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Left-side portal hypertension (LSPH) is caused by isolated obstruction of the splenic vein and is associated with esophagogastric varices that extend from the lower esophagus to the greater curvature of the gastric body. Here, we report on a 74-year-old man with a pancreatic neuroendocrine neoplasm (NEN) in the pancreatic tail with multiple liver metastases. We decided that partial splenic embolization (PSE) was the best course of treatment to prevent rupture of the gastric varices, which were classified as markedly enlarged, nodular, or tumor-shaped and showed erosion of the mucosa. After PSE, the patient had no major complications and was discharged. At 3 and 6 months after the procedure, esophagogastroduodenoscopy and enhanced computerized tomography showed that the gastric varices had improved. This case demonstrates the usefulness of PSE for LSPH in patients with unresected pancreatic NEN.

Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency. High levels of MSI at mononucleotide and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the MMR genes, hMLH1 and hMSH2. CRC with low levels of MSI (MSI-L) exists; however, its molecular basis is unclear. There is another type of MSI—elevated microsatellite alterations at selected tetranucleotide repeats (EMAST)—where loci containing [AAAG]n or [ATAG]n repeats are unstable. EMAST is frequent in non-CRCs; however, the incidence of EMAST and its cause in CRC is not known. Here, we report that MutS homologue 3 (MSH3) knockdown or MSH3-deficient cells exhibit the EMAST phenotype and low levels of mutations at dinucleotide repeats. About 60% of 117 sporadic CRC cases exhibit EMAST. All of the cases defined as MSI-H (16 cases) exhibited high levels of EMAST. Among 101 non–MSI-H cases, all 19 cases of MSI-L and 35 of 82 cases of MSS exhibited EMAST. Although non–MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2% to 50% of the total tumor cell population, the tissues exhibiting EMAST contained more MSH3-negative cells (average, 31.5%) than did the tissues not exhibiting EMAST (8.4%). Taken together, our results support the concept that MSH3 deficiency causes EMAST or EMAST with low levels of MSI at loci with dinucleotide repeats in CRC. [Cancer Res 2008;68(20):8465–72]

Supplementary Table 1 from Genetic Instability Caused by Loss of MutS Homologue 3 in Human Colorectal Cancer

Supplementary Figures 1-2 from Genetic Instability Caused by Loss of MutS Homologue 3 in Human Colorectal Cancer

Since colorectal metastases from primary lung cancer are rare, the location of metastatic lesion and prognostic factors have not been well evaluated. Therefore, we carried out a systematic review and meta-analysis to assess the clinicopathological characteristics and prognostic factors of Japanese patients with colorectal metastasis from lung cancer. We searched the Ichushi-Web database from January 1964 to December 2020. We found 59 colorectal metastases in 52 cases for this meta-analysis. Small cell carcinoma was shown to have significantly more metastases to the appendix than non-small cell carcinoma. However, there was no significant correlation between location and histology when classified into right and left colons (P = 0.247). The median overall survival after diagnosis was 6 months. Univariate analysis showed that adenocarcinoma (Hazard Ratio (HR) 0.383, P = 0.024), simultaneous metastasis (HR 0.325, P = 0.046), and chemotherapy group (HR 0.482, P = 0.044) were good prognostic factors. Multivariate analysis confirmed that chemotherapy (HR 0.38, P = 0.02) was an independent good prognostic factor for overall survival. In conclusion, although there was no statistical difference, right colon metastases were more frequent than left colon metastases. Chemotherapy may be effective for colorectal metastases from lung cancer.

Pancreatic leiomyosarcoma (PLMS) is an extremely rare tumor that accounts for 0.1% of pancreatic malignancies, and its chemotherapy has yet to be established. Generally, soft-tissue sarcoma chemotherapy is standard treatment with doxorubicin (DXR) alone. However, the effectiveness of gemcitabine (GEM) plus docetaxel (DOC) has been shown in uterine leiomyoma. In contrast, the GEM plus nab-paclitaxel (PTX) regimen has been established as first-line chemotherapy for unresectable pancreatic cancer. For this study, we selected the GEM plus nab-PTX regimen for patients with PLMS, achieving success in approximately 10 months. From a search on PubMed, we found only 12 cases of PLMS (including this case) that underwent chemotherapy. Our case is the first reported patient to have survived more than 2 years with chemotherapy alone. In a nude mouse model, the GEM plus DOC regimen was shown to significantly decrease tumor size when compared with DXR in leiomyosarcoma, and the GEM plus nab-PTX regimen was reported to significantly reduce necrosis when compared with DXR alone, GEM alone, DOC alone, nab-PTX alone and GEM plus DOC in soft-tissue sarcoma. GEM plus nab-PTX therapy might therefore be the first choice for soft-tissue sarcoma and leiomyosarcoma. This is the first reported case of PLMS treated with GEM plus nab-PTX.

Positive margins are reported in from 4.8 to 9.5% of all gastric cancer surgeries and they have a negative impact on the overall survival. Few cases with positive duodenal margins have been included in previous studies regarding the prognosis. This multi-institutional retrospective study included 115 gastric cancer patients with positive duodenal margins following gastrectomy between January 2002 and December 2017. The association between clinicopathological factors and the overall survival was evaluated by univariate and multivariate analyses. The three-year overall survival was 22% and the median survival was 13 months. A multivariate analysis found that distant metastasis, no postoperative chemotherapy, and non-Type 4 disease were significantly associated with a poor survival. Patients without distant metastasis who received postoperative chemotherapy had a 3-year overall survival of 56% and a median survival of 44 months. The patients who underwent post-operative chemotherapy showed a significantly better OS compared with those who did not undergo post-operative chemotherapy, regardless of the existence of distant metastasis. Postoperative chemotherapy may, therefore, improve the prognosis of surgically treated gastric cancer patients with positive duodenal margins.

A 61-year-old patient with advanced gastric cancer was treated with ramucirumab plus albumin-suspended paclitaxel as second-line treatment. The treatment resulted in exposure of the right mandible around an implant. The implant was removed, and sequestration was not observed. The patient was diagnosed with oral mucosal necrosis. Thus, implants may cause mucosal necrosis due to angiogenesis inhibitors.

Background In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose–response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace. Methods Male and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3 CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days. Results CWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3 and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3 CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3 was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages. Conclusions Pulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3 CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined. Graphical Abstract

BackgroundWith the rapid development of alternative methods based on the spirit of animal welfare, the publications of animal studies evaluating endpoints such as cancer have been extremely reduced. There have been no systemic inhalation exposure studies of titanium dioxide nanoparticles (TiO2 NPs) using CByB6F1-Tg(HRAS)2Jic (rasH2) 26-week study mice model for detecting carcinogenicity.MethodsMale and female rasH2 mice were exposed to 2, 8 or 32 mg/m3 of TiO2 NPs for 6 hours/day, 5 days/week for 26 weeks using a whole-body inhalation exposure system, with reference to the Organization for Economic Co-operation and Development principles of Good Laboratory Practice. All tissues including lungs, and blood were collected and subjected to biological and histopathological analyses. Additionally, Ki67 positive index were evaluated in mice lung alveolar epithelial type 2 cell (AEC2).ResultsThis study established a stable method for generating and exposing TiO2 NPs aerosol, and clarified the dose-response relationship by TiO2 NPs inhalation to rasH2 mice. TiO2 NPs exposure induced deposition of particles in lungs and mediastinal lymph nodes in a dose-dependent manner in each exposure group. Additionally, alveolar inflammation was only observed in 32 mg/m3 exposure group in both the sexes. Exposure to TiO2 NPs, as well as other organs, did not increase the incidence of lung tumors in any group, and pulmonary fibrosis and pre-neoplastic lesions were not observed in all groups. Finally, the cell proliferative activity of AEC2 was examined, and it was not increased by exposure to TiO2 NPs.ConclusionsThis is the first report showing the lack of pulmonary fibrogenicity and carcinogenicity (no evidence of carcinogenic activity) of TiO2 NPs in 26-week inhalation study in rasH2 mice exposed up to 32 mg/m3, which is considered to be a high concentration. Macrophages undergoing phagocytosis due to TiO2 NPs exposure formed inflammatory foci in the alveolar regions of exposed mice but did not develop fibrosis or hyperplasia or tumors. Moreover, the cell proliferative ability of AEC2 in lesions was not increased. In addition, no carcinogenicity was observed for any organs other than the lungs in this study.

BackgroundRecently in Japan, six workers at a chemical plant that manufactures resins developed interstitial lung diseases after being involved in loading and packing cross-linked water-soluble acrylic acid polymers (CWAAPs). Since CWAAPs are not on the list of occupational diseases, the present study examined the lung damage potential of two CWAAPs (CWAAP-A and CWAAP-B) in rats, investigated pathological mechanisms, and established a method to rapidly evaluate the harmfulness of CWAAPs.MethodsUsing a whole-body inhalation exposure system, male F344 rats were exposed once to 40 or 100 mg/m3 of CWAAP-A for 4 hours or to 15 or 40 mg/m3 of CWAAP-A for 4 hours per day once per week for 2 months (a total of 9 exposures). In a separate set of experiments, male F344 rats were administered 1 mg/kg CWAAP-A or CWAAP-B by intratracheal instillation once every two weeks for 2 months (a total of five doses). Lung tissues, mediastinal lymph nodes, and bronchoalveolar lavage fluid were collected and subjected to biological and histopathological analyses.ResultsA single 4-hour exposure to CWAAP caused alveolar injury, and repeated exposures resulted in regenerative changes in the alveolar epithelium with activation of TGFβ signaling. During the recovery period after the last exposure, some alveolar lesions were partially healed, but other lesions developed into alveolitis with fibrous thickening of the alveolar septum. Rats administered CWAAP-A by intratracheal instillation developed qualitatively similar pulmonary pathology as rats exposed to CWAAP-A by inhalation. At 2 weeks after intratracheal instillation, rats administered CWAAP-B appeared to have a slightly higher degree of lung lesions compared to rats administered CWAAP-A, however, there was no difference in these lesions of CWAAP-A and CWAAP-B in rats examined 18 weeks after administration of these materials.ConclusionsThe present study provides evidence of rat lung pathogenesis after inhalation exposure to CWAAP-A. This study also demonstrates that the lung pathology of rats exposed to CWAAP-A by systemic inhalation was qualitatively similar to that of rats administered CWAAP-A by intratracheal instillation. The use of intratracheal instillation as an adjunct to systemic inhalation is expected to significantly accelerate the risk assessment for a variety of CWAAPs.

Aim This study aimed to compare the efficacy of taxane-based and platinum-based regimens in patients with early recurrent gastric cancer after radical surgery with S-1 adjuvant chemotherapy. Methods The medical records of 118 patients from six institutes with early recurrent stage II/III gastric cancer, who developed recurrence during adjuvant S-1 or within 6 months after completion of adjuvant therapy between January 2006 and December 2017, were retrospectively analyzed. Patients treated with second line chemotherapy were enrolled and followed to the end of December 2019. The impact of two regimens, taxane-based (n = 46) versus platinum-based (n = 31), on treatment outcome were evaluated using multivariate analysis. Results Median overall survival was 9.0 months and median progression-free survival was 4.1 months. No difference was observed in overall survival between taxane-based and platinum-based regimens (P = 0.64). Although not significant, the response rate of platinum-based regimens was better than that of taxane-based regimens (16% vs. 6.5%, P = 0.26). Multivariate analysis identified performance status (P = 0.040), multiorgan metastases (P = 0.029), and undifferentiated histological type (P = 0.018) as independent poor prognostic factors. In undifferentiated histological type, multiorgan metastases (P = 0.013) and taxane-based regimens (P = 0.018) were independent prognosis factors characterized by multivariate analysis. Conversion rate to third-line chemotherapy or more was 51% in undifferentiated histological type and 65% in differentiated histological type (P = 0.26). Conclusion Platinum-based regimens may be recommended for undifferentiated early recurrent gastric cancer after S-1 adjuvant chemotherapy.

ORIGINAL ARTICLE, Background: The relationship of thymidine phosphorylase (TP) expression and patient outcomes has been investigated in various cancers. This study investigated the association of TP expression, serum TP, and platelet counts in patients with gastric cancer. Methods: A series of 77 patients with gastric adenocarcinoma were enrolled in the study. Pretreatment serum TP was determined by enzyme-linked immunosorbent assay and the patient characteristics, including platelet count, gender, age, tumor stage and histological grade, and immunoreactivity of surgically resected tissue specimens, were recorded. Results: The serum TP level was significantly higher in poorly differentiated and signet ring cell adenocarcinomas than in more differentiated types. TP expression was observed within well- and moderately differentiated adenocarcinoma cancer cells, but was significantly weaker in poorly differentiated adenocarcinomas and signet ring cell carcinomas. There were no significant differences in the survival of patients with different histological types and serum TP levels. Although the differences were not statistically significant, high TP expression and high platelet counts were poor prognostic factors. TP expression was not correlated with serum TP levels, but was slightly correlated with the platelet count. Conclusions: TP expression in gastric cancer tissue was slightly related to the platelet count rather than to the serum TP concentration. Therefore, a larger number of patients should be evaluated to assess the relationship between platelet count and capecitabine treatment response in gastric cancer patients.

Purpose To compare contrast-enhanced ultrasonography (CEUS) using Sonazoid with Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in the diagnosis of liver metastases in patients with colorectal cancer. Methods A total of 69 patients diagnosed with or suspected of having liver metastasis were enrolled. These hepatic lesions were diagnosed by histopathological examination after surgical resection or based on follow-up using various imaging modalities. The diagnostic accuracies of CEUS and EOB-MRI were compared. Results One hundred thirty-three lesions were detected. Of these lesions, 109 were diagnosed as liver metastases. Of the 133 lesions, 90.2% were detected on CEUS, and 98.5% on EOB-MRI. One hundred nine lesions were diagnosed as liver metastasis. The areas under the receiver operating characteristic curve for diagnosis were 0.906 and 0.851 on CEUS and EOB-MRI, respectively (p = 0.41). Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and overall accuracy were 90.8%, 84.5%, 97.1%, 67.1%, and 90.2%, respectively, for CEUS, and 95.4%, 70.8%, 93.7%, 77.3%, and 91%, respectively, for EOB-MRI. Conclusions CEUS has a higher specificity and PPV for the diagnosis of liver metastasis than EOB-MRI. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:138–144, 2017

Esophageal neuroendocrine cell carcinoma (NEC) is extremely rare, and its treatment strategy has not been established. Systematic review and meta-analysis were carried out to assess the treatment and prognosis of patients with esophageal NEC in Japan. The Ichushi-Web database was searched from January 1964 to May 2018. In total, 141 cases of esophageal NEC were included in the analysis. The survival of the chemotherapy group with stage II/III esophageal NEC was better than that of the surgery group. Meanwhile, the survival of the adjuvant treatment group with stage II/III esophageal NEC was significantly better than that of the surgery alone group. In patients with stage IV esophageal NEC, no significant differences were observed in terms of treatment response from the three regimens: irinotecan/platinum and etoposide/platinum compared with 5-fluorouracil/platinum. Moreover, no significant differences were observed in the survival of patients who received the chemotherapy regimens. However, the 2-year survival rates of the irinotecan/platinum (26%) group and etoposide/platinum (27%) group were higher than that of the 5-fluorouracil/platinum (0%) group. In esophageal NEC, chemotherapy may be used as the first-line treatment. Irinotecan/platinum or etoposide/platinum can be the first-line regimen for chemotherapy. However, the additive effects of surgery remain unclear.

Background Although bevacizumab plus FOLFOX is a standard treatment for metastatic colorectal cancer, oxaliplatin must be withdrawn in many patients because of cumulative neurotoxicity. We postulated that a reduced dose of oxaliplatin and modified treatment schedule would prolong the time to treatment failure and evaluated bevacizumab combined with a modified OPTIMOX1 regimen (mOPTIMOX1, oxaliplatin dose: 85 mg/m2). Methods Eligible patients had a histologically confirmed diagnosis of metastatic colorectal cancer and a performance status of 0–1. Patients were excluded if they had grade 1 or higher peripheral sensory neuropathy or had previously received chemotherapy for metastatic colorectal cancer. Patients received bevacizumab plus mFOLFOX6 every 2 weeks for 6 cycles, followed by 12 cycles of a simplified biweekly regimen of leucovorin and fluorouracil (sLV5FU2) plus bevacizumab. Oxaliplatin was then reintroduced, and bevacizumab plus mFOLFOX6 was continued until progressive disease. Results The median duration of disease control was 11.7 months (95 % confidence interval [CI], 9.7–13.5 months). The median overall survival was 23.1 months (95 % CI, 18.8–27.9 months). The overall response rate according to both the RECIST and WHO criteria was 51.3 %. The most common grade 3 or 4 toxicities were neutropaenia (32.5 %), hypertension (17.5 %), leukocytopaenia, sensory neuropathy, and diarrhoea (10.0 %). There were no treatment-related deaths. Conclusions Bevacizumab plus mFOLFOX6 was well tolerated, and patients could continue chemotherapy for longer than with conventional FOLFOX regimens. This regimen might be an effective treatment option for patients with metastatic colorectal cancer.

Primary hepatic marginal zone B-cell malignant lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is extremely rare. We present a case in which a lesion was diagnosed as 2 contiguous tumors (MALT lymphoma and hemangioma) using contrast-enhanced ultrasonography (US) with sonazoid. There has been no previous case of contiguous hepatic MALT lymphoma and hemangioma. The present case was a female with no medical history. We detected a snowman-like appearance, which was a tumor of 15 mm in diameter with hypo- and hyper-echogenicities in the lateral and medial parts, respectively, in the Couinaud's segment (S6) of the liver on US. The tumor appeared as a single lesion with a low-density area in the unenhanced phase and prolonged enhancement in the equilibrium phases on dynamic CT. On MRI, the whole lesion showed a low-intensity signal on T1-weighted imaging, but isointensity in the lateral part and high intensity in the medial part were seen on T2-weighted imaging. On contrast-enhanced US, the lateral hypoechoic region was homogenously hyperenhanced in the early vascular phase, and the contrast medium was washed out after about 30 s; in contrast, the medial hyperechoic region was gradually stained from the margin toward the central region. The tumor showed a defect in both hypo- and hyperechoic regions in the postvascular phase. Hemangioma was suspected for the medial part based on the typical image findings, but the lateral part was not given a diagnosis. Thus, surgical resection was performed. The medial part was a hemangioma, and the lateral part was a MALT lymphoma by histopathological findings.

The recurrence of gastric cancer is rarely associated with cardiac tamponade induced by carcinomatous pericarditis. We encountered a patient in whom cancer recurred as carcinomatous pericarditis 9 years after surgery for advanced gastric cancer. Furthermore, pericardial effusion caused marked subcutaneous edema in her trunk and lower limbs after percutaneous pericardial drainage was applied to treat cardiac tamponade. A 49-year-old woman presented with lower limb edema and exertional dyspnea 9 years after distal gastrectomy for advanced gastric cancer. Chest computed tomography and ultrasonography showed bilateral pleural effusion and pericardial effusion. Pericardial drainage and thoracocentesis were performed, and her symptoms of respiratory distress remitted. Class V adenocarcinoma was detected on cytology from both effusions, and was diagnosed as the recurrence of gastric cancer. After systemic chemotherapy, she was admitted for the aggravation of dyspnea because of recurrent retention of pericardial effusion. Pericardiocentesis was repeated. The pericardial effusion became subcutaneously retained in the trunk below the puncture site over the lower limbs via the drainage route. Edema in the trunk below the abdomen and lower limbs gradually aggravated over time. The skin extended and became sclerotic because of severe edema, liquid leaked from abdominal skin injuries, and the condition became similar to skin lymphorrhea in lymphedema. Neoplastic cardiac tamponade due to gastric cancer has an extremely low incidence and a poor prognosis. We encountered a patient in whom pericardial effusion caused subcutaneous edema in the trunk and lower limbs after percutaneous pericardial drainage was applied to treat carcinomatous pericarditis associated with gastric cancer.

Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized benign vascular lesion of the spleen. Detection of SANT as an incidentaloma has increased due to improvements in imaging techniques. However, a definitive diagnosis of SANT on CT or MRI remains difficult. We report the use of contrast-enhanced ultrasonography with Sonazoid in a case of SANT in a 50-year-old woman, with gross and microscopic pathologic correlations.

We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival.

We aimed to determine the usefulness of arrival time parametric imaging (AtPI) using contrast-enhanced ultrasonography (CEUS)with Sonazoid in the evaluation of early response to sorafenib for hepatocellular carcinoma (HCC). Thirteen ad- vanced HCC patients with low a / -fetoprotein (AFP) level (≤35 ng/mL) who received sorafenib for at least 4 weeks were enrolled in this study. CEUS was performed before and after treatment (2 weeks), and the images of the target lesion in the arterial phase were analyzed by AtPI. In the color mapping images obtained by AtPI, the mean arrival time of the contrast agent in the target lesion from the starting point (mean time: MT) was calculated. In each patient, differences between MT before and MT 2 weeks after treatment were compared. MT (+) and MT(-) groups were designated as such if the difference was 0 or greater(blood flow velocity of the lesion was reduced)and less than 0 sec(blood flow velocity of the lesion was increased), respectively. The overall survival was evaluated between the 2 groups. In the MT (+) group (7 patients) and MT (-) group (6 patients), the median survival times were 307 and 208 days, respectively, which was statistically significant. We suggest AtPI is useful for evaluating early response to sorafenib in advanced HCC patients with low AFP level.

Purpose To compare contrast‐enhanced ultrasonography (CEUS) using Sonazoid with Gd‐EOB‐DTPA‐enhanced MRI (EOB‐MRI) in the diagnosis of liver metastases in patients with colorectal cancer. Methods A total of 69 patients diagnosed with or suspected of having liver metastasis were enrolled. These hepatic lesions were diagnosed by histopathological examination after surgical resection or based on follow‐up using various imaging modalities. The diagnostic accuracies of CEUS and EOB‐MRI were compared. Results One hundred thirty‐three lesions were detected. Of these lesions, 109 were diagnosed as liver metastases. Of the 133 lesions, 90.2% were detected on CEUS, and 98.5% on EOB‐MRI. One hundred nine lesions were diagnosed as liver metastasis. The areas under the receiver operating characteristic curve for diagnosis were 0.906 and 0.851 on CEUS and EOB‐MRI, respectively (p = 0.41). Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and overall accuracy were 90.8%, 84.5%, 97.1%, 67.1%, and 90.2%, respectively, for CEUS, and 95.4%, 70.8%, 93.7%, 77.3%, and 91%, respectively, for EOB‐MRI. Conclusions CEUS has a higher specificity and PPV for the diagnosis of liver metastasis than EOB‐MRI. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:138–144, 2017

The bile duct of Luschka (BDL) is an anatomic anomaly that is an important cause of bile leakage after bile duct surgery. We report a case of bile duct carcinoma with dilated BDL that was diagnosed by ultrasonography (US). An 83-year-old man presented with an obstructive jaundice. US on admission revealed the presence of a solid hypoechoic mass in the bile duct at the hepatic duct confluence and a branch of the bile duct, about 2-4 mm in diameter, distinct from the dilated right anterior hepatic duct slightly upstream of the tumor. This branch had a spiral structure, extended along the gallbladder bed on the surface of segment 5 (S5) of the liver, and emanated small branches that entered the hepatic parenchyma. There has been no previous report of delineation of BDL by preoperative US.

Heterotopic pancreas (HP) is typically an asymptomatic malformation that can present anywhere along the gastrointestinal tract. It is often detected incidentally on surgery for other diseases or autopsy. We encountered 2 patients with jejunal HP incidentally detected by computed tomography (CT) performed for close evaluation of other diseases. In a 57-year-old woman diagnosed with reactive lymphoid hyperplasia on the dorsal portion of the pancreas head, CT detected a 15 mm oval-shaped submucosal lesion at the jejunum. In an 87-year-old woman diagnosed with type 2 adenocarcinoma occupying the sigmoid colon, CT detected a round-shaped submucosal tumor 15 mm in diameter in the jejunum. Both cases were histologically diagnosed as type 1 HP according to the classification by Heinrich. Contrast-enhanced CT revealed that the CT analyses of HP and pancreatic parenchyma were nearly identical in the arterial phase, but in the equilibrium phase, contrast enhancement persisted longer in HP than in the pancreatic parenchyma. There has been no report of asymptomatic jejunal HP preoperatively diagnosed by CT. These cases are presented with a review of the literature, particularly focusing on CT findings.

Aim: In this study, the aim was to determine the demographic characteristics of elderly patients with gastroduodenal ulcer who had undergone endoscopic hemostasis by comparing them with younger patients. Methods: A total of 353 patients with Forrest class I–IIa hemorrhagic gastroduodenal ulcer who underwent endoscopic hemostasis at our hospital between December 2004 and May 2010 were divided into two groups: one for those 75 years or older (old-old group; n = 71; age ≥75 years) and one for those younger than 75 years (younger group; n = 282; age

症例は80歳女性．切除不能膵癌に対して胆管ステント留置後に化学療法が施行されていた．第441病日に嘔吐のため入院した．上部消化管造影検査と内視鏡検査にて膵癌十二指腸浸潤による十二指腸閉塞と診断した．外科的手術に同意を得られず第457病日に十二指腸ステント留置術が行われた．早期閉塞のため第464病日に追加ステント留置を施行した．低残渣食摂取可能となったが，胆管炎併発したため，第485病日に経皮胆道ドレナージチューブを留置し退院した．第519病日にステント再閉塞のため再入院した．第535病日に追加十二指腸ステントを留置した．その際偶発症なく，水分摂取可能となったが，初診から第553病日に原病死した．末期膵癌患者十二指腸閉塞に対しても複数本の十二指腸ステント留置することによって，一時的に経口摂取が可能となった．患者のQOLに寄与でき，有用と考えられた．

症例は36歳男性．2009年12月に排便困難，下血を主訴に近医を受診し，精査にてS状結腸癌の診断となり当科紹介入院となった．大腸内視鏡検査でS状結腸に内視鏡通過不能な全周性の腫瘍を認め，生検で低分化腺癌と診断された．CT検査所見にて，腫瘍は骨盤内を大きく占有し，膀胱への浸潤とリンパ節の腫大を認め（cT4N2），切除困難が予想された．患者よりIC取得後，術前mFOLFOX6導入し，4コース終了後に根治術を施行した．病理組織学的所見では，原発巣は線維化のみで癌細胞はなく（grade 3），リンパ節転移，膀胱壁への浸潤も認めず，病理学的完全奏功（CR）と診断した．局所進行大腸癌に対する術前mFOLFOX6療法の妥当性は未だ確立されていないが，手術治療の根治性を高める上で有用と考えられた．

This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer. Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25–60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses. Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7–37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes. The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

We compared the benefits of sorafenib with that of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (ad-HCC) refractory to transcatheter arterial chemoembolization (TACE). We evaluated the patient characteristics, the median survival time (MST), and the prognostic factors in 17 patients in the sorafenib group and in 26 patients in the HAIC group. No significant difference was observed in the patient characteristics between the groups. The MST in the sorafenib group and HAIC group was 483 days and 284 days, respectively. A significantly longer survival time was noted in the sorafenib group (p=0.033). The prognostic factors were sorafenib therapy in all 43 patients(hazard ratio: 3.32 [95% CI: 1.36-8.10], p=0.008) and the longer treatment period of sorafenib in the sorafenib group(hazard ratio: 0.99 [95% CI: 0.984- 0.999], p=0.009). When compared with HAIC, sorafenib showed favorable treatment results in patients with ad-HCC refractory to TACE.

This prospective non-randomized controlled trial aimed to compare the efficacy of sorafenib vs hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma.Forty-seven patients treated with sorafenib (sorafenib group) and 77 patients treated with HAIC (HAIC group) were investigated retrospectively using propensity score matching (PSM) to minimize selection bias. The cumulative survival rate was investigated before and after PSM in each of the sorafenib and HAIC groups. The cumulative survival rate was compared between the sorafenib and HAIC groups, and among the TNM stage by the Liver Cancer Study Group of Japan (LCSGJ TNM stage).No significant difference was noted in overall survival (OS) between the sorafenib and HAIC groups regardless of before or after PSM. On comparison of the cumulative survival rate between the groups by the same LCSGJ TNM stage, significant prolongation of OS was noted in stage IVB only in the sorafenib group (p = 0.032) after PSM.It may be better to actively introduce sorafenib for stage IVB, i.e., patients with extrahepatic metastasis.

Objectives Because bacteria represent the sole source of gut hydrogen (H 2 ) and methane (CH 4 ), fasting breath H 2 and CH 4 gases have been used as markers of colonic fermentation. The presence of carbohydrates in the colonic lumen inhibits gastric and pancreatic secretions, and also influences lower oesophageal sphincter function in gastro-oesophageal reflux disease. Materials and methods Studies were performed in 793 consecutive patients undergoing oesophagogastroscopy (270 men and 523 women, aged 19-85 years). A fasting breath sample (20 ml) was collected before endoscopy. At endoscopy, we intubated the stomach without inflation by air, and 20 ml of intragastric gas was collected through the biopsy channel. Next, the tip of the endoscope was inserted into the second portion of the duodenum without inflation by air, and 20 ml of intraduodenal gas was collected. H 2 and CH 4 concentrations of each sample were measured by gas chromatography. Results Reflux oesophagitis was found in 147 of the 793 patients. The mean values of the H 2 and/or CH 4 levels of samples taken from the stomach, duodenum and exhaled air were higher in patients with reflux oesophagitis than those without reflux oesophagitis. High H 2 and/or CH 4 levels were more frequently found in patients with reflux oesophagitis. Conclusions We concluded that the presence of fermentation in the digestive tract was considered to be a risk factor for developing reflux oesophagitis.

Background and aim A late rise in (13)CO2 excretion in the (13)C-urea breath test (UBT) should be found when the substrate passes rapidly through the stomach and makes contact with the colonic bacteria. The aim of this study was to evaluate the influence of intestinal urease activity on the results of the UBT. Method A total of 143 subjects who were diagnosed as Helicobacter pylori negative by serology, histology and rapid urease test were recruited. At the end of endoscopy, the tip of the endoscope was placed to the second part of the duodenum and 20 mL of water containing 100 mg of (13)C-urea was sprayed into the duodenum. Breath samples were taken at baseline and at 5, 10, 20, 30 and 60 min after administration. Results Of 143 subjects, breath Delta(13)CO2 values higher than 2.5 per thousand were detected in six (4.2%), four (2.8%) and five (3.5%) subjects at 20, 30 and 60 min, respectively. There was no subject with high Delta(13)CO2 values at 5 and 10 min. Only one subject had an immediate rise at 60 min. Conclusion Variability derived from urease activity in the intestinal tract appears to be minimal up to 60 min after ingestion of the test urea.

Recently, low noise gears without lubrication are required for business machines and robots, because they are used in open space. The present article provides a new type gear consisting of steel and resin (called Delrin-100), which has good lubrication characteristics. Our gear has profile shifted steel gear teeth. Delrin-100 resin is inserted in a grove, which is cut around the gear teeth of the steel gear so as to have strong gear teeth. Hence, the tooth made of Delrin resin is supported at both sides. This means that only resin gear tooth contacts to the follower gear tooth, but steel gear tooth does not contact. Production processes are presented for the gear, and its characteristics are investigated. It is ascertained that the strength of our gear is greater than that of a plastic gear, and noise of our gear is small in comparison with plastic gears. The design method is presented, and effects of frictions on the position control are also investigated.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated mortality worldwide. No effective treatment has been established for unresectable advanced HCC, and the prognosis is poor. Sorafenib is an oral multi-targeted tyrosine kinase inhibitor for unresectable advanced HCC that significantly improves progression-free and overall survival. However, in the two large phase III clinical trials (the SHARP and Asia-Pacific trials), no cases of complete response (CR) were reported. The present study reports the case of a 68-year-old male with hepatitis C virus-related cirrhosis and multiple recurrent HCCs, with a tumor thrombus of the third portal vein following resection. The patient received 400 mg once daily (half the standard dose) of sorafenib for two years and achieved a CR. At the most recent follow-up examination at one year after the cessation of treatment, the patient was observed to be in remission without clinical or imaging evidence of disease recurrence.

The importance of atrophic gastritis with intestinal metaplasia is related to the fact that it increases the risk of gastric cancer development. The aim of this study is to evaluate the diagnostic potential of serum pepsinogens in predicting the topography of intestinal metaplasia. Both dye endoscopy and 13C-urea breath test were carried out in 878 subjects. Serum pepsinogen I, pepsinogen II, and IgG antibody to Helicobacter pylori were measured. The overall prevalence of intestinal metaplasia was higher in subjects with lower PG I/II ratios and lower PG I values. Based on ROC curves, a cutoff value for pepsinogen I/II ratio of less than 3.0 would have identified intestinal metaplasia with a sensitivity of 71.7% and a specificity of 66.7% in Helicobacter pylori-positive subjects. It is possible that serum pepsinogens could be used as a screening test for high-risk subjects with intestinal metaplasia.

Objective Although the diagnostic utility of serum IgG antibodies to Helicobacter pylori (H. pylori) is well established, the usefulness of IgA-based tests is less well documented. The aim of this study was to evaluate two commercially available ELISAs, both for IgG and IgA. Patients and Methods Rapid urease test and histology analysis were performed in 183 patients. A patient was considered to be H. pylori-positive when either biopsy test was positive, and considered to be noninfected when both tests were negative. Intestinal metaplasia was determined by dye endoscopy with methylene blue. ELISA testing was performed using the EPI HM-CAP IgG and PP-CAP IgA assays and EIAgen IgG and IgA assays. Results Sensitivity was 94.7, 93.9, 94.8, and 97.0% for HM-CAP IgG, PP-CAP IgA, EIAgen IgG, and EIAgen IgA, respectively. Although sensitivity was excellent for both IgG and IgA antibodies, specificity of both IgA EIAs was low (PP-CAP 72.6%, EIAgen H. pylori IgA 59.2%). Three of 101 H. pylori-infected patients were PP-CAP positive and HM-CAP negative and four were EIAgen H. pylori IgA positive and EIAgen IgG negative. Of eight noninfected patients in whom intestinal metaplasia was found, PP-CAP IgA results were positive in three of five patients with a HM-CAP IgG negative result and EIAgen IgA was detected in one of four patients with an EIAgen IgG negative result. Conclusions Since some patients have IgA positive but IgG negative results, great care should be taken not to underestimate the prevalence of H. pylori infection from the results of IgG serology.

Background Breath hydrogen levels after ingestion of polyethylene glycol were evaluated as a method of predicting the quality of colonic preparation. Methods : One hundred patients undergoing nonemergency colonoscopy were recruited for this study. After fasting overnight, they were instructed to ingest a polyethylene, glycol solution containing 12 g lactulose at a rate of 50 mL every 5 minutes for 2 hours. During ingestion of the polyethylene glycol solution, breath samples were taken at 15-minute intervals for 240 minutes and breath hydrogen concentration was measured. Results : The preparation for colonoscopy was judged to be poor in 18% and adequate in 82%. The breath hydrogen levels over 90 minutes were significantly higher in the poor group than in the adequate group. In all patients with a breath hydrogen level less than 10 parts per million at 240 minutes, the preparation was adequate. Conversely, all patients with a poor preparation had a breath hydrogen level of more than 10 ppm at 240 minutes. Conclusions : The hydrogen breath test effectively predicts adequacy of colonic preparation.

The present study aimed to determine the usefulness of contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating the therapeutic response to sorafenib for hepatocellular carcinoma (HCC). In total, 26 patients with advanced HCC who received sorafenib and were followed up by CEUS were enrolled in the present study. CEUS was performed prior to and within 2-4 weeks of treatment, and the images of the target lesion in the post-vascular phase with a re-injection method were analyzed. The presence (+) or absence (-) of intratumoral necrosis and the intratumoral vascular architecture on micro-flow imaging (MFI) were compared prior to and subsequent to treatment. Target lesions that exhibited non-enhancement after re-injection were considered to indicate intratumoral necrosis. The intratumoral vascular architecture was classified into three groups, as follows: Vd, the intratumoral vessels visually narrowed or decreased; Vnc, the vessels remained unchanged; and Vi, the vessels were thickened or increased. Survival curves were estimated using the Kaplan-Meier method and compared using the log rank test between the intratumoral necrosis (+) and (-) groups, and among the Vd, Vnc and Vi groups. P