiodol drainage into the right median lobe of the liver, equivalent to the segments V and IV a in humans. We presented for the first time the emergence of lymphatic drainage from the gallbladder into the liver after the occlusion of physiological lymphatic route using pigs. This implies that the direct spread into the segments V and IV a of liver should be considered in the surgical treatment of advanced GBC.

Overproduction of heat shock protein 70 (HSP70) in the liver protects hepatocytes under various pathologic conditions. In this study we examined the effects of a nontoxic HSP70 inducer, geranylgeranylacetone (GGA), on acute hepatic failure after 95% hepatectomy in rats. When GGA (100 mg/kg) or vehicle was intragastrically administered to rats 4 hours before 95% hepatectomy, all 25 rats pretreated with vehicle died within 60 hours after the operation, whereas 10 of 25 rats pretreated with GGA survived. During the 24-hour postoperative period, GGA significantly suppressed the release of aspartate or alanine aminotransferase and elevation of the serum interleukin-6 level, and completely inhibited an increase in the serum level of tumor necrosis factor-alpha. Histologic examinations showed that GGA prevented hemorrhagic necrosis, which was observed in vehicle-treated livers more than 12 hours after the operation. During the 24-hour postoperative period, HSP70 induction was absent in remnant livers of vehicle-treated rats. In contrast, GGA stimulated the HSP70 mRNA expression and HSP70 accumulation within 4 hours, and viable hepatocytes contained abundant HSP70 in their nuclei. Our results suggest that GGA may prevent acute liver failure after massive hepatectomy, at least in part, by enhancing HSP70 induction in the remnant liver.

Purpose The aim of this study was to establish the novel automatic method to quantify blood flow volumes of the major intracranial arteries by using SPECT. Methods We created the vascular templates to cover the territory supplied by the major intracranial arteries. Each blood flow volume was calculated as the regional cerebral blood flow on SPECT using this template × volume size of the template. In this study, we evaluated the volume flows in 22 cerebral hemispheres with normal perfusion and 28 hemispheres with severe stenosis in the internal cerebral artery (ICA) or middle cerebral artery (MCA) and that at acetazolamide test in 16 normal hemispheres and 20 hemispheres with stenosis. Results The mean blood flow volumes of the ICA and MCA in the normal hemispheres increased to more than 40% after acetazolamide test (161-228 mL/min for ICA and 111-157 mL/min for MCA), although those in the hemispheres with stenosis increased to less than 35% (158-192 mL/min for ICA and 107-127 mL/min for MCA). The receiver operating characteristic analyses revealed that the simple difference between the blood flow volume at acetazolamide test and that at rest using the new MCA template was superior to detecting reduction of cerebrovascular reactivity (CVR), compared with the conventional percent CVR using the original template. Conclusions Blood flow volumes of the intracranial arteries had been able to be quantified automatically on SPECT, and difference of CVR was available for predicting the blood demand-supply balance.

Obesity is a risk factor for the onset of liver cancer in patients with cirrhosis. To prevent overfeeding and obesity, estimation of energy requirement is important, but energy expenditure in patients with liver cirrhosis has not been fully elucidated. This study aimed to investigate resting energy expenditure (REE) and energy intake in patients with cirrhosis and determine adequate energy intake criteria. In this cross-sectional study, indirect calorimetry measurement was conducted in 488 Japanese inpatients with cirrhosis. We compared REE measured by indirect calorimetry (M-REE) with basal energy expenditure (BEE) predicted by the Harris-Benedict equation (H-BEE) and Dietary Reference Intakes (DRI) for Japanese (D-BEE). Mean M-REE (1256 kcal) was significantly lower than H-BEE (1279 kcal); however, it was not significantly different from D-BEE (1254 kcal). Mean M-REE expressed in relation to body weight (BW; REE/kg BW) was 21.7 kcal/kg BW. H-BEE was significantly higher than M-REE in patients in the first and second quartiles of BMI, and D-BEE was significantly different from MREE in patients in the highest and lowest quartiles of BMI. Average energy intake was 30.5 kcal/kg BW, which was 1.4 times greater than REE/kg BW. Although DRI is a useful tool for the estimation of REE in patients in the second and third quartiles of BMI, M-REE is recommended to ensure the provision of adequate nutritional care to patients with cirrhosis, including those in the highest and lowest quartiles of BMI.肥胖是肝硬化患者引发肝癌的一个风险因子。为了预防过量饮食和肥胖，估计能量需求是不必可少的。但是对肝硬化患者能量消耗情况尚未充分了解。本研 究旨在调查肝硬化患者的静息能量消耗(REE)以及能量摄取情况，从而制定能量 摄取的标准。本横断面研究主要对日本488 名肝硬化病人进行了间接热量测 定，并将间接热量测定法(M-REE)测得的REE 结果与Harris-Benedict 方程计算 的基础能量消耗(BEE)结果(H-BEE)以及日本膳食指南(DRI)推荐的标准(D-BEE) 进行比较。M-REE 的平均值(1256 kcal)显著低于H-BEE(1276 kcal)；但与DBEE( 1254 kcal)相比差别不大。M-REE 的均值与体重(BW; REE/kg BW)的关系为 21.7 kcal/kg BW. BMI 在第一和第二四分位数的病人的H-BEE 显著高于MREE， 而且BMI 在最高和最低四分位数病人的D-BEE 都与M-REE 有明显差 别。平均能量摄取量为30.5 kcal/kg BW，高于REE/kg BW 1.4 倍。虽然DRI 可 以用来帮助估计BMI 在第二和第三四分位数病人的REE，但M-REE 则能够保 证肝硬化病人得到足够的营养供应，即使BMI 在最高四分位数和最低四分位数 的病人也不例外。

This study was carried out to clarify the clinicopathological features of hepatocellular carcinoma (HCC) arising in patients without viral infection and to confirm the influence of metabolic syndrome (MS) on characteristics in HCC patients.Two hundred and thirty-three hepatectomized HCC patients were enrolled. The status of the hepatitis viral infection was defined; non-B non-C (NBNC) (n = 15), negative for HBs-Ag, HBc-Ab or HCV-Ab; HBV (n = 70); HCV (n = 148). We compared clinicopathological features and surgical outcomes among three groups. Additionally, fifty-six HCC patients who were evaluated on coexistence of MS were divided into two groups and analyzed; MS (n = 16) and non-MS (n = 40) groups.In NBNC-patients, preoperative platelet counts and ICGR15 were significantly better compared to HCV-patients (21.8 x 10(4)/mm3 vs. 11.3 x 10(4)/mm3, 14.0% vs. 19.2%, p0.05). Body mass index was significantly higher in NBNC-patients (24.9 vs. 22.4, p0.05). Overall survival rates were significantly higher in NBNC-patients compared with HBV or HCV-patients (5 y: 87.5% vs. 48.8%, 42.9%, p0.05). For NBNC-patients there were significantly more patients in the MS group than in the non-MS group.HCC with MS included more NBNC-HCC than HBV or HCV related HCC. Aggressive hepatectomy contributed to the favorable outcome in NBNC-patients because of their better liver function.

Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity among pancreatic neoplasms that ranges from low-grade dysplasia to invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor progression in various cancers. Moreover, Notch signaling is one of the important upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes pathological progression of IPMN.We evaluated the expression of EMT-promoting transcription factors Twist and B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) in IPMN.Patients who underwent resections at our institute and its affiliated hospital were enrolled in this study (n = 35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in resected specimens was investigated by immunohistochemistry. Expression of these proteins was compared with the clinicopathological factors and patient survival.Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs with high-grade dysplasia (P 0.05) and invasive carcinoma (P 0.05) than that in IPMNs with low-grade dysplasia. High expression of Twist was correlated with Jagged1 expression and inversely correlated with expression of E-cadherin (P = 0.06 and P 0.05, respectively). In survival analyses, the recurrence rate was significantly higher in the group that showed simultaneous high expression of Twist and Bmi1 (P 0.05).Expression of Twist and Bmi1 is associated with aggressiveness and poor prognoses of IPMN through EMT promotion that might be induced by Notch signaling.

Several risk factors for arterial calcification have been reported but controversial. The aim of this study was to clarify the interactions among chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, and dyslipidemia in altering the risk of arterial calcification in the three different arterial locations and the intramural location at the internal carotid artery (ICA) origins. Calcified burdens at the ICA origins, the aortic arch, and its orifices were evaluated in a retrospective fashion by using computed tomography angiography in 397 patients. The multivariate analyses were adjusted for age, gender, CKD, DM, hypertension, dyslipidemia, and current smoking status. Additionally, subgroup analyses in each variable were conducted. Our multivariate logistic regression analyses revealed that CKD was significantly associated with the outside-wall calcification at the ICA origins, whereas DM was only associated with the inside-ICA-wall calcification. Additionally, we found that DM increased the association between CKD and arterial calcification at the aortic arch and its orifices, and the outside-wall at the ICA origins. Hypertension was significantly associated with the calcification at the orifices of the aortic arch branches synergistically with CKD. Dyslipidemia did not have any significant association with calcification in any of the three vascular beds. CKD had the highest prevalence risk of calcification in common with the three different vascular beds. CKD in combination with DM, as well as hypertension in combination with CKD, were key relationships affecting the risk of arterial calcification, especially at the aortic arch and its orifices.