Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY.

BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.

Comparison of thrombocytopenia between patients with non-alcoholic fatty liver disease and those with hepatitis C virus-related chronic liver disease.

AIM: Thrombocytopenia is widely recognized as a simple surrogate marker of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Thrombocytopenia of NAFLD has not been compared with that of hepatitis C virus-related chronic liver disease (CLD-C). Here, we examined whether there is any difference in the platelet counts between patients with NAFLD and CLD-C and investigated the underlying mechanisms. METHODS: A total of 760 biopsy-confirmed NAFLD and 1171 CLD-C patients were enrolled. After stratification according to the liver fibrosis stage, platelet counts between NAFLD and CLD-C patients were compared. The platelet count, spleen size, serum albumin level, serum thrombopoietin level, and immature platelet fraction (IPF) value were also compared after covariate adjustment using propensity score (PS) matching. RESULTS: The median platelet counts (×104 /µL) of NAFLD and CLD-C patients were 20.2 and 18.7 (p = 2.4 × 10-5 ) in F1; 20.0 and 14.5 (p = 2.1 × 10-12 ) in F2; 16.9 and 12.3 (p = 8.1 × 10-10 ) in F3; and 11.1 and 8.1 (p = 0.02) in F4, respectively. In the F3 group, NAFLD patients had a significantly higher platelet count and significantly smaller spleen volume than CLD-C patients. Although the serum thrombopoietin levels were comparable between NAFLD and CLD-C patients, the IPF value of NAFLD patients was significantly higher than that of CLD-C patients. CONCLUSIONS: NAFLD patients had a significantly higher platelet count than CLD-C patients following stratification according to the liver fibrosis stage. The milder hypersplenism and higher platelet production in NAFLD than CLD-C may have contributed to this difference.

Garcin Syndrome Due to Meningeal Carcinomatosis from Gastric Cancer.

A 58-year-old woman presented to our hospital with complaints of dysphagia. Esophagogastroduodenoscopy showed an esophagogastric junction tumor with multiple duodenal intramural metastases, and computed tomography showed peritoneal metastasis. In the middle of her fourth cycle of chemotherapy, she displayed symptoms of a left-sided multi-cranial nerve palsy. She was diagnosed with Garcin syndrome caused by meningeal carcinomatosis from gastric cancer based on the results of gadolinium-enhanced brain magnetic resonance imaging and cytology of the cerebrospinal fluid. It is important not to overlook meningeal irritation symptoms or paralysis of cranial nerves and to consider the possibility of Garcin syndrome caused by meningeal carcinomatosis.

Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. METHODS: We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. RESULTS: The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. CONCLUSIONS: GMA shows effectiveness in inducing remission in UC patients not receiving steroid.

Safety and effectiveness of granulocyte and monocyte adsorptive apheresis in patients with inflammatory bowel disease in special situations: a multicentre cohort study.

BACKGROUND: The available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations. METHODS: This study included patients with ulcerative colitis (UC) or Crohn's disease who had at least one special situation feature and who had received GMA between November 2013 and March 2017. The incidence of adverse events (AEs) was compared in relation to the special situation, and patient background factors related to an AE were identified. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2. RESULTS: A total of 437 patients were included in this study. The incidence of AEs among the elderly patients (11.2%) was similar in all patients (11.4%), whereas the incidences of AEs in patients on multiple immunosuppressant medications (15.2%), patients with anaemia (18.1%) and paediatric/adolescent patients (18.9%) were higher than that in all patients (11.4%). In multivariate analysis, anaemia and concomitant immunosuppressant medications were independently associated with the incidence of AEs. Clinical remission was achieved in 46.4% of the patients with UC. CONCLUSIONS: The incidence of AEs in the elderly patients was not higher than that in all patients, whereas the incidence of AE was higher in patients with anaemia and those on multiple immunosuppressant medications than that in all patients. GMA is a safe treatment option in elderly patients with IBD.

[The impact of direct-acting antiviral therapy on the diagnosis of hepatitis-C virus-associated hepatocellular carcinoma].

Since the introduction of direct-acting antiviral (DAA)-based combination therapies in September 2014 for patients with chronic hepatitis-C (CH-C), numerous patients have been diagnosed with hepatitis-C virus (HCV)-associated hepatocellular carcinomas (HCCs) during the screening performed prior to DAA therapy. The present study was conducted on the antiviral therapy for CH-C in two phases:i) the interferon (IFN) phase between January 2011 and August 2014 and ii) the DAA phase between September 2014 and September 2016. During the DAA phase, HCCs were detected in eight patients who were referred to our hospital for anti-HCV therapy. In contrast, HCCs were detected in only two patients during the IFN phase. The number of patients with newly detected HCC in the DAA phase (20.5%) who were referred for the anti-HCV therapy was significantly higher than that in the IFN phase (1.7%). Owing to the high efficacy and safety of the DAA therapy, the number of patients referred to our hospital for anti-HCV therapy increased from 40.5 persons/year in the IFN phase to 80.3 persons/year in the DAA phase. The average ages of patients in the DAA and IFN phases were 68 and 61 years, respectively. The increase in the number of patients with newly detected HCC referred for the anti-HCV therapy in the DAA phase could be attributed to the increase in the number of referred patients for anti-HCV therapy and the aging of these patients in the DAA phase. All the eight patients with newly detected HCC who were referred for anti-HCV therapy in the DAA phase received curative treatments. The median age, rate of liver cirrhosis, and median tumor size of the patients were 69 years, 13%, and 16mm. Therefore, the findings of this study indicate that DAA therapies not only eradicate HCV infection but also contribute to the early diagnosis of HCC by encouraging the HCV-infected patients to visit hospitals and by promoting active network between hepatologists and family physicians.

Retroperitoneal Perforation Caused by Migration of a Pancreatic Spontaneous Dislodgement Stent into Periampullary Diverticula.

An 85-year-old woman underwent endoscopic retrograde cholangiopancreatography (ERCP) for obstructive jaundice. Selective bile duct cannulation was unsuccessful because of periampullary diverticula (PAD). A pancreatic spontaneous dislodgement stent (PSDS) (5F diameter, 3 cm, straight type) was inserted to prevent post-ERCP pancreatitis. Three days after ERCP, she complained of abdominal pain, and computed tomography revealed retroperitoneal perforation because of PSDS migration to the PAD. If the papillary orifice is observed at the diverticular rim or in the diverticula, a pigtailed PSDS on the duodenal side or flanged stent on the pancreatic ductal side should be inserted in order to prevent this rare adverse event.

Classification of patients with non-alcoholic fatty liver disease using rapid immunoassay of serum type IV collagen compared with liver histology and other fibrosis markers.

AIM: Non-alcoholic fatty liver disease (NAFLD) can progress to non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH). We investigated the association among serum type IV collagen level, liver histology, and other fibrosis markers in NAFLD progression. METHODS: We evaluated 184 patients diagnosed with NAFLD following biopsy, including 89 males and 95 females with an average age of 52.6 and 62.6 years, respectively. Non-alcoholic fatty liver disease was classified as NAFL or NASH using Matteoni's classification, and the grade and stage of NASH were assessed using Brunt's classification. Serum type IV collagen was measured by a rapid and sensitive latex particle-enhanced turbidimetric immunoassay. RESULTS: Forty-two patients with NAFL and 142 patients with NASH were included in this study. Compared with patients with NAFL, patients with NASH showed more significant liver function disorder and increased expression of fibrosis markers including type IV collagen, collagen 7S, Mac2-binding protein (M2BP), and hyaluronic acid (HA). Expression of type IV collagen and collagen 7S, but not M2BP and HA, was more significantly elevated in patients with stage 1 NASH than in patients with NAFL, indicating that type IV collagen and collagen 7S may be better discriminators of NASH and NAFL than M2BP and HA at an early stage of fibrosis. When patients were stratified by NAFLD activity score, type IV collagen and collagen 7S were significantly elevated as NAFLD activity score progressed, whereas M2BP and HA expression were not significantly elevated. CONCLUSION: Type IV collagen may be a useful measure of NASH severity as latex particle-enhanced turbidimetric immunoassay-based rapid type IV collagen assay can be carried out routinely.

[A case of HER2-positive and AFP-producing gastric cancer successfully treated by trastuzumab/docetaxel/S-1 combination therapy].

A 74-year-old man was referred to our hospital because of abdominal distension. Upper gastrointestinal endoscopy revealed advanced gastric cancer and early gastric cancer. HER2-positive and AFP-producing gastric cancer with peritonitis carcinomatosa showing no indication for operation was diagnosed by histopathological and radiological examinations. He was treated with trastuzumab, docetaxel, and S-1 combination chemotherapy. At the end of the second course of therapy, the primary lesion was remarkably decreased in size and was associated with a significant decrease in serum AFP level. No serious adverse events occurred except for grade 3-4 leukopenia and neutropenia. We carried out eight courses of chemotherapy. Trastuzumab, docetaxel, and S-1 combination chemotherapy promise to be one of the effective treatments for HER2-positive and AFP-producing gastric cancer that have no indication for radical cure excision.

[Case of ulcerative colitis associated with drug-induced hypersensitivity syndrome (DIHS) by salazosulfapyridine].

We experienced a case of drug-induced hypersensitivity syndrome (DIHS) for salazosulfapyridine (SASP). After we started administration of SASP in a 26-year old man with ulcerative colitis (UC), he had symptoms resembling infectious mononucleosis, high fever, skin eruption, cervical lymphadenopathy, elevate white blood cell count with atypical lymphocyte, and liver dysfunction. We diagnosed the illness as drug-induced hypersensitivity syndrome (DIHS) due to SASP. We halted SASP and started administration of methylprednisolone and prednisolone but his condition deteriorated. We changed to administration of betamethasone and he recovered. In cases of DIHS accompanied by UC, we should administer drugs carefully and recognize serious complications.

Evaluation of transcatheter arterial embolization therapy on hepatocellular carcinomas using contrast-enhanced harmonic power Doppler sonography: comparison with CT, power Doppler sonography, and dynamic MRI.

PURPOSE: The aim of this study was to assess and compare the sensitivity of power Doppler sonography, contrast-enhanced sonography, plain computed tomography (CT), and dynamic magnetic resonance imaging (MRI) for detecting hepatocellular carcinoma (HCC) nodules incompletely treated with transcatheter arterial embolization (TAE). METHODS: A total of 63 unresectable HCC nodules were examined in this study. The HCCs were treated with TAE. All patients underwent plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI 1 week after TAE. The sensitivity of each modality to incompletely treated HCC nodules was compared. Detection of the residual viable HCC on angiography or tumor biopsy was regarded as the gold standard for the diagnosis of incomplete treatment. RESULTS: Twenty-four nodules (38%) were diagnosed as incompletely treated. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these incompletely treated nodules were 42% (10/24), 46% (11/24), 88% (21/24), and 79% (19/24), respectively. Eighty percent (19 nodules) of the 24 incompletely treated nodules were located within a depth of less than 8 cm. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these superficial incompletely treated nodules were 37% (7/19), 53% (10/19), 100% (19/19), and 74% (14/19), respectively. In contrast, the sensitivities of each modality to deeply located nodules were 60% (3/5), 20% (1/5), 40% (2/5), and 100% (5/5), respectively. CONCLUSION: Plain CT and power Doppler sonography had a low sensitivity to HCC nodules incompletely treated with TAE. Except for those that were deeply located, contrast-enhanced harmonic sonography showed the highest sensitivity in detecting incompletely treated HCC nodules.

[A case of stomach cancer in which TS-1 neoadjuvant therapy was effective against multiple hepatic metastasis, allowing a radical cure A surgery].

It is believed that multiple hepatic metastases from stomach cancer are highly refractory, and resistant to clinical treatment. In the present study, TS-1 neoadjuvant therapy administered orally in a single course brought about CR in the hepatic metastatic foci and PR in the primary foci, thus enabling grade A radical extirpation in a case of advanced stomach cancer. The patient continued to be treated on an ambulatory basis. His peri- and post-operative courses were satisfactory and the treatment was completed without the development of adverse effects.